scholarly journals Circulating Cell-Free Tumour DNA for Early Detection of Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3704
Author(s):  
Jedrzej J. Jaworski ◽  
Robert D. Morgan ◽  
Shivan Sivakumar
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Early Stage ◽  
Lower Sensitivity ◽  
Detection Rates ◽  
Early Stage Disease ◽  
Genetic Sequencing ◽  
Number Of Factors ◽  
Stage Disease ◽  
Invasive Method

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.

scholarly journals Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Cell Free Dna ◽  
Early Stage Disease ◽  
Non Invasive ◽  
Cancer Pathogenesis ◽  
Free Dna ◽  
Stage Disease ◽  
Circulating Cell Free Dna

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 349-349
Author(s):  
Heather Stuart ◽  
Caroline Ripat ◽  
Basem Azab ◽  
Danny Yakoub ◽  
Dido Franceschi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Clinical Stage ◽  
Stage I ◽  
Clinical Staging ◽  
Early Stage Disease ◽  
Risk Of Mortality ◽  
Stage Disease ◽  
Pathologic Staging ◽  
Group 2

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p < 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p < 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p < 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

scholarly journals ctDNA in Breast Milk for Early Detection of Pregnancy Associated Breast Cancer

2021 ◽  
Author(s):  
Miriam Sanso ◽  
Cristina Saura ◽  
Carolina Ortiz ◽  
Enrique Arenas Lahuerta ◽  
Judit Matito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Milk ◽  
Early Detection ◽  
Early Stage ◽  
Early Stage Disease ◽  
Genetic Profiling ◽  
Non Invasive ◽  
Milk Serum ◽  
Stage Disease ◽  
Localized Disease

Abstract Pregnancy associated breast cancer (PABC) is an overall poor prognosis group compared to non-PABC breast cancer (BC), mainly due to late diagnosis. Effective screening approaches for early detection may improve its outcome. For the first time, we demonstrate the presence of cell-free tumor DNA (ctDNA) in the breast milk serum (sBM) of PABC in patients with early-stage disease and its ability to recapitulate somatic mutations present in the primary tumor. Moreover, our results demonstrate that sBM robustly surpasses plasma for tumor genetic profiling due to a prevalent shedding of ctDNA into the sBM in localized disease, as well as increased total cell-free DNA (cfDNA) abundance and integrity. Thus, we propose sBM as a potential new non-invasive liquid biopsy for a prompt detection of PABC.

scholarly journals Impact of an Early Detection Program on Breast Cancer Services, Incidence, and Stage in Rural Rwanda

2018 ◽  
Vol 4 (Supplement 3) ◽  
pp. 34s-34s ◽  
Author(s):  
Lydia E. Pace ◽  
Nancy L. Keating ◽  
Jean-Marie Vianney Dusengimana ◽  
Vedaste Hategekimana ◽  
Vestine Rugema ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Low Income ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Early Stage Disease ◽  
Entire Study ◽  
Detection Program ◽  
Stage Disease ◽  
Early Detection Program

Purpose In low-income countries, most women with breast cancer present with advanced-stage disease. To facilitate earlier diagnoses of symptomatic disease, feasible and effective early detection strategies are needed. We assessed health care use and patient outcomes from a randomized pilot study of an early detection program in Burera, a rural Rwandan district, where the Butaro Cancer Center of Excellence (BCCOE) is located. Methods The intervention included training for community health workers in breast health, training for health center (HC) nurses in the evaluation of breast concerns, and weekly breast clinics at HCs and BCCOE. Twelve of 18 eligible HCs were randomly assigned to receive the intervention—seven beginning in April and May 2015, and five in November and December 2015—and six served as controls for the entire study period. We abstracted HC and hospital records of patients seen between April 2015 and April 2017 and used generalized linear models to compare the incidence of biopsies, breast cancer diagnoses, and early-stage diagnoses in the geographic sectors served by intervention versus control HCs. Results Overall, 276,282 person-years were in intervention sectors and 302,856 in control sectors. Of patients, 1,500 patients sought care at intervention HCs for breast concerns versus 600 at control HCs. Three hundred eighteen patients that were referred from intervention HCs were evaluated at BCCOE compared with 62 from control HCs. The biopsy rate was 36.6 per 100,000 person-years from intervention sectors versus 8.9 per 100,000 from control sectors ( P < .001). Breast cancer was diagnosed in 19 of 101 patients from intervention HCs who underwent biopsy (18.8%) compared with 10 (37.0%) of 27 patients from control HCs. Breast cancer incidence was 6.9 per 100,000 in intervention sectors versus 3.3 per 100,000 in control sectors ( P = .35). Nine patients from intervention HCs had early-stage disease (47.4%) versus two from control HCs (20.0%). The incidence rate of early-stage breast cancer was 3.7 per 100,000 in intervention sectors versus 0.7 per 100,000 in control sectors ( P = .08). Conclusion Over 2 years, our early detection program was associated with more patients referred for hospital-level evaluation and requiring biopsies. Most patients referred by intervention HCs had benign conditions; however, there was a trend toward a higher incidence of early-stage breast cancer among patients from intervention regions. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Lydia E. Pace Stock or Other Ownership: Firefly Health

Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

2012 ◽  
Vol 109 ◽  
pp. 1-7 ◽  
Author(s):  
Michael Marberger ◽  
Jelle Barentsz ◽  
Mark Emberton ◽  
Jonas Hugosson ◽  
Stacy Loeb ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
Early Stage Disease ◽  
Prostate Cancer Diagnosis ◽  
Diagnosis And Management ◽  
Stage Disease ◽  
Novel Approaches ◽  
Improve Prostate Cancer

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Female Breast Cancer in Suriname: Pathways to Treatment—A Patient’s Perception

2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 49-49
Author(s):  
Euridice R. Irving ◽  
Dennis R. A. Mans ◽  
Els Th. M. Dams ◽  
Maureen Y. Lichtveld
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Access To Health Care ◽  
Early Stage ◽  
Diagnosis And Treatment ◽  
Related Factors ◽  
Entire Interval ◽  
Early Stage Disease ◽  
Resource Setting ◽  
Stage Disease

PURPOSE Delays across the entire cancer care continuum are not uncommon. This cross-sectional study explored the health care trajectories of Surinamese women with breast cancer and identified predictors of timely diagnosis and treatment initiation. METHODS One hundred women age 30 years or older who were newly diagnosed with breast cancer in 2017 to 2018 were recruited from all 4 hospitals in Paramaribo. Data on their demographics, lifestyle, reproductive and medical history, health status, and family history of breast cancer and other malignancies were collected using a validated semistructured questionnaire. Using Anderson’s Model of Pathways to Treatment, we defined a patient interval (from detection to first consultation), diagnostic interval (from consultation to histopathologic diagnosis), and treatment interval (from diagnosis to first treatment). Log-transformed data were analyzed using linear regression, and variables with P ≤ .05 were considered statistically significant predictors of intervals. RESULTS All participants had health insurance and access to health care. Eighty-five percent of patients presented with early-stage disease. Ninety percent of patients had self-detected their disease, with 70% finding a lump. Average age was 55.6 years (± 11.8 years). Median durations of patient, diagnostic, and treatment intervals were 13 days (interquartile, range, 4-63 days), 40 days (IQR, 21-57 days), and 18 days (IQR, 8-38 days), respectively. Median duration of the entire interval was 95 days (IQR, 59-272 days). Patient-related factors associated with the intervals were religion (β = −530; P = .003), being employed (β = 149.4; P = .007), and age 50 years and older (β = −195.8; P = .037). Disease-related factors were lump as first symptom (β = −175.6; P = .038) and late-stage disease at diagnosis (β = 213.5; P = .004). CONCLUSION Given the limited-resource setting, delays in Suriname’s health care can be minimized by programs aimed at increasing breast cancer awareness and education; however, delays may have been underestimated as a result of the over-representation of early-stage disease and recall bias regarding the first symptom detected.

scholarly journals Detection of KRAS Mutations in Circulating Tumor DNA by Digital PCR in Early Stages of Pancreatic Cancer

2016 ◽  
Vol 62 (11) ◽  
pp. 1482-1491 ◽  
Author(s):  
Nora Brychta ◽  
Thomas Krahn ◽  
Oliver von Ahsen
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Surgical Removal ◽  
Plasma Samples ◽  
Kras Mutations ◽  
Detection Rates ◽  
Early Stages ◽  
Tumor Dna

Abstract BACKGROUND Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool for pancreatic cancer, which typically causes clinical symptoms only in advanced stage. Because of their high prevalence in pancreatic cancer, KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested the diagnostic sensitivity of chip based digital PCR for the detection of KRAS mutations in circulating tumor DNA (ctDNA) in early stage pancreatic cancer. METHODS We analyzed matched plasma (2 mL) and tumor samples from 50 patients with pancreatic cancer. Early stages (I and II) were predominant (41/50) in this cohort. DNA was extracted from tumor and plasma samples and tested for the common codon 12 mutations G12D, G12V, and G12C by chip-based digital PCR. RESULTS We identified KRAS mutations in 72% of the tumors. 44% of the tumors were positive for G12D, 20% for G12V, and 10% for G12C. One tumor was positive for G12D and G12V. Analysis of the mutations in matched plasma samples revealed detection rates of 36% for G12D, 50% for G12V, and 0% for G12C. The detection appeared to be correlated with total number of tumor cells in the primary tumor. No KRAS mutations were detected in 20 samples of healthy control plasma. CONCLUSIONS Our results support further evaluation of tumor specific mutations as early diagnostic biomarkers using plasma samples as liquid biopsy.

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