tbuckley/cabot-search huggingface dataset:
P05.90 A prospective phase II study of whole brain radiotherapy concomitant to Temozolomide in primary central nervous system lymphoma after high dose methotrexate
Authors: F Catucci, S Chiesa, E Maiolo, M Giraffa, F Beghella Bartoli, T Zinicola, S Hohaus, M Rufini, V Valentini, M Balducci
Journal: Neuro-Oncology (2018)

The purpose of this study is to evaluate the overall survival in patients diagnosed with primary cerebral lymphoma (PCNSL) treated with radiotherapy associated with Temozolomide (TMZ) after treatment with high dose methotrexate (HD-MTX). Patients with an histological diagnosis of PCNSL, receiving HD-MTX, were enrolled to receive Temozolomide concomitant to radiotherapy. The whole brain up to C2 leptomeninges was irradiated by 30 Gy in 15 daily fractions, while the radiation dose to initial or residual disease, if present, was modulated according to the response to HD-MTX (Complete response = 6 Gy, partial response = 10 Gy, progression disease = 16 Gy). Concomitant Temozolomide was administered at a safety dose level of 75 mg/mq according to our previous escalation study. From March 2004 to December 2017 were enrolled 33 patients: 18 males and 15 females. The median age was 64.5 yrs (range 50–76). Twenty two patients received two cycles of HD-MTX, 9 received only one cycle, because of hematological toxicity, and 2 patients did not received any cycle because of poor performance status. Nine patients were subjected to macroscopic surgical excision while the remaining patients were only subjected to biopsy. Twenty-five patients were subjected to radio-chemotherapy with TMZ. The median follow up was 80 months (range 3–169), 9 out of 33 patients (27%) are alive (7 without disease and 2 with stable disease), 22 patients died because of disease and two patients because of other causes. The median survival (OS) of the whole group was 23.1 months with at 1 yrs OS of 64% and at 3 yrs OS of 43%. The concomitant use of TMZ showed a significant impact on OS (P = 0.004). This prospective study demonstrated that the use of TMZ at a dose of 75 mg/mq associated with radiotherapy shows better results in terms of OS than radiotherapy alone.
Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC).
Authors: Johanna C. Bendell, Tae Won Kim, Boon C. Goh, Jeffrey Wallin, Do-Youn Oh, Sae-Won Han, Carrie B. Lee, Matthew David Hellmann, Jayesh Desai, Jeremy Howard Lewin, Benjamin J. Solomon, Laura Quan Man Chow, Wilson H. Miller, Justin F. Gainor, Keith Flaherty, Jeffrey R. Infante, Meghna Das-Thakur, Paul Foster, Edward Cha, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2016)

3502 Background: Atezolizumab (atezo; MPDL3280A) is an engineered antibody that inhibits binding of PD-L1 to its receptors, PD-1 and B7.1. Atezo has demonstrated monotherapy activity in a multitude of human tumor types. However, response rates in microsatellite stable (MSS) CRCs have been lower than in other indications. In preclinical models, targeted inhibition of MEK leads to upregulation of MHC I on tumor cells, induces intratumoral T-cell infiltration and enhances anti-PDL1 activity. We therefore conducted a Phase Ib study combining cobi (MEK inhibitor) and atezo in patients (pts) with advanced solid tumors. Methods: Cobi was escalated from 20 to 60 mg daily (21 days on/7 days off) and combined with atezo 800 mg IV q2w. Tumor-specific expansion cohorts, including KRAS-mutant CRC, and serial biopsy cohorts in solid tumors were opened upon determination of the MTD. Safety, tolerability and confirmed ORR by RECIST v1.1 were evaluated. Results: As of October 12, 2015, 23 CRC (22 KRAS mutant, 1 WT) pts were enrolled during escalation and expansion. No dose-limiting toxicities were observed, and expansion occurred at atezo 800 mg q2w and cobi 60 mg. Median follow-up for safety in CRC pts was 3.78 mo (range, 1.1-11.7). The most common treatment-related AEs included diarrhea (69.6%), fatigue (52.2%), dermatitis acneiform (43.5%), rash (34.8%), maculopapular rash (26.1%), pruritus (26.1%) and nausea (26.1%). Incidence of treatment-related G3-4 AEs was 34.8%. The only treatment-related G3-4 AE in ≥ 2 pts was diarrhea (8.7%). No G5 AEs were reported. The ORR was 17% (4 PR, 5 SD). Three responses were ongoing (range, 4.0 to 7.7 mo at time of data cutoff). Three responders were mismatch repair-proficient, and 1 was unknown. Response was not associated with baseline PD-L1 expression. Results from the serial biopsy cohort showed enhanced PD-L1 upregulation, CD8 T-cell infiltration and MHC I expression on treatment, providing mechanistic rationale for the combination. Conclusions: The combination of cobi and atezo in CRC is well tolerated at the maximum administered doses. These results show that pts with MSS CRC can respond to the combination of cobi and atezo, and provide support for continued evaluation of the combination. Clinical trial information: NCT01988896.
As-needed budesonide–formoterol was noninferior to maintenance budesonide for exacerbations in mild asthma
Authors: Matthew B. Stanbrook
Journal: Annals of Internal Medicine (2018)

ACP Journal Club18 September 2018As-needed budesonide–formoterol was noninferior to maintenance budesonide for exacerbations in mild asthmaMatthew B. Stanbrook, MD, PhDMatthew B. Stanbrook, MD, PhDToronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-6-030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide–formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378:1877-87. https://pubmed.ncbi.nlm.nih.gov/29768147Clinical Impact RatingsGIM/FP/GP: Allerg & Immunol: Pulmonology: References1 Sobieraj DM, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis. JAMA 2018;319:1485-96. [PMID: 29554195] Google Scholar2 Global Initiative for Asthma. Global strategy for asthma management and prevention, 2018. http://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/ (accessed 9 Jul 2018). Google Scholar3 Horne R. Compliance, adherence and concordance: implications for asthma treatment. Chest. 2006;130(1 Suppl):65S-72S. [PMID: 16840369] Google Scholar Author, Article, and Disclosure InformationAffiliations: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)This article was published at Annals.org on 4 September 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAs-needed budesonide–formoterol better controlled mild asthma vs terbutaline, but maintenance budesonide was better Matthew B. Stanbrook As-needed budesonide–formoterol better controlled mild asthma vs terbutaline, but maintenance budesonide was better Matthew B. Stanbrook Metrics 18 September 2018Volume 169, Issue 6Page: JC30KeywordsAdverse eventsAsthmaBronchodilatorsClinical trialsHazard ratioInflammationLungsMedical risk factorsPatientsPulmonary medicine ePublished: 18 September 2018 Issue Published: 18 September 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
An evaluation of the microbiota of the upper genital tract of women with benign changes and epithelial ovarian cancer.
Authors: Wendy R. Brewster, Emily Meichun Ko, Temitope O Keku
Journal: Journal of Clinical Oncology (2016)

5568 Background: The microbiota of the upper female genital tract has not been characterized. We hypothesize that bacterial species composition will vary in different areas and may alter terms of resilience to disturbances. We hypothesize that there are distinct microbiota of the female upper genital tract in women with epithelial cancers of the fallopian tube-ovary compared to women with benign disease. Methods: Postmenopausal women scheduled for hysterectomy and salpingo-oophorectomy were prospectively identified. Women who used antibiotics during the three months prior to hysterectomy were excluded, as were those with a known diagnosis of cancer of the uterus or cervix. Bacteria were extracted from tissue samples of the proximal fallopian tube, the fimbrea and the ovarian surface.Using molecular-phylogenetic methods based on the highly conserved 16S bacteria rRNA gene we assessed the complexity of upper genital tract microbiota in tissue samples by sequencing the V1-V2 region of the 16S gene on the Ion Torrent platform. Sequences were processed through QIIME and an average of 69,625 reads per sample was obtained after quality filtering. Multivariate analyses were conducted using PRIMER VI software. Results: The initial analysis of 25 samples from the proximal fallopian tube, fimbriae and ovary suggest that bacteria exist in the upper reproductive tract of postmenopausal women. The global R statistic suggests that the bacterial composition in the upper reproductive tract is different for the areas examined (p = 0.005). The bacterial composition is significantly different between the fallopian tube and ovary (p = 0.008). The proximal fallopian tube bacteria composition also differs from the fimbriated end (p = 0.01). When analyzed by epithelial ovarian cancer status, there is evidence of two groups with borderline differences in microbial profiles of cancer vs. no cancer (p = 0.06) Conclusions: We identified distinct microbiota of the female upper genital tract and a profile unique to women with epithelial ovarian cancer. Further investigation is necessary to determine if changes in the microbiota may precede the development of and contribute to fallopian tube-ovarian cancer susceptibility.
Genomic profiling of carcinomas of unknown primary (CUP) to support clinical decisions.
Authors: Alwin Krämer, Ferran Losa, Laurie M. Gay, Ethan Sokol, Damian R. Page, Garrett Michael Frampton, Stefan Foser, Tariq I. Mughal, Jeffrey S. Ross, Giulia Baciarello, Linda R. Mileshkin, Holger Moch
Journal: Journal of Clinical Oncology (2018)

e24162 Background: CUP represents a wide range of heterogeneous tumors with diverse genomic alterations (GAs) and high unmet clinical need. Molecular profiling of gene panels at diagnosis is increasingly used to support clinical decisions. Methods: Formalin-fixed, paraffin-embedded sections from 4650 patients (pts) > 18y diagnosed with advanced CUP (3058 adenocarcinomas [ACUP], 1592 carcinomas not otherwise specified [UCUP]) were sequenced with a hybridization-capture, adaptor ligation-based comprehensive genomic profiling assay to a mean depth of > 500X for 315 cancer-related genes. Total mutational burden (TMB) and microsatellite instability (MSI) were determined on 1.1 Mb of sequenced DNA. Mutational profiles were analyzed to characterize associations between clinical phenotype, signaling pathways, and candidacy for molecularly targeted therapies (TTs) or immune checkpoint inhibitors (ICPIs) for those with high MSI or TMB (≥16 mutations/Mb). Results: Median age of the cohort was 63y (range 19–88); 52% were female. Median GAs/sample was 3; 3675 (79%; ACUP = 2486, UCUP = 1189) harbored ≥1 GA/biomarker relevant for TT/ICPI; an additional 485 (10%; ACUP = 280, UCUP = 205) had GAs associated only with an investigational TT. 1767 (36%) unique samples harbored a GA specific for 8 common TT/ICPI strategies, with 275 (6%) having a profile relevant to > 1 strategy (Table, some samples counted > once if relevant for > 1 therapy; n = 1912). Of 554 (12%) samples with high TMB/MSI, 145 (26%) harbored a GA in MDM2, STK11, or JAK1/2, known/suspected to reduce ICPI sensitivity. Conclusions: Our current knowledge-based approach in pts affected by CUP describes informative genomic features that can be assessed in a prospective randomized trial investigating TTs and ICPIs. This information may also offer insights into subtypes of CUP that may be associated with reduced efficacy for some of these therapies. Therapy class Samples relevant to therapy, n (ACUP;UCUP) Samples relevant for other therapy, n ALKi EGFRi HER2i SMOi BRAFi AKTi PARPi anti-PD-L1 ALKi 30 (19;11) - 0 0 1 0 3 1 2 EGFRi 98 (67;31) - 10 0 0 7 4 14 HER2i 329 (248;81) - 3 1 40 19 35 SMOi 48 (19;29) - 2 8 7 21 BRAFi 102 (66;36) - 15 6 9 AKTi 608 (369;239) - 42 91 PARPi 259 (164;95) - 53 anti-PD-L1 438 (232;206) -
Molecular and clinicopathological classification of high risk endometrial cancer (EC) treated with concurrent chemoradiation therapy (CCT).
Authors: Marta Gil-Martin, August Vidal-Bel, Laura Valle, Ana Velasco, Beatriz Pardo, Sabela Recalde, Luz Ventura Zaa, Valentín Navarro-Perez, Rebeca Sanz-Pamplona, Susanna Marin i Borras, Jordi Ponce, Lola Marti, Marc Barahona, Jordi Rovira, Josep M. Piulats, Xavier Matias-Guiu
Journal: Journal of Clinical Oncology (2017)

e17110 Background: Recently, TCGA proposed a molecular classification in EC that might hold prognostic significance. This project aim is to evaluate the outcome of high risk EC treated with CCT and its correlation with a surrogate molecular classification. Methods: A total of 49 patients (pts) treated from 2011 to 2016 were included in a prospective database. Pts were treated with 2 cycles (C) of cisplatin on days 1 and 28 concurrent with external beam radiotherapy (RT) of the pelvis, plus brachytherapy (BCT); followed by 4 C of paclitaxel and carboplatin every 3 weeks. The molecular classification into the 4 groups of TCGA (POLE mut, MSI, CN-low, CN-high/serous-like) has been performed in 38 pts using a surrogate classification that consists in POLE mutations detection by Sanger, and immunohistochemistry for p53 and MMR, as surrogate markers for TP53 mutations and MSI. Results: Pts median age was 67yo; Endometrioid pathology in 59%, serous 20% and others 20%; up to 73% were grade 3; and FIGO Stage III in 82%. All pts received full dose of RT, 80% BCT, and 75% completed 6C of CT. With a median follow-up of 39 months [17-65], 6% of pts experienced local recurrence, and 30% metastatic relapse. 3-year overall survival (OS) and cancer–specific survival (CSS) was 80%, and 3-year progression free survival was 74%. Median OS is not reached at this point. Pts were molecularly classified as: 0% POLE mut, 13% CN-low, 37% MSI and 50% CN-high. Survival data show that CN-low present an 3-y OS and CSS of 100%, MSI of 82% and CN-high of 67%. No statistically significant differences have been found, probably due to the low number of events and pts. It is remarkable the survival difference between endometrioid and serous tumors in the CN-high group (86% vs 50%, respectively). This tendency can be observed in TCGA pts as well. Conclusions: CCT followed by CT is an effective adjuvant therapy in high risk EC pts with an acceptable toxicity. Correlation with molecular prognostic classification has shown a big proportion of patients in the MSI and CN-high groups, known to have worse prognosis. Morphologic differentiation between endometrioid and serous carcinomas in CN-high group might still hold prognostic implications.
Clinical factors influencing engraftment in patients with non-Hodgkin lymphoma following autologous stem cell transplant.
Authors: William Paul Skelton, Forat Lutfi, Yu Wang, Emma Rosenau, Hemant S. Murthy, Randy Brown, John R. Wingard, Maxim Norkin
Journal: Journal of Clinical Oncology (2018)

e19504 Background: Autologous Stem Cell Transplant (ASCT) is considered as standard of care for patients (pts) with relapsed and refractory non-Hodgkin's lymphoma (NHL). In this study we evaluated delayed engraftment (DE) in large cohort of ASCT recipients with NHL. Methods: 1,162 pts undergoing ASCT at a single institution from 1996-2016 were retrospectively reviewed to determine DE, defined as platelet count ≤50,000/μl, hemoglobin ≤8 g/dL, or ANC ≤1000 mm3. Pts with prior ASCT or those lost to follow up were excluded. Results: NHL represented only 209/1162 (18.0%) of pts undergoing ASCT but accounted for 108/239 (45.2%) of pts with DE at 30 days (Table 1). By comparison, multiple myeloma (MM) represented 686/1162 (59.0%) of pts undergoing ASCT but accounted for only 69/239 (28.9%) of pts with DE at 30 days. This was statistically significant (p = 0.05, OR = 2.377 (95% CI 1.00, 5.65). Given this discrepancy for the engraftment of NHL pts, the 108 NHL pts with DE were analyzed further to determine clinical factors influencing development of DE in NHL pts. In univariate analysis NHL type (p = 0.99), stage (p = 0.95), disease status at transplant (p = 0.54), bone marrow or extranodular involvement (p = 0.54, 0.68), conditioning regimen (p = 0.39), EBV and CMV viral serologies (p = 0.51, 0.06), history of radiation therapy (p = 1.0), prior chemotherapy regimens, and CD34+ dose (p = 0.11) showed no statistically significant impact on development of DE in NHL pts. Conclusions: DE was identified in 52% of all pts with NHL and pts with NHL have a significantly higher risk for the development of DE as compared to MM pts. Disease stage, bone marrow or extranodular involvement, chemotherapy regimen, or other treatment related factors had no influence of DE indicating that this inherent characteristic of NHL and its impact of marrow microenvironment can be responsible for this discrepancy in DE Table 1: Demographics of NHL pts with DE Variable n = 108 (%) Stage 1 (1%) 2(14%) 3(17%) 4(69%) NHL subtype - DLBCL 57 (53%) Mantle cell 18 (17%) Follicular 11 (10%) T-cell 10 (9%) B-cell 6 (6%) Other 6 (6%) Disease status at transplant - CR 59 (55%) PR 49 (45%) Extranodular disease - Yes 67 (62%) No 41 (38%) Bone marrow involvement - Yes 40 (37%) No 68 (63%)
Prevalence and short-term outcomes of venous thromboembolism in hospitalized patients with hematologic malignancies: A nationwide analysis.
Authors: Kahee A. Mohammed, Zarir Ahmed, Eric Adjei Boakye, Jiajing Chen, Nosayaba Osazuwa-Peters, Martin W. Schoen, Leslie J. Hinyard, Kevin A Palka
Journal: Journal of Clinical Oncology (2018)

e18728 Background: Patients with hematologic malignancies are at increased risk of venous thromboembolism (VTE) and its complications. This study aimed to investigate the prevalence of VTE and its impact on in-hospital mortality, length of hospital stay, and health care utilization in patients with hematologic malignancies. Methods: Data from Nationwide Inpatient Sample (2008 – 2013) were analyzed to identify hospitalized patients (aged ≥18 years) with hematologic malignancies (n = 518,648). Weighted, multivariate hierarchical logistic regression analyses were performed to adjust for patient and hospital level variation in outcomes. Results: The prevalence of VTE was higher among patients with multiple myeloma (MM) (4.2%), followed by and non-Hodgkin’s Lymphoma (NHL) (4.0%) and Hodgkin’s lymphoma (HL) (3.8%). In the adjusted models, VTE was associated with higher odds of in-hospital mortality across all hematologic malignancies (Table), but it was most notable among patients with NHL (OR = 2.2, 95% CI = 1.9–2.6), HL (OR = 1.9, 95% CI = 1.6–2.4), and chronic lymphocytic leukemia (CML) (OR = 1.9, 95% CI = 1.4–2.5). Patients with VTE were twice as more likely to have a prolonged hospitalization and have double the total hospital charges compared to those without VTE (Table). Conclusions: The prevalence of VTE is high among hospitalized patients with MM and lymphomas and is associated with prolonged hospital stay and significant hospital charges. Strategies for early detection of VTE and prompt management should be targeted to reduce morbidity and healthcare cost. Total Patients Venous Thromboembolism Prevalence In-hospital Mortality aOR (95% CI) Prolonged Hospital Stay aOR (95% CI) Average Total Hospital Charges: VTE v No VTE CLL 99,110 3.3% 1.5 (1.3–1.8) 2.8 (2.5–3.1) $75,067 vs $46,172 CML 28,071 2.4% 1.9 (1.4–2.5) 2.7 (2.1–3.4) $122,465 vs $57,452 AML 82,100 3.2% 1.4 (1.2–1.6) 1.9 (1.8–2.1) $198,219 vs $111,842 ALL 58,338 2.2% 1.3 (1.0–1.7) 1.9 (1.6–2.2) $191,090 vs $75,246 MM 116,751 4.2% 1.3 (1.2–1.5) 2.3 (2.0–2.5) $84,410 vs $56,126 Non-Hodgkin 45,727 4.0% 2.2 (1.9–2.6) 2.2 (1.9–2.6) $106,839 vs $59,993 Hodgkin 33,551 3.8% 1.9 (1.6–2.4) 2.5 (2.1–3.0) $100,161 vs $54,432
Abstract 13596: Magnetic Resonance - Derived Pre-contrast T1 Relaxation Time is the Accurate Marker of Diffuse Myocardial Fibrosis in Severe Aortic Valve Disease: A Comparison With Left Ventricular Myocardial Biopsy
Authors: Radka Kockova, Petr Kacer, Jan Pirk, Jiri Maly, Martina Vsianska, Lucie Sukupova, Viktor Sikula, Martin Kotrc, Alena Praveckova, Lucia Barciakova, Eva Honsova, Marek Maly, Josef Kautzner, Vojtech Melenovsky, David Sedmera, Martin Penicka
Journal: Circulation (2015)

Introduction: Diffuse myocardial fibrosis (DFM) is the major mechanism in the pathophysiology of the aortic stenosis and its complications. DMF is detectable by magnetic resonance imaging (MRI) using the T1 mapping technique. Hypothesis: The MRI derived native T1 relaxation time and myocardial extracellular volume fraction (ECV) will be significantly related to the extent of DMF et targeted myocardial left ventricular (LV) biopsy. Methods: The study population consisted of 40 consecutive patients (age 63±8y, 65% males) undergoing surgery for severe aortic stenosis (77.5%), aortic root dilatation (7.5%) or valve regurgitation (15%). All patients underwent MRI-derived T1 mapping and 2D-, 3D speckle tracking-derived strain analysis prior to surgery. The T1 relaxation time was assessed in basal interventricular septum pre and 10 min post contrast administration using the modified Look-Locker Inversion recovery sequence. A LV myocardial biopsy specimen was obtained during surgery from basal interventricular septum under the guidance of the MRI operator to assure spatial concordance with the MRI assessment. The percentage of myocardial collagen was quantified as a ratio of Picrosirius Red-positive area over total sample area using the Image J. Results: The average percentage of myocardial collagen was 22 ± 14.8 %. The average native T1 relaxation time and ECV was 1010 ± 48 ms and 0.288 ± 0.055, respectively. Both native T1 relaxation time with cutoff value of ≥ 1010 ms (Ss=90%, Sp=73%, AUC =0.82) and ECV with cutoff value of ≥ 0.315 (Ss=80%, Sp=90%, AUC =0.85) showed high accuracy to identify extensive (&gt; 30%) myocardial collagen content (Figure 1A, 1B). The native T1 mapping showed significant correlation with LV mass, 2D and 3D global longitudinal strain (all p&lt;0.05) while the ECV did not (p=NS). Conclusions: Native T1 relaxation time is the accurate marker of diffuse myocardial fibrosis with the significant relationship with LV morphology and myocardial function.