scholarly journals 917 Immune landscape at the invasion front of surgically resected oral squamous cell carcinomas shows significant associations with disease specific survival

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A962-A962
Author(s):  
Jebrane Bouaoud ◽  
Frank Rojas Alvarez ◽  
Lucas Michon ◽  
Nicolas Gadot ◽  
Sylvie Lantuejoul ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Stroma ◽  
Squamous Cell Carcinomas ◽  
Institutional Review Board ◽  
P Value ◽  
Invasion Front ◽  
Institutional Review ◽  
Cell Phenotypes ◽  
Written Informed Consent ◽  
Disease Specific

BackgroundOral squamous cell carcinomas (OSCC) prognosis remains poor. While AJCC TNM 8th edition has slightly improved patients‘ stratification with regard to prognostic, innovative approaches to are still needed. As in other tumor types, tumor immune microenvironment (TiME) might represent an opportunity to improve prognostic assessment.MethodsTiME landscape of 47 HPV-negative OSCC was analyzed using multiplex immunofluorescence (mIF). Markers for tumor cells (PanCK), tumor infiltrating lymphocytes (CD3, CD8), macrophages (CD68), inhibitory (PD-1, PD-L1, TIM3, LAG3, VISTA) or stimulatory (OX40, ICOS) immune checkpoints (ICP) were studied. Regions of interest (ROI), 5 in the tumor core and 5 at the invasion front, were subjected to cell markers identification and quantification (scoring) as well as tissue compartmentalization to divide them in tumor-epithelial and tumor-stroma compartments, respectively. A total of 20 cell phenotypes were defined based on previous work (CK+, CK+PD-L1+, CD3+, CD3+CD8+, CD3+PD-1+, CD3+CD8+PD-1+, CD3+PD-L1+, CD3+CD8+PD-L1+, CD3+PD-L1+PD-1+, CD3+CD8+PD-L1+PD-1+, CD68+, CD68+PD-L1+, CK+OX40+, CD3+VISTA+, CD3+ICOS+, CD3+LAG3+, CD3+OX-40+, CD3+TIM3+). Results were correlated with clinical features including disease-specific survival (DSS) using the Kaplan-Meier method and a multivariate Cox model. A multivariate general linear model (GLM) was built to test the specific association of each variable with a given cell density by correcting the possible confusion due to other variables.ResultsImmune cells densities were significantly higher overall in the stroma. The intra-tumor stroma showed a significant enrichment of in CD3+PD-1+ T cells compared to peri-tumor stroma. None of the clinical or pathological (resection margin, tumor stage, lymph node invasion, perineural invasion) was significantly associated with DSS. In contrast, the following cell phenotypes in the tumor invasion front were strongly associated with a poor DSS, including CD3+PD-L1+ (P-value= 0.004), CD3+PD1+PD-L1+ (P-value= 0.02) and CD3+OX40+ (P-value= 0.02) T cells as well as CD3+CD8+PD-1+ (P-value= 0.048), CD3+CD8+PD-L1+ (P-value= 0.008) and CD3+CD8+PD1+PD-L1+ (P-value= 0.01) cytotoxic T cells. In the tumor core, CD68+PD-L1- macrophages (P-value= 0.06) were marginally associated with better DSS. Using a GLM, we found that tumor from smoker-drinker patients and/or with pN+, were significantly more infiltrated by PD-1- and/or PD-L1-positive immune cells. On the other hand, floor of mouth and gingiva-mandibular OSCC were significantly less infiltrated than others.ConclusionsThe prognostic value of PD-1+ and/or PD-L1+ cells in the invasion front of resected OSCC was remarkable, underlying the importance of this area when studying the TiME. Incorporating TiME analysis in the invasion front may improve prognostic evaluation of patients treated for OSCC, especially in the context of immunotherapy.AcknowledgementsThis study was supported by a strategic alliance between the Translational Molecular Pathology-Immunoprofiling las (TMP-IL) at the Department Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center and the Université Claude Bernard Lyon, Centre de Recherche en Cancérologie de Lyon and the Department of Translational Medicine, Centre Léon Bérard, Lyon, France. The authors would acknowledge ITMO Cancer 2020, ”Formation à la Recherche Fondamentale et Translationnelle en Cancérologie” (JB); CLARA 2020 ”Soutien à la mobilité des jeunes chercheurs en oncologie, N° CVPPRCAN000198” (JB); Fondation de France 2020 ”Aide à la mobilité international de médecins et pharmaciens, N° 00112162” (JB); Ligue contre le cancer 2021, comité de Saône-et-Loire (PS); 2017-INCa-DGOS-Inserm_12563: INCa SIRIC-LYriCAN INCa-DGOS-Inserm_12563 (PS)Ethics ApprovalThe study was conducted in accordance with all applicable laws, rules, and requests of French and European government authorities. Written informed consent was obtained from all patients and the study was approved by the Centre Leon Bérard institutional review board (Lyon, France). Samples were obtained from the CRB Centre Léon Bérard (n°BB-0033-00050) which is quality certified according NFS96-900 French standard and ISO 9001 for clinical trials.ConsentWritten informed consent was obtained from all patients and the study was approved by the Centre Leon Bérard institutional review board (Lyon, France)

scholarly journals 489 TWT-101: a phase 1 study of the novel HPK1 inhibitor CFI-402411 in patients with advanced cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A519-A519
Author(s):  
Omid Hamid ◽  
Johanna Bendell ◽  
Siqing Fu ◽  
Kyriakos Papadopoulos ◽  
Judy Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Research Ethics ◽  
Potent Inhibitor ◽  
Phase 1 ◽  
Institutional Review Board ◽  
Institutional Review ◽  
Research Ethics Board ◽  
Grade 3 ◽  
Advanced Tumors

BackgroundCFI-402411 is an orally available small molecule potent inhibitor of HPK1 (Hematopoietic progenitor kinase 1). T-cells are negatively-regulated at different junctures of cancer-immunity cycle by this regulatory kinase. HPK1, (also mitogen activated protein kinase kinase kinase kinase 1 (MAP4K1)) is a protein serine/threonine kinase predominantly expressed in hematopoietic cells. In T-cells, following T-cell receptor activation, HPK1 is recruited to the plasma membrane where it phosphorylates the adapter protein SH2 domain-containing leukocyte protein of 76 kDa (SLP-76), down-regulating signaling events required for T cell activation and proliferation. Selected for development based on its pharmacologic properties and preclinical activity in a variety of syngeneic cancer models and assays, with an IC50 = 4.0±1.3 nM, CFI-402411 is expected to relieve HPK1-mediated inhibition of T and B cells, facilitating an anti-tumor immune response.MethodsPhase 1, 3 + 3 design in patients. Patients have acceptable laboratory, other parameters for study entry. Single agent dose daily oral escalation cohort (A1) in advanced tumors, then dose expansion (A3) with biomarker backfill (A2) in select advanced tumors; combination with PD-1 Inhibitor (pembrolizumab) (B1, pembrolizumab eligible tumors with no prior grade >=3 related to CPI)) and expansion (B2, PD-1/PD-L1 naïve pembrolizumab eligible tumors). DLT defined as any grade >=3 toxicity in first cycle of therapy (21d cycles). Standard assessments for response per RECIST v1.1 or iRECIST. The starting dose level was 80mg.ResultsAt 10 June 2021 data is available for 12 patients from A1. Median age 61.5 years (range 33–73), 8 patients female, and 10 white. Diagnoses were pancreatic cancer, colorectal (3 pts), ovarian, basal cell, cholangiocarcinoma, sigmoid, salivary and breast cancer (1 pt). Six patients (50%) had 4 prior therapies, 1 patient (basal cell) had prior treatment with immune checkpoint inhibitor, pembrolizumab. Four doses studied: 80, 120, 180 and 270mg. TEAEs across all CTCAE grades, (in >2 patients) were diarrhea (6 patients), nausea (4 patients), dyspepsia (3 patients), fatigue (3 patients). No related grade 3–5 events, one immune related event (grade 1, weight loss). 3 grade 3 events all unrelated to study drug - pleural effusion, rash, thromboembolic event. Discontinuation due to disease progression was main reason (7 patients). PK and PD assessments will be updated at time of presentation.ConclusionsCFI-402411 is a potent inhibitor of HPK1 that is well tolerated with a manageable adverse event profile and dose escalations continue. Further safety and efficacy results will be presented at the meeting including additional cohorts if available.AcknowledgementsTreadwell Therapeutics thanks all sites, importantly their patients and their families.Trial RegistrationClinicalTrials.gov Identifier: NCT04521413Ethics ApprovalThis study obtained has obtained ethics approvals at multiple institutions globally including;USAWCG IRB - Western Institutional Review Board - MOD00002618 (Submission ID)IntegReview Institutional Review Board - N/AAdvarra Central IRB - SSU00130103IntegReview Institutional Review Board N/AAdvarra Central IRB - SSU00137751Advarra Central IRB - SSU00143275The University of Texas MD Anderson Cancer Center Institutional Review Board - 2020–0678 (IRB ID Number)Hong KongJoint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee - 2020.367 (Ref Number)CanadaOntario Cancer Research Ethics Board - 3320 (Project ID)Health Research Ethics Board of Alberta, HREBA Cancer Committee - HREBA.CC-20–0504 (Ethics ID Number)South KoreaimCORE - Seoul National University Hospital Institutional Review Board - H-2012-094-1182 (IRB Number)National Cancer Institute Review Board - 2020–0525–0001 (Receipt Number)All participants gave informed consent before taking part in this clinical trial.

scholarly journals Cannabinoid Disposition in Oral Fluid after Controlled Smoked Cannabis

2012 ◽  
Vol 58 (4) ◽  
pp. 748-756 ◽  
Author(s):  
Dayong Lee ◽  
David M Schwope ◽  
Garry Milman ◽  
Allan J Barnes ◽  
David A Gorelick ◽  
...  
Keyword(s):  
Drug Testing ◽  
Oral Fluid ◽  
Institutional Review Board ◽  
Test Interpretation ◽  
Drug Detection ◽  
Institutional Review ◽  
Cannabis Smoking ◽  
Ad Libitum ◽  
Written Informed Consent ◽  
Median Maximum

Abstract BACKGROUND We measured Δ9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) disposition in oral fluid (OF) following controlled cannabis smoking to evaluate whether monitoring multiple cannabinoids in OF improved OF test interpretation. METHODS Cannabis smokers provided written informed consent for this institutional review board–approved study. OF was collected with the Quantisal™ device following ad libitum smoking of one 6.8% THC cigarette. Cannabinoids were quantified by 2-dimensional GC-MS. We evaluated 8 alternative cutoffs based on different drug testing program needs. RESULTS 10 participants provided 86 OF samples −0.5 h before and 0.25, 0.5, 1, 2, 3, 4, 6, and 22 h after initiation of smoking. Before smoking, OF samples of 4 and 9 participants were positive for THC and THCCOOH, respectively, but none were positive for CBD and CBN. Maximum THC, CBD, and CBN concentrations occurred within 0.5 h, with medians of 644, 30.4, and 49.0 μg/L, respectively. All samples were THC positive at 6 h (2.1–44.4 μg/L), and 4 of 6 were positive at 22 h. CBD and CBN were positive only up to 6 h in 3 (0.6–2.1 μg/L) and 4 (1.0–4.4 μg/L) participants, respectively. The median maximum THCCOOH OF concentration was 115 ng/L, with all samples positive to 6 h (14.8–263 ng/L) and 5 of 6 positive at 22 h. CONCLUSIONS By quantifying multiple cannabinoids and evaluating different analytical cutoffs after controlled cannabis smoking, we determined windows of drug detection, found suggested markers of recent smoking, and minimized the potential for passive contamination.

311 Phase II trial of lymphodepletion plus adoptive cell transfer with or without dendritic cell vaccination in patients with metastatic melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A338-A338
Author(s):  
Chantal Saberian ◽  
Rodabe Amaria ◽  
Cara Haymaker ◽  
Marie Andree Forget ◽  
Roland Bassett ◽  
...  
Keyword(s):  
T Cells ◽  
Metastatic Melanoma ◽  
Phase Ii Trial ◽  
Adoptive Cell Transfer ◽  
Institutional Review Board ◽  
Cancer Center ◽  
Institutional Review ◽  
Significant Difference ◽  
Melanoma Patients ◽  
Md Anderson

BackgroundAdoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has shown great benefit in patients with melanoma.1,2 It was suggested that long term tumor immunosurveillance is provided by TIL persisting after transfer. Dendritic cells (DC) are professional antigen presenting cells and have the ability to optimally activate T lymphocytes.3 We hypothesized that the combination of autologous TIL containing a population of HLA-A0201 restricted MART-1 reactive CD8+ TIL with autologous MART-1 antigen-pulsed DCs will result in enhanced proliferation and prolonged survival of the transferred antigen-specific T cells in vivo, thus leading to improved clinical responses.MethodsThis is a randomized phase II trial of lymphodepleting chemotherapy followed by autologous TILs ± DC vaccine and high dose Interleukin-2 (IL-2) for patients with metastatic melanoma. Patients were randomized to receive TIL alone or TIL + DCs pulsed with MART-1 peptide. The primary objective was to determine whether patients receiving TIL + DCs have sustained persistence of infused T cells compared to patients treated with TIL alone. Secondary endpoints included evaluation of tumor response and survival.ResultsA total of 18 patients with stage IV melanoma were treated; 89% with stage M1c, including 56% with brain metastasis; 17% had high LDH level. All but one patient were checkpoint naïve prior to TIL. Ten patients received TIL alone and eight received TIL + DC. Treatments were well tolerated with no grade 5 adverse events. There were no toxicities conferred by the DC vaccination. The ORR was 63% (5/8) in TIL + DC arm (1 CR, 4 PR) and 40% (4/10) in TIL arm alone (1 CR, 3 PR) (P=0.64). There was no statistically significant difference in survival between the arms. The median progression-free survival (PFS) was 3.6 months in the TIL arm and 7.2 months in the TIL+DC arm, while the median overall survival (OS) was 4.1 years in the TIL arm and 2 years in the TIL+DC arm. Tracking of the infused MART-1 reactive CD8+ T cells in the blood over time by flow cytometry showed no difference in persistence between the two arms.ConclusionsACT with TILs has robust response in checkpoint naïve advanced melanoma patients. Despite numerically higher response rate in the TIL+DC arm, due to small patient number there was no statistically significant difference between the arms. Further testing of this approach in a prospective trial post-ICI is warranted.Trial RegistrationAll metastatic melanoma TIL lines were derived from tumor tissue obtained from patients enrolled on the TIL ACT clinical trial [institutional review board (IRB)-approved protocol# 2004-0069, NCT00338377] at The University of Texas MD Anderson Cancer Center.Ethics ApprovalThe United States Food and Drug Administration and the Institutional Review Board at MD Anderson Cancer Center approved the study. This study was conducted according to the principles from the Declaration of Helsinki.ConsentAll study participants granted a written informed consent prior to treatment initiation.ReferencesRosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015;348(6230):62–8.Forget MA, Haymaker C, Hess KR, Meng YJ, Creasy C, Karpinets T, et al. Prospective Analysis of Adoptive TIL Therapy in Patients with Metastatic Melanoma: Response, Impact of Anti-CTLA4, and Biomarkers to Predict Clinical Outcome. Clin Cancer Res. 2018;24(18):4416–28.Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.

scholarly journals Protocol for a validation study of the translated stapesplasty outcome test 25 for measurement of disease-specific quality of life in Dutch patients with otosclerosis

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e030219
Author(s):  
Esther E Blijleven ◽  
Hans G X M Thomeer ◽  
Robert Stokroos ◽  
Inge Wegner
Keyword(s):  
Quality Of Life ◽  
Stapes Surgery ◽  
Institutional Review Board ◽  
Healthy Controls ◽  
Health Related Quality ◽  
Institutional Review ◽  
Related Quality ◽  
Health Related ◽  
Disease Specific

IntroductionOtosclerosis is a common cause of acquired conductive hearing loss and can be treated using hearing aids or surgically. Surgical success rates or surgical results are usually reported using pure-tone audiometric thresholds and/or speech discrimination scores. Audiometric results and patient-reported quality of life after stapes surgery do not seem to correlate well. It is therefore our opinion that health-related quality of life measurements should be implemented as an additional outcome measure after stapes surgery. So far, there is a lack of a valid, reliable and clinically feasible measuring tool for determining health-related quality of life in Dutch patients with otosclerosis who undergo stapes surgery.Methods and analysisA prospective validation study was designed to translate and validate the disease-specific Stapesplasty Outcome Test 25 (SPOT-25) in a population of Dutch patients with otosclerosis who undergo primary stapes surgery. A total of 125 patients with otosclerosis who will be undergoing primary stapes surgery and 50 healthy controls will be included. The patients with otosclerosis will fulfil several questionnaires preoperatively, 6 to 8 weeks postoperatively and 8 to 10 weeks postoperatively with a 2-week interval between the postoperative administrations. The patients’ audiometric results, which are measured routinely before and after undergoing primary stapes surgery, will also be used. The healthy controls will fulfil the translated SPOT-25 once. First, the original SPOT-25 will be translated from German to Dutch in a six-step process. Second, the translated SPOT-25 will be pilot-tested in a subset of patients. Lastly, validity, reliability and responsiveness of the translated SPOT-25 will be analysed.Ethics and disseminationThe research protocol was approved by the Institutional Review Board of the University Medical Center Utrecht (protocol 18–768/C; V.1, November 2018). Initially, we planned to include 50 patients. At a later stage we decided to increase the sample size to 100 patients. We notified the Institutional Review Board of this change to the protocol. The trial results will be disseminated through peer-reviewed medical journals and presented at scientific conferences.Trial registration numberNL7586.

Variability in Institutional Board Review for a Multisite Assessment of Resident Professionalism

2019 ◽  
Vol 14 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Judith A. Linden ◽  
Jeffrey I. Schneider ◽  
Andrea Cotter ◽  
Sabrina Drexel ◽  
Emily Frosch ◽  
...  
Keyword(s):  
Informed Consent ◽  
Educational Research ◽  
Research Study ◽  
Institutional Review Board ◽  
Professional Behaviors ◽  
National Board ◽  
Institutional Review ◽  
Board Review ◽  
Medical Examiners ◽  
Written Informed Consent

Residents serve as both trainees and employees and can be considered potentially vulnerable research participants. This can lead to variation in the institutional review board (IRB) review. We studied sites participating in the Assessment of Professional Behaviors Study sponsored by the National Board of Medical Examiners (2009-2011). Of the 19 sites, all but one were university affiliated. IRB review varied; 2/19 did not submit to a local IRB, 4/17 (23%) were exempt, 11/17 (65%) were expedited, and 2/17 (12%) required full Board review; 12/17 (71%) required written informed consent. The interval from submission to approval was 1 to 2 months (8/17); the range was 1 to 7 months. Although most stated there were no major barriers to approval, the most common concern was resident coercion and loss of confidentiality. Local IRB review of this educational research study varied.

Predictive Factors for Rapid Engraftment of Neutrophil and Platelet After Allogenic Peripheral Blood Stem Cell Transplantation in Patients with Hematologic Malignancies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4499-4499
Author(s):  
Ho Sup Lee ◽  
Lee Chun Park ◽  
Eun Mi Lee ◽  
Byeong Jin Ye ◽  
Joon Ho Moon ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Predictive Factors ◽  
Cd8 T Cells ◽  
P Value ◽  
Donor Age ◽  
Cd34 Cells ◽  
Cell Phenotypes

Abstract Abstract 4499 Background: CD34+ cell dose has been the most reliable measure for predicting the kinetics of hematopoietic reconstitution including rapid neutrophil and platelet engraftment in allogenic stem cell transplantation (AlloSCT). Moreover, cell phenotypes related with engraftment were reported that CD34+CD33- cells and CD34+CD41+ cells, CD26, and CD8+ cytotoxic T cells and CD56+ natural killer cells, were potential predictors of early engraftment in HCT. The purpose of our study is to investigate predictors which influence on early engraftment including cell phenotypes and clinical factors in patients with hematologic malignancy underwent AlloSCT in South Korea. Methods: Three hundred twenty four patients who received AlloSCT from at hematopoietic stem cell transplantation centers in South Korea between September 1998 and November 2011 were analyzed in this study. Subset analyses of the peripheral blood stem cells (PBSCs) and peripheral lymphocytes were conducted by using a flow-cytometric method. Two-color (FITC; PE) flow-cytometric immunophenotyping was performed. The hematopoietic stem cell (CD34+ cells), T cells (CD3+), helper T cells (CD3+/CD4+), cytotoxic T cells (CD3+/CD8+), and NK cells (CD56+) were all analyzed on a FACScan. And other clinical factors were analyzed in this study such as age, sex, disease status before AlloSCT, cormobidity index score, intensity of conditioning regimen, donor age, donor sex, and etc. The definitions of engraftment were more than 0.5×109/L and 20 ×109/L after AlloSCT in neutrophil and platelet, respectively. Results: In univariate analysis, predictive factors for engraftment of neutrophil at least day 12 were shown complete remission (CR) state befo re AlloSCT (p-value; 0.002), donor age less than 30 years old (0.004), mononuclear cell counts (MNC) more than 7.0 × 108/kg (p-value; 0.001), CD34+ cells more than 5.0 × 106/kg (p-value; 0.045), CD3+ T cells more than 3.0 × 108/kg (p-value; 0.002) and CD3+/CD8+ T cells more than 2.0 × 108/kg (p-value; 0.012). Predictive factors for engraftment of platelet at least day 14 were female (p-value; 0.004), shown complete remission (CR) state before AlloSCT (p-value; < 0.001), donor age less than 30 years old (0.006), mononuclear cell counts (MNC) more than 7.0 × 108/kg (p-value; < 0.001), CD34+ cells more than 5.0 × 106/kg (p-value; 0.050), CD3+ T cells more than 3.0 × 108/kg (p-value; < 0.001), CD3+/CD4+ T cells more than 3.0 × 108/kg (p-value; < 0.001), CD3+/CD8+ T cells more than 2.0 × 108/kg (p-value; < 0.001) and CD56+ NK cells (p-value; 0.001). In multivariate analysis, significant predictive factors for engraftment of neutrophil on day 12 was CR state before AlloSCT (RR; 0.466, 95% C.I.; 0.263 – 0.824, p-value; 0.009) and for engraftment of platelet on day 14 were female (RR; 2.230, 95% C.I.; 1.079 – 4.608, p-value; 0.030), CR state before AlloSCT (RR; 0.332, 95% C.I.; 0.165 – 0.669, p-value; 0.002), CD3+ T cells more than 3.0 × 108/kg (RR; 3.649, 95% C.I.; 1.659 – 8.030, p-value; 0.001), and CD3+/CD8+ T cells more than 2.0 × 108/kg (RR; 2.505, 95% C.I.; 1.123 – 5.587, p-value; 0.025). Conclusion: In our study, predictive factors for engrafment of neutrophil at least day 12 was CR state before AlloSCT and engraftment of platelet at least day 14 were female, CR state before AlloSCT, CD3+ T cells more than 3.0 × 108/kg and CD3+/CD8+ T cells more than 2.0 × 108/kg. However, further studies are needed to determine more impressive predictive cell phenotypes and clinical factors for engraftment of neutrophil and platelet after allogenic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Oral Fluid Cannabinoids in Chronic, Daily Cannabis Smokers during Sustained, Monitored Abstinence

2011 ◽  
Vol 57 (8) ◽  
pp. 1127-1136 ◽  
Author(s):  
Dayong Lee ◽  
Garry Milman ◽  
Allan J Barnes ◽  
Robert S Goodwin ◽  
Jussi Hirvonen ◽  
...  
Keyword(s):  
Oral Fluid ◽  
Research Unit ◽  
Driving Under The Influence ◽  
Institutional Review Board ◽  
Test Interpretation ◽  
Test Results ◽  
Detection Rates ◽  
Institutional Review ◽  
Detection Window ◽  
Written Informed Consent

BACKGROUND Oral fluid (OF) is an accepted alternative biological matrix for drug treatment, workplace, and DUID (driving under the influence of drugs) investigations, but establishing the cannabinoid OF detection window and concentration cutoff criteria are important. METHODS Cannabinoid concentrations were quantified in OF from chronic, daily cannabis smokers during monitored abstinence. Δ9-tetrahydrocannabinol (THC)3, cannabidiol (CBD), cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) were determined in daily OF samples collected with the Quantisal™ device. GC-MS limits of quantification (LOQ) were 0.5 μg/L for THC and CBD, 1 μg/L for CBN, and 7.5 ng/L for THCCOOH. RESULTS After providing written informed consent for this institutional review board–approved study, 28 participants resided from 4 to 33 days on the secure research unit and provided 577 OF specimens. At the LOQ, THC was generally quantifiable for 48 h, whereas CBD and CBN were detected only at admission. Median THCCOOH detection time was 13 days (CI 6.4–19.6 days). Mean THC detection rates decreased from 89.3% at admission to 17.9% after 48 h, whereas THCCOOH gradually decreased from 89.3% to 64.3% within 4 days. Criteria of THC ≥2 μg/L and THCCOOH ≥20 ng/L reduced detection to &lt;48 h in chronic cannabis smokers. An OF THCCOOH/THC ratio ≤4 ng/μg or presence of CBD or CBN may indicate more recent smoking. CONCLUSIONS THC, THCCOOH, CBD, and CBN quantification in confirmatory OF cannabinoid testing is recommended. Inclusion of multiple cannabinoid cutoffs accounted for residual cannabinoid excretion in OF from chronic, daily cannabis smokers and could reduce the potential for positive test results from passive cannabis smoke exposure and lead to greatly improved test interpretation.

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