scholarly journals MO29-2 Osimertinib for RT-naïve CNS metastasis of EGFRm NSCLC: pll OCEAN study (LOGIK 1603/WJOG 9116L), part of T790M cohort

2021 ◽  
Vol 32 ◽  
pp. S316
Author(s):  
Kenji Chibana ◽  
Hiroyuki Yamaguchi ◽  
Kazushige Wakuda ◽  
Minoru Fukuda ◽  
Hirotsugu Kenmotsu ◽  
...  
Keyword(s):  
Cns Metastasis ◽  
Ocean Study

A phase II study of osimertinib for patients with radiotherapy-naïve CNS metastasis of non-small cell lung cancer harboring EGFR mutations: The OCEAN study (LOGIK 1603/WJOG 9116L).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9597-9597
Author(s):  
Kazushige Wakuda ◽  
Hiroyuki Yamaguchi ◽  
Hirotsugu Kenmotsu ◽  
Minoru Fukuda ◽  
Noriyuki Ebi ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Response Rate ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Cns Metastasis ◽  
Ocean Study ◽  
Egfr T790m

9597 Background: Approximately 15%–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression. Although radiotherapy is a standard treatment for CNS metastasis, the efficacy of radiotherapy against CNS is poor. The aim of OCEAN study was to assess the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of NSCLC harboring EGFR mutations. Methods: OCEAN study was two-cohort phase II trial, 65 patients (T790M cohort; 40 patients and first-line cohort; 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive NSCLC was included. Patients were treated with osimertinib 80 mg once daily. The primary endpoint was the response rate of brain metastasis (BMRR) assessed by the PAREXEL criteria. We set a threshold value of 50% and an expected value of 70% based on the overall response rate (ORR) of AURA trial. Based on one-sided alpha = 0.05 and power = 0.8, the sample size of T790M cohort was calculated to be 40. Key secondary endpoints were progression-free survival (PFS), and ORR, BMRR assessed by the RECIST criteria. We are exploratorily assessing the blood concentration of osimertinib at day 22, which considered to represent steady state. In this report, we present the results of T790M cohort. Results: Between October 2016 to July 2019, 40 participants were recruited in the T790M cohort. The median age was 66.5 with 30.0% male. Eight patients had symptomatic CNS metastasis and most patient had multiple CNS metastasis (77.5%). BMRR assessed by PAREXEL criteria was 66.7% (95%CI: 54.3 – 79.1%) and BMRR assessed by RECIST was 70.0% (95%CI, 49.9 – 90.1%). Median PFS was 7.1 months (95%CI, 3.4 – 13.6 months) and ORR assessed by RECIST was 40.5% (95%CI, 24.7 – 57.9%). Treatment related pneumonitis was observed in 4 patients (10.0%). There was no grade 3 or higher toxicities that were found in more than 10%. Conclusions: This first study assessed the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of EGFR T790M mutation-positive NSCLC. The OCEAN study met primary endpoint. The results of this study suggested that patients with brain metastasis harboring EGFR T790M mutations had better to receive osimertinib prior to brain radiotherapy. Clinical trial information: 071180017 .

Tectonic structure and evolution of the southern part of the Central sector of the Indian ocean

2020 ◽  
pp. 3-11
Author(s):  
E. P. Dubinin ◽  
A. V. Kokhan ◽  
G. L. Leitchenkov ◽  
A. A. Shaikhullina
Keyword(s):  
Indian Ocean ◽  
Oceanic Crust ◽  
Geophysical Data ◽  
Digital Models ◽  
Tectonic Structure ◽  
Ocean Study ◽  
The Indian Ocean

The article is dedicated to review of structural and evolutionary peculiarities of the southern part of central sector of the Indian ocean. Study is based on analyses of global digital models, distribution of fractures, global and regional lithosphere evolution models and published geological and geophysical data. As a result of study, tectonic regionalization of oceanic crust of the area is presented and main evolution stages of the region are distinguished.

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

scholarly journals On the chemical dynamics of extracellular polysaccharides in the high Arctic surface microlayer

Ocean Science ◽  
2012 ◽  
Vol 8 (4) ◽  
pp. 401-418 ◽  
Author(s):  
Q. Gao ◽  
C. Leck ◽  
C. Rauschenberg ◽  
P. A. Matrai
Keyword(s):  
Molecular Weight ◽  
Organic Matter ◽  
Compositional Analysis ◽  
Physicochemical Characteristics ◽  
High Arctic ◽  
The Arctic ◽  
Extracellular Polysaccharides ◽  
Surface Microlayer ◽  
Biological Origin ◽  
Ocean Study

Abstract. The surface microlayer (SML) represents a unique system of which the physicochemical characteristics may differ from those of the underlying subsurface seawater (SSW). Within the Arctic pack ice area, the SML has been characterized as enriched in small colloids of biological origin, resulting from extracellular polymeric secretions (EPS). During the Arctic Summer Cloud Ocean Study (ASCOS) in August 2008, particulate organic matter (POM, with size range > 0.22 μm) and dissolved organic matter (DOM, < 0.22 μm, obtained after filtration) samples were collected and chemically characterized from the SML and the corresponding SSW at an open lead centered at 87.5° N and 5° E. Total organic carbon was persistently enriched in the SML with a mean enrichment factor (EF) of 1.45 ± 0.41, whereas sporadic depletions of dissolved carbohydrates and amino acids were observed. Monosaccharide compositional analysis reveals that EPS in the Arctic lead was formed mainly of distinctive heteropolysaccharides, enriched in xylose, fucose and glucose. The mean concentrations of total hydrolysable neutral sugars in SSW were 94.9 ± 37.5 nM in high molecular weight (HMW) DOM (> 5 kDa) and 64.4 ± 14.5 nM in POM. The enrichment of polysaccharides in the SML appeared to be a common feature, with EFs ranging from 1.7 to 7.0 for particulate polysaccharides and 3.5 to 12.1 for polysaccharides in the HMW DOM fraction. A calculated monosaccharide yield suggests that polymers in the HMW DOM fraction were scavenged, without substantial degradation, into the SML. Bubble scavenging experiments showed that newly aggregated particles could be formed abiotically by coagulation of low molecular weight nanometer-sized gels. Aerosol particles, artificially generated by bubbling experiments, were enriched in polysaccharides by factors of 22–70, relative to the source seawater. We propose that bubble scavenging of surface-active polysaccharides could be one of the possible mechanisms for the enrichment of polysaccharides in the high Arctic open lead SML.

scholarly journals OTHR-04. Gynecological Malignancies With Metastasis To The Central Nervous System: A Case Series and Systematic Review of the Literature

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii15-iii15
Author(s):  
Azeem Sajjad ◽  
Adeleso Adesina ◽  
Penelope Halkiadakis ◽  
Kelsey Murphy ◽  
Kathleen Mulligan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Literature Review ◽  
Metastatic Disease ◽  
Case Series ◽  
Progression Free Survival ◽  
Gynecologic Malignancies ◽  
Free Survival ◽  
Cns Metastasis

Abstract Introduction Gynecologic malignancies are an increasingly common proportion of central nervous system metastatic disease. As genetic sequencing technology improves and becomes more accessible, mutations associated with CNS metastasis are easier to elucidate. The aims of this case series and systematic literature review are to describe the patient population with CNS metastatic disease from a gynecologic primary, and to investigate why the proportion of CNS metastasis from gynecologic malignancies is increasing. Ultimately, we hope to improve understanding of this subset of metastatic CNS malignancies and improve management strategies. Methods A literature review of articles describing patients from 1990–2020 who were diagnosed with CNS metastasis from a known gynecologic primary malignancy was performed. Demographics, cancer type, mutation characteristics, management for metastatic disease, progression free survival, number of CNS metastases, and location of metastatic disease were assessed. Inclusion criteria were age&gt;18 years, diagnosis of primary ovarian, uterine, or cervical cancer with confirmed metastatic disease to the CNS, including brain parenchyma, leptomeninges, or intradural spinal cord or dural metastases. Exclusion criteria included pediatric population and bony metastases (e.g., bony spine metastases without evidence of meningeal/parenchymal invasion). Results Our review showed that patients with gynecological metastasis to the CNS generally have worse outcomes regarding overall survival, progression free survival, and quality of life than patients without CNS metastasis. Discussion Our results infer that the reported increase in incidence of CNS metastasis from gynecologic malignancies is a reflection of improvement of detection given advances in technology, improved patient follow up, and increased overall survival of patients with gynecologic malignancies. Further characterization of mutations from gynecologic malignancies associated with brain metastasis could result in development of more treatment options for patients in the future and help determine factors that contribute to developing metastasis to the CNS of various degrees, thus, potentially inform treatment strategies.

NIMG-07. BEYOND RANDOM AND NUMERIC LESIONS: DIFFERENT IMAGING PATTERNS OF CENTRAL NERVOUS SYSTEM METASTASIS BASED ON PRIMARY TUMOR LOCATION AND MOLECULAR PROFILE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi128-vi128
Author(s):  
Júlia Magalhães ◽  
Raquel Moreno ◽  
Jorge Takahashi ◽  
Leandro Lucato ◽  
Carlos Silva
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Molecular Profile ◽  
Imaging Findings ◽  
Central Nervous System Metastasis ◽  
Cns Metastasis ◽  
Imaging Characteristics

Abstract The purpose of this exhibit is to discuss different imaging patterns of central nervous system (CNS) metastasis based on their primary cancer site and to review the recent literature of the particularities of CNS metastasis distribution in the era of molecular advancement in oncology. Selected cases extracted from our institutions database will be presented. The cases will be didactically organized to illustrate the most common imaging characteristics and distribution of brain metastasis based on their organ of origin, such as lung, breast, renal, skin, testicle and gastrointestinal tract. (SCHROEDER T. et al., J Neurooncol. 2020). We will also discuss the correlation between tumor imaging findings and genetic profile. We intend to review well-known CNS metastasis imaging patterns, as preferential involvement of the posterior fossa and anatomic watershed areas in cases of lung cancer (TAKANO, K. et al. Neuro-Oncology, 2016) and the rarity of parenchyma metastasis from prostate cancer (HATZOGLOU V. et al, J Neuroimaging. 2014). We will also demonstrate newly described imaging findings in correlation with primary tumors genetic mutations, such as higher incidence of leptomeningeal involvement in triple negative breast cancer and increase in the number of brain lesions in cases of EGFR positive lung cancer. Familiarity with the most prevalent imaging characteristics of central nervous system metastasis helps oncologists and radiologists not to miss out a CNS progression in case of a known tumor, and also helps to direct systemic investigation of a primary tumor when brain metastasis is the initial presentation. The correlation between molecular profile and the most common sites of CNS involvement can help on treatment planning, including brain radiation (Yanagihara TK,et al., Tomography. 2017), and also bring to discussion the mechanisms of tumor dissemination, which can be targets for future treatments.

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