tbuckley/cabot-search huggingface dataset:
Randomized phase IIb clinical trial of continuation or non-continuation with six cycles of temozolomide after the first six cycles of standard first-line treatment in patients with glioblastoma: A Spanish research group in neuro-oncology (GEINO) trial.
Authors: Carmen Balana, Carlos Mesia Barroso, Sonia Del Barco Berron, Estela Pineda Losada, José Muñoz-Langa, Anna Estival, Ramon De las Peñas, Jose Fuster, Miguel J. Gil Gil, L Miguel Navarro, Miriam Alonso, Ana Herrero, María Ángeles Vaz Salgado, Sergi Peralta, Clara Olier, Pedro Pérez-Segura, Marta Covela Rúa, Cristina Carrato, Carolina Sanz, Juan Manuel Sepulveda-Sanchez
Journal: Journal of Clinical Oncology (2019)

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.
Ibrutinib and Venetoclax — Doubling Down on CLL
Authors: Adrian Wiestner
Journal: New England Journal of Medicine (2019)

Chronic lymphocytic leukemia (CLL) is a clonal expansion of mature B cells in blood, bone marrow, and lymphoid tissues that usually manifests as a high lymphocyte count in the circulating blood. Cell expansion is driven by constitutive B-cell receptor signaling and sustained by overexpression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) (Fig. 1A).1,2 Microbial and autoantigens have been implicated in activating B-cell receptor signaling in CLL cells. Furthermore, many types of B-cell receptors that are expressed by CLL cells also bind to epitopes within their structural domains, promoting cell-autonomous signaling. B-cell receptor signaling mainly occurs in lymphoid tissues and . . .
Management of stage I seminomatous germ-cell cancer (SGCC): Results from 4 different risk-adapted strategies in a single institution.
Authors: Mariona Riudavets, Georgia Anguera, Daniela Camacho, Aida Bujosa, Raul Terés, Maria Borrell, Pablo Gallardo, Berta Martin, Consolacion Molto, Luis del Carpio, Cristina Martin, Gemma Sancho, Ferran Algaba, Joan Palou, Pablo Maroto
Journal: Journal of Clinical Oncology (2019)

e16047 Background: Management of stage I SGCC depends on pathological findings after orchiectomy. Four risk-adapted strategies were sequentially applied in a single institution during a 24-year (yr) period according to national guidelines. Here, we compare treatment burden and outcomes of each of them. Methods: From 1/1994 to 1/2018, 208 patients with stage I SGCC were prospectively included in 4 cohorts. Those without risk criteria underwent close surveillance. Patients received active treatment as follow: Group 1: 1994-1999, only patients with T &gt; pT1 received 2 cycles of carboplatin (CBDCA AUC7 x2); Group 2: 1999-2003, patients received CBDCA AUC7 x2 if either tumor size &gt; 4cm or rete testis invasion; Group 3 : 2004-2009, CBDCA AUC7 x2 if both tumor size &gt; 4cm and rete testis invasion were present; Group 4 : ≥2010, CBDCA AUC7 x1 if either tumor size &gt; 4cm or rete testis invasion. Kaplan Meier and log-rank tests were used to evaluate disease-free survival (DFS), Kruskal-Wallis test to compare amount of chemotherapy received per patient. Results: At a median follow-up of 108 months [range 3-423], 19 (9.1%) relapses had occurred. Global 3 and 5-yr DFS were 92.3% and 90%. All relapsing patients were rendered disease-free with 4 cycles of cisplatin (CDDP) - etoposide. Table 1 summarizes results by cohort: Conclusions: A risk-adapted program provided an overall specific survival of 100%. A clinically significant difference in RR was observed when 1 or 2 courses of CBDCA were given. In our series and considering treatment burden, vascular invasion was a better criteria for patient selection to adjuvant chemotherapy, showing a similar DFS but a lower no of total platinum cycles per patient.[Table: see text]
Experiences of general practitioners and medical specialists with incurable cancer patients with a protracted disease trajectory: A focus group study.
Authors: Hilde M. Buiting, Femke Botman, Lilly-Ann van der Velden, Linda Brom, Florien van Heest, Pieter de Mol, Ton Bakker
Journal: Journal of Clinical Oncology (2019)

e23010 Background: Advances in oncology have resulted in prolonged disease trajectories in patients with incurable cancer. In this disease-phase, patients are aware that cancer is incurable but they do not approach the last phase-of-life yet. We examined experiences and wishes of GPs and specialists concerning appropriate care-provision, delivered by GPs. Methods: We performed 6 focus groups in different regions in the Netherlands; 3 homogenous groups (N=15 GPs) and 3 heterogenous groups (N=23 GPs and medical specialists). Data were analysed with thematic content-analysis. Results: During the first focus-groups, the protracted disease phase was not acknowledged as a separate one; in the last focus-groups, however, this disease-phase received more attention. Physicians clearly distinghuished this trajectory from the palliative / terminal disease phase, partly because many patients did not experience severe physical problems. Most GPs preferred to be involved in the care of these patients as this would enable them to easily guide patients in their last phase-of-life. In these patients, GPs experienced difficulties in estimation of prognosis and advice of further treatment, partly because of insecurity of treatment side-effects of immunotherapy. Further, many physicians experienced difficulties in labeling this disease phase. ‘Stable’; ‘chronic’; and ‘Phase X’ were regularly mentioned. Medical specialists were more frequent involved with these patients but preferred to involve GPs as much as possible. They however also realised that this would become more difficult in future, given the growing group of patients in this disease phase. Conclusions: In the protracted disease phase, patients often do not experience severe physical symptoms. They often do not approach their patient for possible psycho-social problems. Apart from medical specialists, tools to easily communicate across specialties to optimise care need to be further explored.
Safety profile of INT230-6, a novel intratumoral (IT) formulation, during injections into a variety of refractory deep and superficial tumors with evidence of tumor regression and immune activation.
Authors: Anthony B. El-Khoueiry, Jacob Stephen Thomas, Diana L. Hanna, Lillian L. Siu, Nilofer Saba Azad, Giles Francis Whalen, Lewis H. Bender, Ian B. Walters, Anthony J. Olszanski
Journal: Journal of Clinical Oncology (2019)

2602 Background: INT230-6 is comprised of cisplatin (CIS), vinblastine (VIN) and an amphiphilic penetration enhancer which facilitates dispersion throughout tumors and diffusion into cancer cells. In preclinical experiments, INT230-6 led to necrosis and recruitment of immune cells with high rates of complete responses of injected and bystander tumors. This abstract highlights the safety and early pharmacodynamic activity of this approach. Methods: Patients with solid tumors that progressed on all standard treatments were enrolled. Dose escalation occurred by increasing number of tumors injected, loading per tumor, and total dose. INT230-6 was injected once every 2 weeks in multiple lesions for 5 sessions. Patients were monitored for safety and tolerability weekly. Pharmacokinetic(Pk) samples and peripheral blood were collected for flow cytometry and circulating cytokines. Pre and on study biopsies are ongoing. Results: 28 patients (14 unique cancer types) receiving a median of 3 prior treatments were enrolled. Doses from 0.3 ml up to-80 ml of INT230-6 were given into single lesions with some patients receiving a total of 120 mL ( = 9.7mg VIN exceeding the IV VIN dose) without significant systemic absorption or typical cytotoxic adverse events. Pk analysis suggests that systemic exposure of VIN or CIS is ~10% of injected. No DLT’s or drug-related SAE’s reported. The most frequent adverse event was grade 1 or 2 pain at injected site. Superficial tumors showed signs of response including flattening, areas of necrosis and ulceration. Tumor reduction, apparent in in both injected and bystander tumors, may indicate an abscopal effect. An increase &gt; 30% in CD8 T-cells was seen in the blood of 3/9 evaluable patients. Conclusions: INT230-6 was safe and well tolerated in &gt; 100 injections (28 patients) with encouraging activity and pharmacodynamic effects in advanced refractory tumors. Additional analysis of immune cells from on study biopsies will be presented. A new cohort will evaluate combination with an anti-PD1 antibody to understand if local tumor destruction can increase systemic antigen load, increase immune cell recognition and initiate a systemic immune response. Clinical trial information: NCT 03058289.
Abstract O.37: Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings In Kawasaki Disease
Authors: Soha Rached-d'Astous, Ibtissama Boukas, Anne Fournier, Marie-Josée Raboisson, Nagib Dahdah
Journal: Circulation (2015)

Background: Coronary artery dilatations are almost always secondary to Kawasaki disease in the pediatric population. The presence of CA involvement is used as a criterion to diagnose incomplete KD disease, which may be challenging. It has been recently demonstrated that febrile patients had larger CA size than non-febrile children in a pilot study. As there is almost always a myocarditis in the acute phase of KD disease we sought to investigate whether viral myocarditis may cause CA dilatations. Method: This retrospective study reviewed 14 consecutive patients with a diagnosis of viral myocarditis at Saint-Justine Hospital, Montreal, from April 2000 trough December 2010. Kawasaki disease was excluded in all patients. All echocardiogram studies were reviewed by an independent experienced technician for CA size and function parameters. Patients were classified in three categories: definite CA dilatation (Z-score ≥ 2.5 in one or more CA), occult CA dilatation (Z score variation ≥ 2 for the same CA on 2 different echogrardiograms, but absolute Z score always &lt; 2.5) and normal coronary artery. Demographics, laboratory values, microbial etiology testing, diagnostic studies were also collected. Results: Mean age at presentation was 1.67 ± 3.22 years, the majority &lt; 2 years old, and 11 (78%) were girls. Of the 14 patients 8 (57.1%) had normal CA, 3 (21.4%) had occult CA dilatation and 3 (21.4%) had definite CA dilatation. When present, CA dilatation was detected within the first 8 days of presentation. Eleven (78%) patients presented with acute onset features and the remaining 3 presented with subacute characteristics. There was no correlation between CA involvement and the intensity of LV dysfunction however (p = 0.84). Conclusion: Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when diagnosing patients with incomplete KD on the basis of the CA involvement as the two illnesses may present with similar features.
APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant <i>nab</i>-paclitaxel plus gemcitabine (<i>nab</i>-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.
Authors: Margaret A. Tempero, Michele Reni, Hanno Riess, Uwe Pelzer, Eileen Mary O'Reilly, Jordan Michael Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Josep Tabernero, Eric Van Cutsem, Philip Agop Philip, David Goldstein, Jordan Berlin, Stefano Ferrara, Mingyu Li, Brian D. Lu, Andrew Biankin
Journal: Journal of Clinical Oncology (2019)

4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy &amp; safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, &amp; CA19-9 &lt; 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), &amp; geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m 2 + G 1000 mg/m 2 or G 1000 mg/m 2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data &amp; scans. Secondary endpoints were OS &amp; safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), &amp; R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic &amp; nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) &amp; fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.
Molecular comparison between peritoneal metastases (PM) and primary gastric (GC) and gastroesophageal junction (GEJ) cancer.
Authors: Matthew K Stein, Joanne Xiu, Michael Gary Martin, Axel Grothey, Philippe Prouet, Jeffrey Owsley, Forrest W Williard, Evan Scott Glazer, Paxton Vandiver Dickson, David Shibata, Danny Yakoub, Richard M. Goldberg, W. Michael Korn, Anthony Frank Shields, Jimmy J. Hwang, Heinz-Josef Lenz, Jeremiah Lee Deneve
Journal: Journal of Clinical Oncology (2019)

4053 Background: PM from GC or GEJ portend a poor prognosis and molecular differences are ill defined. Methods: We compared genomic profiles of primary (P) GC and GEJ with PM patients (pts) and other metastases (OM) sent to Caris Life Sciences. Testing comprised immunohistochemistry (IHC) including programmed death ligand 1 (PD-L1) combined positive score (CPS), copy number alterations (CNA), 592-gene next-generation sequencing (NGS), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: 1366 cases were identified: 1041 GC (707 P, 98 PM, 236 OM) and 325 GEJ (248 P, 5 PM, 72 OM). PM were increased in GC versus GEJ (9% v. 2%, p &lt; 0.0001). 91% GC and 93% GEJ were adenocarcinoma (AD); GC were more likely signet ring (SR) histology versus GEJ (11% v. 3%, p &lt; 0.0001) and GC PM were more likely SR versus other OM or P (13% v. 12% v. 7%, p = 0.067). The mean age of PM pts (57 years) was younger than primary GC (63, p = 0.002) and OM (61; p = 0.044). More PM GC pts were female than P or OM (48% v. 35% v. 34%, p = 0.03). No molecular profiling differences were seen between GEJ and GC pts and they were combined for analysis; findings from 1246 AD pts are shown below (see Table). OM (9%, p = 0.041) had more CNA in CCNE1 than PM (2%, p = 0.041) or P (5%, p = 0.002). Conclusions: Compared to P and OM GC, PM pts were younger, more likely female and had a higher incidence of SR histology. PD-L1, HER2 IHC and ERBB2 CNA were reduced in PM versus P, suggesting novel therapeutic targets are needed. [Table: see text]
Harnessing digital technology to predict, diagnose, monitor, and develop treatments for brain disorders
Authors: Clare Stroud, Jukka-Pekka Onnela, Husseini Manji
Journal: npj Digital Medicine (2019)

Abstract Digital technologies—including smartphones, wearables, and social media data—show great potential for helping to alleviate suffering from brain disorders such as Parkinson’s disease, Alzheimer’s disease, depression, and schizophrenia. However, as researchers, technology developers, disease-focused groups, and others forge forward to take advantage of the tremendous opportunities in this domain, it is important to avoid hype and overpromising, and to ensure that this work is done rigorously and collaboratively. In June 2018, the National Academies of Sciences, Engineering, and Medicine’s Forum on Neuroscience and Nervous System Disorders hosted a workshop that brought together a wide range of experts and stakeholders. The workshop provided an opportunity to take stock of the rapidly-evolving landscape and discuss how to work together to address both scientific and practical challenges, so that the potential of digital technologies can be translated into meaningful contributions toward the health of individuals and society. Workshop presentations and discussions focused on four key challenges: transforming data into insight, navigating regulatory pathways, designing user-centered tools, and building partnerships across a complex ecosystem. This article highlights the many issues, challenges, and opportunities discussed by individual participants at the workshop.
Flu vaccination rate of patients with severe immune-related adverse events.
Authors: Ian Matthew Allen, Yonina Robbie Murciano-Goroff, Leyre Zubiri, Qun Li, Michael Sang Hughes, Marko Velimirovic, Jacqueline N. Chu, Sienna Durbin, Matthew J Klauer, Magid Awadalla, Laura A Petrillo, Michael Dougan, Alyssa R Letourneau, Michael Mansour, Tomas G. Neilan, Justine Vanessa Cohen, Aditya Bardia, Kerry Lynn Reynolds
Journal: Journal of Clinical Oncology (2019)

e18234 Background: Infection with influenza in adults with cancer carries an increased risk of morbidity and mortality. Vaccination against seasonal influenza (Flu-V) can decrease the incidence of influenza, shorten its course, and reduce influenza-associated morbidity. Recent data has suggested that the administration of the Flu-V to patients on an ICI leads to an exaggerated inflammatory response and an increased risk of irAE. However, this trend was demonstrated in a small cohort of patients with lung cancer. Current recommendation for annual Flu-V in patients treated with ICI is unclear and literature about safety is limited. We compared rates of Flu-V for patients on ICI admitted with severe toxicity vs those patients on ICI who were admitted for reasons other than toxicity. We also evaluated rate of Flu-V among oncology patients who had received non-immunotherapy modalities. Methods: We retrospectively evaluated patients treated with ICI who were admitted to Massachusetts General Hospital from February 5, 2011- June 12, 2017. Patients received ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or a combination in treatment of an advanced solid tumor malignancies including melanoma, NSCLC, SCCHN. Admissions due to irAE were confirmed by review of clinical, radiologic, and pathologic features. Flu-V status was determined by rigorous chart review. Nearest neighbor matching was used to create a control group of cancer patients treated with non-ICI modalities. Descriptive statistics compared rates and timing of Flu-V relative to admission. Statistical significance was determined using Fischer’s Exact Test, p &lt; 0.05. Results: Of 540 patients on ICI, 28% were admitted for irAE, 72% had a non-irAE reason for admission. The rate of Flu-V in the flu season prior to admission for irAE group was lower than for non-irAE (18.5% vs 29.6%; p value = 0.01). There were no differences in vaccination rates within ≤30 days (2.7% vs 3.6%, p = 0.80), ≤90 days (4.0% vs 9.3%, p = 0.05), or ≤180 days of admission (11.9% vs 18.5%, p = 0.07). Flu-V rate overall in patients on ICI was 26.5%. In comparison, Flu-V rate in the nearest neighbor non-immunotherapy oncology patients was 67% (n = 101). Conclusions: Flu-V rates were much lower in patients treated with ICI compared to patients treated with non-ICI modalities. We did not see a higher rate of Flu-V in patients admitted with irAE compared to non-irAE which suggests that Flu-V and severe irAE may not be linked in clinical practice. Additional studies are needed, but Flu-V in patients on ICI holds potential to improve care.
Predicting Outcomes of High-Flow Nasal Cannula for Acute Respiratory Distress Syndrome. An Index that ROX
Authors: Nicholas S. Hill, Robin Ruthazer
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

maintenance oral corticosteroid therapy, and alternative therapeutic approaches might be best, although these are limited for those with no evidence of eosinophilic inflammation.How can this precision medicine approach be further improved, particularly for those with no evidence of eosinophilic inflammation, to find new treatments?Differential analysis of the omics data characterizing each of these four clusters may provide clues to the pathways that may underlie corticosteroid responsiveness.The other approach would be to first cluster on available transcriptomic or proteomic data.Taking this approach in the U-BIOPRED (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes project) cohort, Kuo and colleagues clustered transcriptomic pathways associated with inflammatory and immune mechanisms in bronchial biopsies and epithelial cells using machine learning to obtain T2-high molecular phenotypes associated with corticosteroid insensitivity (11).With use of an inference scheme, these molecular clusters could be predicted by using the inflammatory biomarkers of sputum eosinophilia and FE NO levels, together with oral corticosteroid use, with good sensitivity and specificity.The work of Wu and colleagues emphasizes the need for the unsupervised approach and the application of machine learning techniques that can provide useful tools for the clinician while improving understanding of corticosteroid insensitivity in severe asthma.