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PATIENTS AND METHODS
PMC10417045
Patient eligibility
NSCLC
ONCOLOGY, DISEASE, RECURRENCE, NSCLC
Patients with histologically or cytologically confirmed non‐squamous NSCLC with measurable disease were enrolled. Other eligibility criteria included: Stage IIIB (without indications for radical chest radiation therapy), Stage IV, or postoperative recurrence; age ≥20 and <75 years; Eastern Cooperative Oncology Group (E...
PMC10417045
Study design and treatment
toxicities, proteinuria, hemoptysis, Cancer
ONCOLOGY, THORACIC, S; HEMOGLOBIN, CANCER
Patients received induction chemotherapy of cisplatin (75 mg/mThe criteria to start maintenance therapy included: PS 0 or 1; neutrophil count ≥1500/μL; hemoglobin ≥8.0 g/dL; platelet count ≥7.5 × 10Administration of maintenance therapies was suspended if any of the following occurred: neutrophil count <1500/μL; platele...
PMC10417045
Assessment of treatment
tumor, Tumor, SD, Tumors, Toxicity
ADVERSE EVENT, TUMOR, METASTASIS, TUMOR, TUMORS, ADVERSE EVENT
Before commencement of therapy, a complete medical history, physical examination, and resting 12‐lead electrocardiogram were performed. Tumor staging was determined by physical examination, routine chest radiography, computed tomography (CT) of the chest and abdomen, bone scintigraphy, or positron emission tomography (...
PMC10417045
Statistical analysis
NSCLC, SD
ADVERSE EVENTS, ADENOCARCINOMA, NSCLC, EVENTS, PATHOLOGY
The primary endpoint of this study was progression‐free survival (PFS) from randomization. Secondary endpoints were the objective response rate (ORR), overall survival (OS) from randomization, and adverse events. The sample size was calculated with a one‐sided significance level of 0.05 and 80% statistical power using ...
PMC10417045
Analysis of circulating immunocytes of peripheral blood
Circulating immunocytes, such as MDSCs, cluster of differentiation (CD) 4 T‐cells, CD8 T‐cells, and Tregs, were analyzed. To analyze circulating immunocytes, peripheral blood samples of patients were collected at four points (before and after induction chemotherapy, 4–8 weeks after the start of maintenance treatment, a...
PMC10417045
RESULTS
PMC10417045
Patients' characteristics and treatment administration
NSCLC
LUNG CANCER, DISEASE, NSCLC
A total of 108 patients were entered into this study between June 2013 and March 2019. Patients were recruited at 19 investigational sites of TORG in Japan. The patients' characteristics are listed in Table Patients' background characteristics.Abbreviations: NSCLC, non‐small cell lung cancer; NOS, not otherwise specifi...
PMC10417045
Antitumor activity
PD
ADVERSE EVENTS, DISEASE
Of the 108 eligible patients who received induction chemotherapy, 101 were assessable for response to chemotherapy. Seven patients could not be assessed for response because of discontinuation during induction therapy. The reasons for discontinuation during induction therapy were: patients' refusal, four patients; adve...
PMC10417045
Adverse events
hemorrhage, Proteinuria, hypertension
PROTEINURIA, ADVERSE EVENTS, ADVERSE EVENT, HEMORRHAGE, HYPERTENSION
Grade 3 and 4 hematological adverse events in all cycles of maintenance therapy of all 70 patients are listed in Table Adverse events (Grade 3 or 4) during maintenance therapy.Abbreviation: AST, aspartate aminotransferase; ALT, alanine aminotransferase.Proteinuria, hemorrhage from some organs, and hypertension are gene...
PMC10417045
Analysis of circulating immunocytes of peripheral blood
PD
Circulating immunocytes, such as MDSCs, CD 4 T‐cells, CD8 T‐cells, and Tregs, were analyzed. To analyze circulating immunocytes, peripheral blood samples were collected in ten patients. Eight of the ten patients were from the PBgroup and two of the ten patients were from the Pgroup. The eight patients in the PBgroup we...
PMC10417045
DISCUSSION
NSCLC, toxicities, human venous blood samples, tumor
TUMOR, NSCLC
A randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in untreated advanced non‐squamous, NSCLC was conducted. To the best of our knowledge, this is the first study to demonstrate the significant progression free survival benefit ...
PMC10417045
AUTHOR CONTRIBUTIONS
PMC10417045
FUNDING INFORMATION
This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.
PMC10417045
CONFLICT OF INTEREST STATEMENT
The authors have declared no conflicts of interest.
PMC10417045
ACKNOWLEDGMENTS
The authors would like to thank the patients and their families for consenting to participate in the study.
PMC10417045
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
PMC10417045
REFERENCES
PMC10417045
Subject terms
psychotic symptoms, impaired delayed verbal recall
SYNDROME, POSITIVE
As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated...
PMC10156730
Introduction
psychotic symptoms
ADVERSE EFFECTS
Several countries and US states have decriminalised or legalised cannabis use, and many permit the use of cannabis preparations for medicinal purposes. Over a similar period, the potency of cannabis, as indexed by its ∆9-tetrahydrocannabinol (THC) content, has been progressively increasing [As well as THC, cannabis als...
PMC10156730
Methods
The study was approved by the King’s College London Research Ethics Committee (RESCMR-16/17-4163). All participants provided written informed consent and the study was conducted in compliance with the principles of Good Clinical Practice, the Declaration of Helsinki (1996). The study was registered on Open Science Fram...
PMC10156730
Design
CRF
CRF, APPENDIX
This randomised, double-blind, four-arm, within-subjects study was conducted at the NIHR Wellcome Trust Clinical Research Facility (CRF) at King’s College Hospital, London, UK (randomisation and masking described in Appendix 
PMC10156730
Participants
DISORDER, APPENDIX
Forty-six healthy volunteers (age 21–50 years), who had used cannabis at least once in the past, but had not used cannabis >1/week over the last 12 months, had never used synthetic cannabinoids, and did not have a substance use disorder were recruited. Additional inclusion/exclusion criteria are listed in Appendix 
PMC10156730
Procedure (Fig. 
At baseline, participants were assessed for study eligibility, and practiced the inhalation procedure. At baseline and all experimental visits, urine drug and pregnancy screen as well as alcohol and carbon monoxide breath tests (<10 ppm CO to verify 12 h tobacco abstinence) were completed. Participants were asked to av...
PMC10156730
Study drug and administration
The study drug was provided in the form of granulated cannabis inflorescence by Bedrocan BV (Netherlands) produced in accordance with Good Manufacturing Practice and confirms to the European Medicines Agency’s contaminant levels for products used in the respiratory tract. Each cannabis dose consisted of 10 mg of THC (t...
PMC10156730
Blood collection and analysis
Venous blood samples were taken before drug administration, and at 0, 5, 15, and 90 min following the final exhalation, alongside blood pressure, heart rate and temperature. The concentration of Δ9-THC, 11-OH-Δ9-THC (OH-THC), 11-COOH-Δ9-THC (COOH-THC), CBD and 7-OH-CBD were determined using high performance LC/MS at th...
PMC10156730
Cognitive tasks
PMC10156730
Hopkins verbal learning task—Revised (HVLT-R) [
A researcher read out a list of 12 words to the participant, who then repeated the list back. This was repeated over three trials, with the total number of words recalled indexing immediate recall. 20–25 min later participants were asked to recall the words again, indexing delayed recall. The percentage of correctly re...
PMC10156730
Forward and reverse digit span
Digit span is a measure of verbal working memory and attention, involving the recall of sequences of numbers with increasing length (WAIS-III). Beginning with three digits on forward and two digits on reverse, the task ceased when the participant failed two consecutive attempts at a number sequence.
PMC10156730
Spatial N-back [
Participants responded to a visual stimulus appearing in one of eight locations, with task demand varied across 0-back, 1-back, and 2-back conditions. Participants were required to indicate (by pressing a Yes or No button) whether the stimulus appeared at the 12 o’clock position (0-back), the same position as the previ...
PMC10156730
Psychological measures
PMC10156730
Positive and negative syndrome scale—positive subscale (PANSS-P) [
hyperactivity, grandiosity, hallucinations, delusions, suspiciousness, psychotic symptoms, hostility
The PANSS-P is an investigator-rated semi-structured interview, which assesses positive psychotic symptoms (delusions, conceptual disorganisation, hallucinations, hyperactivity, grandiosity, suspiciousness, and hostility). Information from this assessment was supplemented by the researcher’s observations of, and intera...
PMC10156730
State social paranoia scale (SSPS) [
The SSPS was used to assess persecutory thoughts.
PMC10156730
Community assessment of Psychic Experiences—state (CAPE-state) [
The CAPE-state is a self-rated scale and was used to assess psychotic-like experiences.
PMC10156730
Psychotomimetic states inventory (PSI) [
The PSI questionnaire was used to assess psychotic-like experiences following the use of cannabis use.
PMC10156730
Visual analogue scales (VAS)
VAS were used to measure subjective effects along a continuum. Participants marked on a 100 mm horizontal line to indicate the level of a given feeling at that moment (0 mm ‘Not at all’ to 100 mm ‘Extremely’). The feeling states included:
PMC10156730
Pleasurable responses
Pleasurable effects of cannabis were assessed by the participant rating their enjoyment of a piece of either milk (Marabou) or dark (Lindt 70%) chocolate, and a self-selected piece of music, on a visual analogue scale (VAS), ranging from −5 to +5 on a 100 mm line. The centre of the line (indicated by 0) indicates that ...
PMC10156730
Statistical analysis
psychotic-like reactions
According to our power calculation, at 80% power and Bonferroni adjusted alpha <0.008, a sample size of The effect of THC was determined by comparing outcome scores from the baseline visit with those following administration with THC alone (0:1) using paired t-tests. For the primary analysis, we used linear mixed model...
PMC10156730
Results
PMC10156730
Participants and demographics
80 potential participants were screened from which 64 were randomised and 46 completed the study (Fig. Study flow diagram.Demographics and cannabis use at baseline.
PMC10156730
Pharmacokinetics
There were no significant differences in either peak plasma THC, OH-THC or COOH-THC, or their respective AUCs between the CBD:THC ratios (
PMC10156730
Blood plasma THC and CBD concentrations over time and across CBD:THC ratio.
Plasma concentrations of
PMC10156730
Cognitive effects
PMC10156730
Hopkins verbal learning task
When the 0:1 condition (THC only) was compared to baseline, there were impairments in both immediate (t(45) = 5.580,
PMC10156730
Digit span
There was significant impairment in the 0:1 condition compared to baseline in forward digit span (t(45) = 3.309,
PMC10156730
Spatial N-Back
There were no significant differences between baseline and 0:1, or between CBD:THC ratios (
PMC10156730
Psychological effects
PMC10156730
PANSS positive subscale
There was a significant increase in PANSS positive score between baseline and 0:1 (t(45) = −4.709,
PMC10156730
SSPS
There were no significant differences in SSPS scores between baseline and 0:1, between CBD:THC ratios (t(45) = −1.096,
PMC10156730
CAPE
There was a significant increase in total CAPE score between baseline and 0:1 (t(45) = −4.088,
PMC10156730
PSI
There was a significant increase in total PSI score between baseline and 0:1 (t(39) = −7.461,
PMC10156730
VAS
There were no significant differences in subjective effects between CBD:THC ratios in terms of either VAS AUC or peak VAS ratings (
PMC10156730
Pleasurable responses
All CBD:THC ratios increased scores for both chocolate and music compared to baseline, but there were no significant differences between the CBD:THC ratios (
PMC10156730
Physiological effects
PMC10156730
Blood pressure
There were no significant differences in systolic (t(44) = −1.19,
PMC10156730
Heart rate
There was a significant increase in heart rate in the 0:1 condition compared to baseline (t(44) = −9.35,
PMC10156730
Body temperature
APPENDIX
There were no significant differences in body temperature between any of the conditions (Appendix 
PMC10156730
Inhalation and coughing
APPENDIX
There was evidence of greater CBD:THC ratios increasing inhalation time and coughing in a dose responsive manner (Appendix 
PMC10156730
Order and sex effects
fatigue
APPENDIX
Adding order to the models did not have any impact on the significance or direction of pharmacokinetic, cognitive, psychological, subjective, pleasurable, or physiological effects. Restricting the analysis of the primary outcome to visit 1 found no differences across conditions, suggesting no evidence for significant p...
PMC10156730
Discussion
psychotic symptoms, cognitive impairments
Our main finding is that the co-administration of CBD with THC had no effect on the induction of either cognitive impairments or psychotic symptoms following cannabis use. Similarly, CBD did not influence the subjective (as measured by VAS) or the pleasurable effects (music and chocolate) of THC. This was true across t...
PMC10156730
Conclusions
ADVERSE EFFECTS
At the doses typically present in recreational and medicinal cannabis, we found no evidence of CBD reducing the acute adverse effects of THC on cognition and mental health. Similarly, there was no evidence that it altered the subjective or pleasurable effects of THC. These results suggest that the CBD content in cannab...
PMC10156730
Supplementary information
The online version contains supplementary material available at 10.1038/s41386-022-01478-z.
PMC10156730
Acknowledgements
BROWN
We would like to wholeheartedly thank all the participants who took part in this study, both the ones who completed as well as the ones who withdrew. We thank George Brown, John Villajin, Louisa Green, Asha Mathews, Chifundo Stubbs, Olabisi Awogbemila, Noah Yogo, Elka Giemza, Stephanie David, Adebukola Shopade, and Her...
PMC10156730
Author contributions
AE, TF, RM and PMG conceptualised and designed the study, as well as provided continuous review and oversight of the running of the study along with PFP and JS. AE, DO, EC, LC, JW, SS and ADM recruited participants, collected, and interpreted data. JH set up the randomisation algorithm and contributed to the power anal...
PMC10156730
Funding
Maudsley
This study was fully funded by a Research Grant from the Medical Research Council UK (MR/P006841/1). The funder had no involvement in the design, data collection, analysis, interpretation, write up or the decision of where to publish. AE, LC, JH, RMM, and JS are part-funded or supported by the National Institute for He...
PMC10156730
Competing interests
AE has received speakers’ honoraria from GW Pharmaceuticals. RMM has received speakers’ honoraria from Lundbeck, Sunovian, Otsuka, and Janssen. JS has undertaken research supported financially by various pharmaceutical companies, but this has not involved studies of cannabis or cannabis-related products. All remaining ...
PMC10156730
References
PMC10156730
Key Points
PMC10369925
Question
lung cancer, tumor
LUNG CANCER, TUMOR
Can we improve time to treatment using circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced lung cancer?
PMC10369925
Findings
lung cancer, nonsquamous
LUNG CANCER, SMALL CELL LUNG CANCER
In this nonrandomized clinical trial, 150 patients with suspected advanced lung cancer underwent ctDNA testing during initial diagnostic workup; 90 patients had tissue confirmation of advanced nonsquamous non–small cell lung cancer. Median time to treatment was 39 days vs 62 days for a reference cohort, with faster tur...
PMC10369925
Meaning
lung cancer
LUNG CANCER
The use of plasma ctDNA testing before tissue diagnosis among patients with suspected advanced lung cancer may expedite biomarker testing and accelerate time to treatment.
PMC10369925
Importance
NSCLC, tumor
SMALL CELL LUNG CANCER, TUMOR, NSCLC
Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non–small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.
PMC10369925
Objective
NSCLC, tumor
TUMOR, NSCLC
To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.
PMC10369925
Design, Setting, and Participants
lung cancer, Cancer
LUNG CANCER, CANCER
This single-group nonrandomized clinical trial was conducted among 150 patients at the Princess Margaret Cancer Centre–University Health Network (Toronto, Ontario, Canada) between July 1, 2021, and November 30, 2022. Patients referred for investigation and diagnosis of lung cancer were eligible if they had radiologic e...
PMC10369925
Interventions
lung cancer
LUNG CANCER
Patients underwent plasma ctDNA testing with a next-generation sequencing (NGS) assay before lung cancer diagnosis. Diagnostic biopsy and tissue NGS were performed per standard of care.
PMC10369925
Main Outcome and Measures
Accelerating Lung Cancer, nonsquamous NSCLC
The primary end point was time from referral to treatment initiation among patients with advanced nonsquamous NSCLC using ctDNA testing before diagnosis (ACCELERATE [Accelerating Lung Cancer Diagnosis Through Liquid Biopsy] cohort). This cohort was compared with a reference cohort using standard tissue genotyping after...
PMC10369925
Results
nonsquamous NSCLC
Of the 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%]) enrolled, 90 (60%) had advanced nonsquamous NSCLC. The median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort vs 62 days (IQR, 44-82 days) for the reference cohort (
PMC10369925
Conclusions and Relevance
NSCLC
NSCLC
This nonrandomized clinical trial found that the use of plasma ctDNA genotyping before tissue diagnosis among patients with suspected advanced NSCLC was associated with accelerated time to treatment compared with a reference cohort undergoing standard tissue testing.
PMC10369925
Trial Registration
tumor
SMALL CELL LUNG CANCER, TUMOR
ClinicalTrials.gov Identifier: This nonrandomized clinical trial evaluates the use of circulating tumor DNA genotyping before tissue diagnosis among patients with suspected advanced non–small cell lung cancer and its association with time to treatment.
PMC10369925
Introduction
NSCLC, tumor
SMALL CELL LUNG CANCER, TUMOR, NSCLC
Clinical management of newly diagnosed non–small cell lung cancer (NSCLC) requires knowledge of tumor molecular alterations to guide treatment decisions.Liquid biopsies are minimally invasive blood tests that identify circulating tumor DNA (ctDNA) in patients’ plasma.
PMC10369925
Methods
Cancer, Lung Cancer
CANCER, LUNG CANCER
The ACCELERATE (Accelerating Lung Cancer Diagnosis Through Liquid Biopsy) study is a prospective, single-group, minimally invasive nonrandomized clinical trial conducted at the Princess Margaret Cancer Centre–University Health Network (UHN), Toronto, Ontario, Canada. Conduct of this study was approved by the institutio...
PMC10369925
Patients
NSCLC, cancer, lung cancer, unresectable stage III or IV lung cancer, pleural effusions, MCC, malignant disease
LUNG, CANCER, DISEASE, MCC, LUNG CANCER, PLEURAL EFFUSIONS, NSCLC, MALIGNANT DISEASE
Between July 1, 2021, and November 30, 2022, 150 patients were enrolled in the ACCELERATE cohort. Patients referred to the UHN Lung Rapid Assessment and Management Program (LungRAMP) were eligible to participate if they had (1) radiologic evidence of unresectable stage III or IV lung cancer; (2) measurable disease with...
PMC10369925
Study Procedures
After eligibility confirmation, patients were invited to participate in the study (
PMC10369925
Plasma ctDNA Testing
Plasma ctDNA testing was performed using InVisionFirst-Lung, a highly sensitive and specific NGS assay targeting 37 genes that has been prospectively validated and demonstrates high concordance with tissue results and high sensitivity and specificity for variants, single-nucleotide variants, fusions, and copy number al...
PMC10369925
Tumor Tissue Molecular Testing
tumor, Trusight Tumor
TUMOR
Reflex molecular testing of tumor tissue was performed per institutional standard of care, including comprehensive NGS (Oncomine Comprehensive Assay, version 3; Thermo Fisher Scientific) (eFigure 1 in For patients in the reference cohort, reflex testing using an NGS assay targeting 15 genes (Trusight Tumor 15 Panel, Il...
PMC10369925
Study End Points
nonsquamous NSCLC, tumor
ONCOLOGY, TUMOR
The primary end point was time to treatment, defined as the time from diagnostic program referral to systemic treatment initiation for patients with advanced nonsquamous NSCLC enrolled in the ACCELERATE cohort using ctDNA genotyping prior to pathologic diagnosis compared with a reference cohort of consecutive patients ...
PMC10369925
Reference Cohort
lung cancer, NSCLC, Cancer
LUNG CANCER, NSCLC, CANCER
The LungRAMP program maintains a prospective database of all patients referred for investigation of suspected lung cancer. A reference cohort of 89 patients with advanced NSCLC diagnosed through LungRAMP and treated at the Princess Margaret Cancer Centre prior to the COVID-19 pandemic (2018-2019) was identified. Demogr...
PMC10369925
Statistical Analysis
nonsquamous NSCLC
Patient characteristics and molecular data are summarized using median, IQR, frequency, and percentage. The nonparametric Wilcoxon-Mann-Whitney test was used to compare time to treatment for patients with advanced nonsquamous NSCLC enrolled in the ACCELERATE cohort and the reference cohort. The Wilcoxon signed rank tes...
PMC10369925
Results
Between July 1, 2021, and November 30, 2022, 150 patients (median age at diagnosis, 68 years [range, 33-91 years]; 80 men [53%] and 70 women [47%]; and 61 patients [41%] were never smokers) were enrolled in the ACCELERATE cohort (
PMC10369925
Baseline Characteristics and Histologic Diagnoses and Stage in the ACCELERATE and Reference Groups
NSCLC, pleural effusion, death, melanoma, liver lesion, plasmacytoma, lung cancer, Hodgkin lymphoma, Lung Cancer
PLEURAL EFFUSION, MELANOMA, UTERINE LEIOMYOSARCOMA, PROSTATE, MESOTHELIOMA, ONCOLOGY, ENDOMETRIAL ADENOCARCINOMA, PLASMACYTOMA, SMALL CELL LUNG CANCER, HODGKIN LYMPHOMA, BONE LESION, LUNG, CARCINOMA OF UNKNOWN PRIMARY, LUNG CANCER, BONE ISLAND, METASTASES, LUNG CANCER, GASTROINTESTINAL NEUROENDOCRINE CARCINOMA, NSCLC, ...
ACCELERATE, Accelerating Lung Cancer Diagnosis Through Liquid Biopsy; ECOG, Eastern Cooperative Oncology Group; NA, not applicable; NOS, not otherwise specified; NSCLC, non–small cell lung cancer.Not documented in the ACCELERATE cohort: ethnicity (n = 24). ECOG performance status and ethnicity were not systematically c...
PMC10369925
Tissue Diagnosis
NSCLC, pleural effusion, nonsquamous, squamous carcinoma
PLEURAL EFFUSION, ATYPICAL CARCINOID TUMOR, DISEASE, NSCLC, SQUAMOUS CARCINOMA
Biopsy-proven NSCLC was demonstrated in 107 patients (71%), although 3 patients were later found to have early-stage disease and underwent surgical resection (benign pleural effusion and bone and liver lesions). Of 104 patients with advanced NSCLC, 90 patients had nonsquamous histologic characteristics, 2 had atypical ...
PMC10369925
NGS Testing in Plasma and Tissue
cancer
CANCER
All participants underwent plasma testing; 115 (77%) had tumor-associated variants detected (Among the 18 patients with other cancer diagnoses, 7 did not have detectable cfDNA in plasma, but 3 had potentially informative results based on cancer type (eTable 3 in Combining plasma and tissue results, 53 of 90 patients (5...
PMC10369925
Time to Treatment
nonsquamous NSCLC
Most patients (72 of 90 [80%]) started systemic therapy for advanced nonsquamous NSCLC. Median time to treatment was 39 days (IQR, 27-52 days) for the ACCELERATE cohort compared with 62 days (IQR, 44-82 days) for the reference cohort (
PMC10369925
NGS Turnaround Time and Wait Times
In the ACCELERATE cohort, the median turnaround time for plasma testing from blood draw to result reporting was 7 days (IQR, 6-9 days) vs 23 days (IQR, 18-28 days) for tissue NGS, measured from tissue biopsy to reporting (In the reference cohort, referred before the COVID-19 pandemic (
PMC10369925
Discussion
NSCLC, cancer, nonsquamous NSCLC, lung cancer
LUNG CANCER, CANCER, NSCLC
In our study, plasma ctDNA testing before diagnosis in the initial diagnostic workup of patients with suspected advanced NSCLC was associated with shorter time to molecular results than tissue testing and shorter median time to treatment compared with a reference cohort using tissue molecular testing only (39 vs 62 day...
PMC10369925
Limitations
lung cancer, cancers, NSCLC
LUNG CANCER, CANCERS, MALIGNANT NEOPLASMS, NSCLC
Our study has limitations, including its single-group prospective design and the fact that it was conducted at a single institution. Despite expert selection of patients with radiologic evidence of advanced lung cancer by a multidisciplinary team, only 70% of patients had biopsy-proven advanced NSCLC, while 30% had oth...
PMC10369925
Conclusions
lung cancer, NSCLC
LUNG CANCER, NSCLC
In this nonrandomized clinical trial, the use of liquid biopsy before lung cancer diagnosis in the initial diagnostic workup of patients with suspected advanced NSCLC was associated with shortened time to treatment and molecular results and yielded a higher rate of detection of actionable alterations. Complementing sta...
PMC10369925
Subject terms
proarrhythmia
ADVERSE EFFECTS, ATRIAL FIBRILLATION (AF)
Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the KIn a phase 2 clinical trial, an inhibitor of the K
PMC10803288
Main
stroke, heart failure, cardiac arrhythmia
STROKE, HEART FAILURE, ATRIAL FIBRILLATION (AF), CARDIAC ARRHYTHMIA
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with reduced quality of life and increased risk of stroke, heart failure and deathThe KThe AF efficacy of K
PMC10803288
Results
PMC10803288