Predicting early relapse in patients with BRAFV600E melanoma with a highly sensitive blood BRAF assay.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8516-8516 ◽  
Author(s):  
Ryan J. Sullivan ◽  
Donald P. Lawrence ◽  
Keith T. Flaherty ◽  
David F. McDermott ◽  
Julie Aldridge ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Stage Iv ◽  
Peripheral Blood Lymphocytes ◽  
Response To Therapy ◽  
Highly Sensitive ◽  
Pre Treatment ◽  
Time Of Presentation ◽  
To Receive ◽  
Further Development ◽  
Braf Mutant

8516 Background: Many patients (pts) with metastatic melanoma (MM) who progress on BRAF inhibitors (BRAFi) develop rapidly progressive disease (PD) which is difficult to manage. Identification of an early marker of PD may allow for therapeutic intervention prior to clinical deterioration. We have developed a highly sensitive and inexpensive assay in our laboratory which can detect as little as 1 BRAFV600E mutant melanoma cell in 400,000 peripheral blood lymphocytes (PBL). We aimed to determine the utility of our assay as a tool to follow pts with BRAF mutant MM who are being treated with a BRAFi. Methods: Every pt had a BRAFV600E mutation detected from a tumor sample in a CLIA-approved laboratory prior to commencing BRAFi therapy. 20 pts with stage IV BRAFV600E MM underwent serial venopunctures before and every 4 weeks during treatment with a BRAFi. BRAFV600E level was quantified using our proprietary assay (Panka et al Melanoma Research 2010). Serial BRAFV600E levels were generated for every pt and normalized to the pre-treatment value. BRAFV600E level was then correlated with response to therapy and PD. Results: BRAFV600E was detected in the PBL of each pt. To date, 10 pts have had BRAFV600E levels quantified at 3 or more time points (data for all 20 pts will be available at time of presentation). Relative BRAFV600E levels reduced by half following the first and second cycles of treatment in 7 pts, which correlated with disease regression in each pt. Following the third cycle of treatment, the relative BRAFV600E levels varied greatly with a subset of pts having continued suppression while others having a rise in their BRAFV600E levels. In each pt with PD, the BRAF assay showed an increase > 4 wks in advance of clinically or radiographically defined PD. Conclusions: Our assay is able to quantify changes in BRAFV600E levels in the blood of pts with BRAF mutant MM receiving BRAFi therapy. In these pts, the BRAFV600E levels are reduced in the setting of initial disease regression and increase well in advance of clinical or radiographic PD. While further development is necessary, such a test could be used to identify pts who may be selected to receive alternative therapy prior to clinical or radiographic PD.

Impact of Temperature on Injection-Related Pain Caused by Subcutaneous Administration of Ustekinumab: A Three-arm Crossover Open-label Randomized Controlled Trial

2017 ◽  
Vol 1 (3) ◽  
pp. 117-127
Author(s):  
Yasaman Mansouri ◽  
Yasmin Amir ◽  
Michelle Min ◽  
Raveena Khanna ◽  
Ruiqi Huang ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Subcutaneous Administration ◽  
Open Label ◽  
Post Dose ◽  
Subcutaneous Injections ◽  
Pain Scores ◽  
Observational Cohort ◽  
Vas Scores ◽  
Pre Treatment ◽  
To Receive

Background: Adherence to subcutaneous biologic agents for the treatment of psoriasis can be negatively influenced by injection pain.Objective: To explore the differences in injection site pain when patients are pre-treated with heat or cold, versus no pre-treatment prior to administration of a subcutaneous biologic agent.Methods: In an observational cohort study, patients receiving subcutaneous injections of ustekinumab were randomly assigned to receive pretreatment with ice, heat, or no intervention over three visits. Post-dose, patients rated pain on a 100 mm visual analogue scale (VAS).Results: There was an increase in the VAS score for both heat (2.51, P=0.30) and ice (3.33, P=0.16), compared to no intervention. No differences were found between the two intervention groups (-0.83, P=0.73). On average, females had the same VAS scores with ice compared to that of no intervention (-0.12, P=0.97) and a non–significant decrease of 3.29 points (P=0.38) with heat. Males had increased pain scores by 5.65 points (P=0.07) with ice and by 6.39 points (P=0.04) with heat.Limitations: Pain is a subjective measurement and objective quantification is difficult.Conclusions: On average, neither heat nor cold application reliably reduced pain. Our results do not support the application of heat or cold prior to ustekinumab injection.

scholarly journals Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 169-174
Author(s):  
Lei Lei ◽  
Liu Yang ◽  
Yang-yang Xu ◽  
Hua-fei Chen ◽  
Ping Zhan ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Clinical Features ◽  
Survival Benefit ◽  
Stage Iv ◽  
Primary Lesion ◽  
Hepatoid Adenocarcinoma ◽  
Seer Database ◽  
Primary Tumor Size ◽  
Adenocarcinoma Of The Lung ◽  
To Receive

Abstract Hepatoid adenocarcinoma of the lung (HAL) is a rare malignant tumor that is defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. We aimed to identify prognostic factors associated with the survival of patients with HAL using data from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients diagnosed with HAL, adenocarcinoma (ADC), and squamous cell carcinoma (SCC) of the lung between 1975 and 2016 from the SEER database. The clinical features of patients with ADC and SCC of the lung were also analyzed. The clinical features of HALs were compared to ADCs and SCCs. A chi-square test was used to calculate the correlations between categorical variables, and a t test or Mann–Whitney U test was used for continuous variables. The Kaplan–Meier method and Cox regression analysis were used to identify the prognostic factors for the overall survival (OS) of HALs. Two-tailed p values < 0.05 were considered statistically significant. Sixty-five patients with HAL, 2,84,379 patients with ADC, and 1,86,494 with SCC were identified from the SEER database. Fewer males, advanced stages, and more chemotherapy-treated HALs were found. Compared to patients with SCC, patients with HAL were less likely to be male, more likely to be in an advanced stage, and more likely to receive chemotherapy (p < 0.05). The American Joint Committee on Cancer staging was the only prognostic factor for OS in patients with HAL, and stage IV was significantly different from other stages (hazard ratio = 0.045, 95% confidence interval: 0.005–0.398, p = 0.005). Males with HAL were more likely to receive radiotherapy compared to females with HAL (61.8 vs 31.5%, p = 0.034). Younger patients with HAL were more likely to receive chemotherapy (59.4 + 10.2 years vs 69 + 11.3 years, p = 0.001). The primary tumor size of HAL was associated with the location of the primary lesion (p = 0.012). No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL (p > 0.05). This study showed that stage IV was the only prognostic factor for OS in HALs compared to other clinicopathologic factors. Conventional antitumor therapies failed to show survival benefit; thus, a more effective method by which to treat HAL is needed. Interestingly, the clinical features and the location of the primary lesion were shown to be associated with primary tumor size and treatment in patients with HAL, which have not been reported before.

scholarly journals Mass Spectrometry versus Conventional Techniques of Protein Detection: Zika Virus NS3 Protease Activity towards Cellular Proteins

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3732
Author(s):  
Agnieszka Dabrowska ◽  
Aleksandra Milewska ◽  
Joanna Ner-Kluza ◽  
Piotr Suder ◽  
Krzysztof Pyrc
Keyword(s):  
Mass Spectrometry ◽  
Zika Virus ◽  
Viral Infections ◽  
Protein Detection ◽  
Extensive Discussion ◽  
Protein Targets ◽  
Highly Sensitive ◽  
Infected Cells ◽  
Ns3 Protease ◽  
To Receive

Mass spectrometry (MS) used in proteomic approaches is able to detect hundreds of proteins in a single assay. Although undeniable high analytical power of MS, data acquired sometimes lead to confusing results, especially during a search of very selective, unique interactions in complex biological matrices. Here, we would like to show an example of such confusing data, providing an extensive discussion on the observed phenomenon. Our investigations focus on the interaction between the Zika virus NS3 protease, which is essential for virus replication. This enzyme is known for helping to remodel the microenvironment of the infected cells. Several reports show that this protease can process cellular substrates and thereby modify cellular pathways that are important for the virus. Herein, we explored some of the targets of NS3, clearly shown by proteomic techniques, as processed during infection. Unfortunately, we could not confirm the biological relevance of protein targets for viral infections detected by MS. Thus, although mass spectrometry is highly sensitive and useful in many instances, also being able to show directions where cell/virus interaction occurs, we believe that deep recognition of their biological role is essential to receive complete insight into the investigated process.

scholarly journals Hepatocellular Carcinoma Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE): Outcome Analysis Using a Model Based On Pre-Treatment CT Texture Features

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 956
Author(s):  
Marcello Andrea Tipaldi ◽  
Edoardo Ronconi ◽  
Elena Lucertini ◽  
Miltiadis Krokidis ◽  
Marta Zerunian ◽  
...  
Keyword(s):  
Texture Analysis ◽  
Clinical Data ◽  
Transarterial Chemoembolization ◽  
Prognostic Value ◽  
Texture Features ◽  
Response To Therapy ◽  
Survival Prediction ◽  
Ct Examination ◽  
Drug Eluting ◽  
Pre Treatment

(1) Introduction and Aim: The aim of this study is to investigate the prognostic value, in terms of response and survival, of CT-based radiomics features for patients with HCC undergoing drug-eluting beads transarterial chemoembolization (DEB-TACE). (2) Materials and Methods: Pre-treatment CT examinations of 50 patients with HCC, treated with DEB-TACE were manually segmented to obtain the tumor volumetric region of interest, extracting radiomics features with TexRAD. Response to therapy evaluation was performed basing on post-procedural CT examination compared to pre-procedural CT, using modified RECIST criteria for HCC. The prognostic value of texture analysis was evaluated, investigating the correlation between radiomics features, response to therapy and overall survival. Three models based on texture and clinical variables and a combination of them were finally built; (3) Results: Entropy, skewness, MPP and kurtosis showed a significant correlation with complete response (CR) to TACE (all p < 0.001). A predictive model to identify patients with a high and low probability of CR was evaluated with an ROC curve, with an AUC of 0.733 (p < 0.001). The three models built for survival prediction yielded an HR of 2.19 (95% CI: 2.03–2.35) using texture features, of 1.7 (95% CI: 1.54–1.9) using clinical data and of 4.61 (95% CI: 4.24–5.01) combining both radiomics and clinical data (all p < 0.0001). (4) Conclusion: Texture analysis based on pre-treatment CT examination is associated with response to therapy and survival in patients with HCC undergoing DEB-TACE, especially if combined with clinical data.

scholarly journals Antimalarial Activity of the Myxobacterial Macrolide Chlorotonil A

2014 ◽  
Vol 58 (11) ◽  
pp. 6378-6384 ◽  
Author(s):  
Jana Held ◽  
Tamirat Gebru ◽  
Markus Kalesse ◽  
Rolf Jansen ◽  
Klaus Gerth ◽  
...  
Keyword(s):  
Screening Program ◽  
Antimalarial Activity ◽  
Stage Iv ◽  
Short Exposure ◽  
Parasite Development ◽  
Content Type ◽  
Highly Active ◽  
New Antibiotics ◽  
Further Development ◽  
Antimalarial Action

ABSTRACTMyxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylumProteobacteria. They are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. In the course of a bioactivity screening program of secondary metabolites produced bySorangium cellulosumstrains, the macrolide chlorotonil A was found to exhibit promising antimalarial activity. Subsequently, we evaluated chlorotonil A againstPlasmodium falciparumlaboratory strains and clinical isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory concentration between 4 and 32 nM; additionally, no correlations between the activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho, −0.046) were observed.Per ostreatment ofPlasmodium berghei-infected mice with four doses of as little as 36 mg of chlorotonil A per kg of body weight led to the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A acts against all stages of intraerythrocytic parasite development, including ring-stage parasites and stage IV to V gametocytes, and it requires only a very short exposure to the parasite to exert its antimalarial action. Conclusively, chlorotonil A has an exceptional and unprecedented profile of action and represents an urgently required novel antimalarial chemical scaffold. Therefore, we propose it as a lead structure for further development as an antimalarial chemotherapeutic.

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Primary Analysis ◽  
Open Label ◽  
Secondary Endpoints ◽  
To Receive ◽  
Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

scholarly journals Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors

2021 ◽  
Author(s):  
Luis E. Raez ◽  
Kathleen Danenberg ◽  
Daniel Sumarriva ◽  
Joshua Usher ◽  
Jacob Sands ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Response To Therapy ◽  
Liquid Biopsies ◽  
Blood Samples ◽  
Lung Cancers ◽  
Metastatic Lung ◽  
Clinical Responses ◽  
Pre Treatment ◽  
Actin Expression

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

scholarly journals Development of a Flexible, Extendable, and Low-Cost Control Unit for Surface Drifters

2017 ◽  
Vol 34 (3) ◽  
pp. 669-677
Author(s):  
Andrea Giudici ◽  
Tomas Torsvik ◽  
Tarmo Soomere
Keyword(s):  
Mobile Communications ◽  
Low Cost ◽  
Control Unit ◽  
Digital Data ◽  
Operational Testing ◽  
Small Footprint ◽  
Surface Drifters ◽  
Inland Water Bodies ◽  
To Receive ◽  
Further Development

AbstractAn extensible, low-cost drifter control unit (VELELLA) design is presented, developed for use in drifters that are deployed in inland water bodies or near-coast regions. The control unit is custom built from basic components built around a small footprint microcontroller, making use of a GPS receiver for position tracking, a Global System for Mobile Communications [Groupe SpécialMobile (GSM)] radio for data transmission, and two sensor buses to handle analog and digital data generated by an arbitrary array of external sensors. A cloud-based data collection platform has been implemented to receive and store data transmitted over general packet radio service (GPRS) from the drifter. The control unit was found to perform satisfactorily in operational testing, providing data at subhertz frequency for position and temperature during extended time. However, some issues related to temporary data loss and power consumption spikes were identified, indicating that some further development of the control unit is required to achieve a production-ready platform for extensive and prolonged field operations.

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