Analytical validation of a tumor-agnostic integrated multianalyte circulating tumor DNA (ctDNA) assay in early-stage cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3057-3057
Author(s):  
Anna Hartwig ◽  
Carlo Artieri ◽  
Ariel Jaimovich ◽  
Emily E. Van Seventer ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Late Stage ◽  
Tumor Tissue ◽  
Limit Of Detection ◽  
Early Stage ◽  
White Blood Cells ◽  
Circulating Tumor Dna ◽  
P Value ◽  
Analytical Sensitivity ◽  
Early Stage Disease ◽  
Tumor Level

3057 Background: ctDNA sequencing has been rapidly adopted for the identification of targetable somatic alterations (alts) in patients with advanced cancers. However, early stage disease detection has been hindered by low levels of ctDNA in circulation and the presence of confounding non-tumor-related somatic alts. We developed and validated a ctDNA assay that combines somatic and epigenomic signals to detect early stage tumors without tumor tissue or white blood cells (WBC). Methods: Using a single input sample, our assay integrates the sensitive detection of genomic alts with quantification of epigenomic signals associated with cancer. Non-tumor alts (e.g., clonal hematopoiesis of indeterminate potential; CHIP) are excluded using a newly developed bioinformatic classifier. To assess analytical sensitivity, specificity, and positive and negative reproducibility, we tested 337 clinical and contrived samples. Results: Clinical specificity was determined using 80 plasma samples from 50-75 year old presumptive cancer-free donors, and resulted in a single false positive (99% specificity). Analytical sensitivity (limit of detection) was established using a dilution series of 4 different late stage CRC pts tested in triplicate at a clinically relevant DNA input (30 ng) across multiple batches. 100% sensitivity was maintained even at the lowest tested level (estimated 0.1% tumor level). Positive/negative reproducibility was assessed by testing triplicates of diluted late stage samples and age-matched healthy donors, respectively, across different cfDNA inputs, and multiple reagent lots. Both positive and negative calls were 100% concordant across all replicates. Independent estimation of tumor levels from epigenomic or genomic signals produced highly concordant results (correlation r-value: 0.82, p-value: 3e-16). Conclusions: We designed and validated a highly specific ctDNA assay that integrates both genomic and epigenomic signals to allow for accurate and quantitative tumor level detection in early stages of the disease without requiring tumor tissue or WBC.

Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8517-8517
Author(s):  
Davina Gale ◽  
Katrin Heider ◽  
Malcolm Perry ◽  
Giovanni Marsico ◽  
Andrea Ruiz-Valdepeñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Sequencing ◽  
Early Stage ◽  
Post Treatment ◽  
Disease Stage ◽  
Analytical Sensitivity ◽  
Disease Relapse ◽  
Clinical Progression ◽  
Liquid Biopsies ◽  
Early Stage Disease

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.

scholarly journals Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 596 ◽  
Author(s):  
Jing Guo ◽  
Wei-Lei Yang ◽  
Daewoo Pak ◽  
Joseph Celestino ◽  
Karen H. Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Late Stage ◽  
Early Stage ◽  
Characteristic Curve ◽  
Stage I ◽  
Inhibitory Factor ◽  
Early Stage Disease ◽  
Biomarker Panel ◽  
Early Stage Ovarian Cancer

Early detection of ovarian cancer promises to reduce mortality. While serum CA125 can detect more than 60% of patients with early stage (I–II) disease, greater sensitivity might be observed with a panel of biomarkers. Ten protein antigens and 12 autoantibody biomarkers were measured in sera from 76 patients with early stage (I–II), 44 patients with late stage (III–IV) ovarian cancer and 200 healthy participants in the normal risk ovarian cancer screening study. A four-biomarker panel (CA125, osteopontin (OPN), macrophage inhibitory factor (MIF), and anti-IL-8 autoantibodies) detected 82% of early stage cancers compared to 65% with CA125 alone. In early stage subjects the area under the receiver operating characteristic curve (AUC) for the panel (0.985) was significantly greater (p < 0.001) than the AUC for CA125 alone (0.885). Assaying an independent validation set of sera from 71 early stage ovarian cancer patients, 45 late stage patients and 131 healthy women, AUC in early stage disease was improved from 0.947 with CA125 alone to 0.974 with the four-biomarker panel (p = 0.015). Consequently, OPN, MIF and IL-8 autoantibodies can be used in combination with CA125 to distinguish ovarian cancer patients from healthy controls with high sensitivity. Osteopontin appears to be a robust biomarker that deserves further evaluation in combination with CA125.

Vaginal sarcoma: the Royal Marsden experience

1994 ◽  
Vol 4 (5) ◽  
pp. 337-341 ◽  
Author(s):  
H. Y.S. Ngan ◽  
J. H. Shepherd ◽  
C. Fisher ◽  
P. Blake
Keyword(s):  
Late Stage ◽  
Poor Prognosis ◽  
Recurrent Disease ◽  
Early Stage ◽  
Tumor Grade ◽  
Intermediate Grade ◽  
Early Stage Disease ◽  
The Poor ◽  
Stage Disease ◽  
Prognostic Importance

Six patients with vaginal sarcoma are reported here. This clinicopathologic review confirms the poor prognosis of this disease. However, there were three 5-year survivors, all of whom had early stage disease and low to intermediate grade tumors. Apart from tumor grade, stage was of prognostic importance. Late recurrences at 5 and 21 years were noted in two of the three 5-year survivors. Neither chemotherapy nor radiotherapy were of use in the treatment of late stage or recurrent disease.

Frequency of late-stage breast cancer diagnoses despite high mammography screening rates in an HMO

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1526-1526
Author(s):  
R. Haque ◽  
J. E. Schottinger ◽  
M. H. Kanter ◽  
C. C. Avila ◽  
R. Contreras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Late Stage ◽  
Mammography Screening ◽  
Early Stage ◽  
Advanced Tumor Stage ◽  
Early Stage Disease ◽  
Advanced Tumor ◽  
Stage Disease ◽  
Late Stage Diagnosis ◽  
The Impact

1526 Background: Kaiser Permanente Southern California (KPSC) led the nation in screening women for breast cancer (BCa) with a mammography rate of nearly 90% in 2007 according to 2008 Healthcare Effectiveness Data and Information Set (HEDIS) measures. Despite successes in improving screening rates in this health plan that serves 3+ million diverse members, the percentage of women diagnosed with late stage BCa (stage III, IV) remained stable, varying from 12.9% (N∼323) in 2003 to 10.8% (N∼270) in 2007. To identify patient and health care factors associated with late stage diagnosis and the impact of its enhanced screening implementation guidelines, KPSC undertook this study. Methods: This cross-sectional study included a cohort of 10,580 BCa patients from 2003–2007. We compared women diagnosed with late stage disease versus those with early stage disease (stages I, II). P values (2-sided) were based on the chi-square distribution. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. Results: Factors that were positively associated with late stage diagnosis in the univariate analyses included age, lack of recent mammography screening, worse tumor features, 80+ years of age, minority race, lower geocoded household income, increased healthcare visits, and use of Pap testing (P < 0.01 for all variables). Factors significantly associated with late stage diagnosis in the multivariate model included only lack of recent mammography screening (OR = 1.35, 95% CI: 1.14–1.58) and worse tumor features including high grade (grade 3, OR = 2.58, 95% CI: 1.96–3.40), positive lymph nodes (OR = 53.49, 95% CI: 39.90–71.72), and HER-2+ tumors (OR = 1.40, 95% CI: 1.13–1.72). Conclusions: Targeting older women, those with lower utilization, and women who did not have a recent mammogram may help further lower the prevalence of late stage diagnoses. However, given the extent of the health plan's previous efforts to enhance BCa screening rates, a ceiling effect may limit additional benefit. Additional efforts to decrease the rate of advanced tumor stage at diagnosis may include improving interpretation of mammograms or earlier detection of aggressive tumors by enhanced BRCA genetic testing. No significant financial relationships to disclose.

Association of serum levels of the growth factor GP88 with disease progression in breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22021-e22021
Author(s):  
G. Serrero ◽  
K. Tkaczuk ◽  
M. Zhan ◽  
N. Tait ◽  
C. Ilan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Serum Level ◽  
Disease Progression ◽  
Cancer Patients ◽  
Early Stage ◽  
Serum Levels ◽  
P Value ◽  
Breast Cancer Patients ◽  
Early Stage Disease

e22021 Background: The autocrine growth factor GP88 is an important player in breast cancer. GP88 is expressed in human BC tumors in correlation with their tumorigenicity. Increased GP88 expression was associated with anti-estrogen therapy resistance in ER+ cells and Herceptin resistance in Her-2 overexpressing breast tumors. Inhibition of GP88 expression inhibited tumor incidence and growth in nude mice. Immunohistochemical studies have shown that GP88 is expressed in invasive ductal carcinomas (IDC) and that high GP88 expression correlated with increased recurrence and mortality. Since GP88 is found in serum, we hypothesized that GP88 was elevated in the sera of breast cancer patients compared to healthy individuals and that GP88 serum level increases with disease progression. Methods: An IRB approved prospective study was established at the University of Maryland Breast Clinic to determine the serum level of GP88 in breast cancer patients (BC pts). Approximately 5 ml of blood was drawn every three months. GP88 serum concentration was determined in triplicate by human GP88 enzyme immunoassay. 190 BC pts were accrued. Sera from healthy volunteers (HV) were obtained to establish GP88 baseline. BC patient characteristics: Caucasian- 91, African American-92, Asian-6; median age, 51 (range 29- 86), stage I - 48, II - 52, III - 26, IV - 63. Results: Median serum GP88 level was 28.7 ng/ml (range 16.6–38.2) in HV, 40.7 ng/ml (range 6.4–100) in early stage (stage 1 -3) BC pts (p- value = 0.007) and 45.3 ng/ml (range 9.8 to 158.4) in stage 4 BC patients (p- value= 0.0007). Statistically significant increase in serum GP88 level was found in early stages as well as in metastatic disease when compared to HV. In addition, patients that were initially diagnosed with early stage disease but recurred showed a 5 to 10 fold increase in their GP88 serum levels. Conclusions: GP88 serum level is significantly higher in the sera of BC than HV subjects. Moreover, GP88 serum level increased in association with disease recurrence and progression. This study identifies GP88 as a measurable biomarker for disease progression not only at the tissue but also at the serum level. These results are also interesting since GP88 is also a therapeutic target of malignant progression of breast carcinoma. No significant financial relationships to disclose.

Non-invasive diagnosis and tracking of tumor evolution by targeted sequencing of circulating tumor DNA in metastatic pancreatic cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15769-e15769
Author(s):  
Thomas Seufferlein ◽  
Andreas W. Berger ◽  
Daniel Schwerdel ◽  
Thomas Jens Ettrich ◽  
Stefan A. Schmidt ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Early Stage ◽  
Therapy Monitoring ◽  
Circulating Tumor Dna ◽  
Ductal Adenocarcinoma ◽  
Tumor Evolution ◽  
Imaging Data ◽  
Non Invasive ◽  
Outcome Monitoring ◽  
Tumor Dna

e15769 Background: Treatment of stage IV pancreatic ductal adenocarcinoma (PDAC) has made substantial progress over the last years, therapy monitoring still is at an early stage. This could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor even during treatment. In particular, non-invasive approaches are desirable. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Methods: We analyzed a cohort of 20 patients with histologically confirmed metastatic PDAC (mPDAC) prior to and during palliative treatment including disease progression. ctDNA and corresponding tumor tissue were analyzed by targeted NGS and droplet digital PCR for the 7 most frequently mutated genes in PDAC ( TP53, SMAD4, CDKN2A, KRAS, APC, ATM, FBXW7). Findings were correlated with clinical and imaging data to establish its prognostic and predictive value. Results: ctDNA was analyzed at baseline prior to initiation of the respective line of treatment. Mutations in either of the genes examined were detectable in 15/20 patients (75%). Tissue-blood concordance was 80% in therapy naïve patients. 96% of mutations in ctDNA of therapy naïve patients were in KRAS and/or TP53. The combined mutated allele frequencies (CMAF) of theese 2 genes significantly decreased (p = 0.0173) during therapy and increased at progression (p = 0.0145) across all treatment lines. By sequential ctDNA analyses we detected a change in the mutational landscape compared to the respective baseline ctDNA status in 7/11 patients during 1st line, in 3/7 patients during 2nd line and 2/2 patients during 3rdline treatment. In therapy naïve patients, the decline of the CMAF during therapy significantly correlated with progression-free survival (p = 0.0013). Conclusions: Molecular genotyping of ctDNA in mPDAC patients proved to be feasible and there was a high concordance between tumor tissue and ctDNA. The molecular genotype changed significantly during treatment and changes correlated with outcome. Monitoring of ctDNA may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3056-3056
Author(s):  
B.E. Shaw ◽  
N.P. Mayor ◽  
A.-M. Little ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
...  
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
Disease Stage ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Early Stage Disease ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Multiple Loci ◽  
Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

scholarly journals Molecular estimation of neurodegeneration pseudotime in older brains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumit Mukherjee ◽  
Laura Heath ◽  
Christoph Preuss ◽  
Suman Jayadev ◽  
Gwenn A. Garden ◽  
...  
Keyword(s):  
Late Stage ◽  
Late Onset ◽  
Early Stage ◽  
Disease Onset ◽  
Postmortem Brain ◽  
Disease Stage ◽  
Rna Seq ◽  
Early Stage Disease ◽  
Molecular Changes ◽  
Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

Prevalence of inferred clonal hematopoiesis (CH) detected on comprehensive genomic profiling (CGP) of solid tumor tissue or circulating tumor DNA (ctDNA).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3009-3009
Author(s):  
Emmanuel S. Antonarakis ◽  
Zheng Kuang ◽  
Hanna Tukachinsky ◽  
Christine Parachoniak ◽  
Andrew David Kelly ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Tissue ◽  
White Blood Cells ◽  
Pathogenic Mutation ◽  
Circulating Tumor Dna ◽  
Continuous Variable ◽  
Allelic Frequency ◽  
Comprehensive Genomic Profiling ◽  
Clinically Significant ◽  
Solid Tumor Tissue

3009 Background: The increased use of ctDNA CGP has paralleled increased detection and interest in CH, which can confound CGP results from ctDNA or tissue, and can be associated with hematologic and cardiovascular morbidity. However, paired-depth sequencing of white blood cells (WBC) for confirmation of CH is not widely available. We here study the prevalence of inferred CH (iCH), which refers to incidental detection on routine clinical CGP of variants attributable to CH due to their known CH association and their negligible prevalence in solid tumors. Methods: A database of clinical CGP results was reviewed, including two 324-gene NGS panels for tumor tissue (FoundationOne CDx) and plasma ctDNA (FoundationOne Liquid CDx). Analysis was limited to NSCLC, breast, prostate, colorectal, and pancreatic cancers. iCH was defined as any pathogenic mutation in ASXL1, DNMT3A, and TET2, and prespecified mutations in JAK2, SF3B1, U2AF1, MYD88, IDH2, MPL, CBL. Variant allelic frequency (VAF) > 2% was considered clinically significant and VAF > 10% was considered high risk. Results: 100,905 total cases were studied; median age was 65 for tissue CGP and 68 for ctDNA. iCH was more commonly detected in ctDNA (1468/2891, 51%) than in tissue (9416/97993, 10%). Among cases with any iCH detected, multiple iCH mutations were seen more commonly in ctDNA (640/2891, 22%) than in tissue (987/98014, 1%). Focusing on clinically significant iCH ( > 2% VAF), prevalence remained higher in ctDNA (22%, 637) than in tissue (8%, 7878), while the higher sensitivity of ctDNA testing identified more low level iCH (< 2% VAF, 40% in ctDNA, 2% in tissue). Across cancer types, iCH > 2% was consistently more common in ctDNA (Table). As expected, prevalence of iCH > 2% increased with age (continuous variable, p < 0.001). High risk iCH ( > 10% VAF) was seen in 4% of total cases (most commonly ASXL1, TET2, DNMT3A); 1% of all cases had multiple clinically significant iCH variants ( > 2% VAF). Focusing on a subset of 439 cases with both tissue and ctDNA results (median 1.5 months between samples), 290 iCH mutations were detected in ctDNA (median VAF 1%) but only 38 in tissue (median VAF 9%). Conclusions: Inferred CH is common on somatic CGP of cancer patients, with a high prevalence in ctDNA likely due to the deeper sequencing depth and WBC contamination. For the minority of patients with high VAF iCH, further research is needed to understand whether this might be representative of an occult hematologic condition deserving of further evaluation.[Table: see text]

The Effect of Increasing Two-Week Wait Referrals for Head and Neck Cancer in East Kent

2011 ◽  
Vol 93 (6) ◽  
pp. 217-220 ◽  
Author(s):  
S Haikel ◽  
N Dawe ◽  
G Lekakis ◽  
M Black ◽  
D Mitchell
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Late Stage ◽  
Early Stage ◽  
White Paper ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Late Stage Disease ◽  
The Uk

In 1998 the UK government published its white paper The New NHS: Modern and Dependable, in which it first suggested that patients being referred with a suspicion of cancer should have a maximum wait of two weeks to see a specialist. The rationale for this was that outcomes for late-stage disease are significantly worse when compared with outcomes for early-stage disease (Table 1). It was assumed that reducing the wait to see a specialist would reduce the stage of disease at presentation.

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