scholarly journals Liquid biopsy in peritoneal fluid and plasma as a prognostic factor in advanced colorectal and appendiceal tumors after complete cytoreduction and hyperthermic intraperitoneal chemotherapy

2020 ◽  
Vol 12 ◽  
pp. 175883592098135
Author(s):  
Irene López-Rojo ◽  
Susana Olmedillas-López ◽  
Pedro Villarejo Campos ◽  
Víctor Domínguez Prieto ◽  
Javier Barambio Buendía ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Intraperitoneal Chemotherapy ◽  
Liquid Biopsy ◽  
Peritoneal Fluid ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Before And After ◽  
Colorectal Origin ◽  
Systemic Relapse

Background: Positive cytology has been identified as an independent negative prognostic factor in patients with peritoneal metastases (PM) of colorectal origin. Liquid biopsy in plasma may detect increasing levels of circulating tumor DNA (ctDNA) and could help predict systemic relapse in patients with colorectal cancer, but little is known about the role of liquid biopsy in peritoneal fluid. The aim of this study was to evaluate the prognostic value of peritoneal fluid and plasma liquid biopsy in patients undergoing complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CC-HIPEC). Methods: A longitudinal prospective study was designed in patients with KRAS-mutated colorectal or appendiceal primary tumor, including PM of colorectal origin, pseudomyxoma peritonei and patients at high risk of developing PM (selected for second-look surgery). Eleven patients were recruited according to inclusion and exclusion criteria. ctDNA from plasma and peritoneal fluid before and after HIPEC was studied by droplet digital PCR looking for KRAS mutation. A close follow-up was scheduled (mean of 28.5 months) to monitor for systemic and peritoneal recurrences. Results: All patients with positive plasma postHIPEC had systemic relapse and four patients died as a result, while those with negative plasma postHIPEC did not relapse. Patients with negative peritoneal ctDNA after CC-HIPEC did not present peritoneal relapse. Of six patients with positive peritoneal ctDNA postHIPEC, two presented peritoneal recurrence and four systemic relapses. Conclusions: Treatment with CC-HIPEC does not always neutralize ctDNA in peritoneal fluid, and its persistence after treatment may predict adverse outcome. Despite being a proof of concept, an adequate correlation between liquid biopsy in plasma and peritoneal fluid with both systemic and peritoneal relapse has been observed.

scholarly journals Multiple Hotspot Mutations Scanning by Single Droplet Digital PCR

2018 ◽  
Vol 64 (2) ◽  
pp. 317-328 ◽  
Author(s):  
Charles Decraene ◽  
Amanda B Silveira ◽  
François-Clément Bidard ◽  
Audrey Vallée ◽  
Marc Michel ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Limit Of Detection ◽  
Clinical Importance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Droplet Digital Pcr ◽  
Egfr Mutations ◽  
Detection Accuracy ◽  
Exon 2 ◽  
Exon 19

Abstract BACKGROUND Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. METHODS We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. RESULTS The KRAS and EGFR assays were highly specific and both reached a limit of detection of <0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. CONCLUSIONS This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy.

Circulating tumor DNA as a prognostic factor in peritoneal carcinomatosis after hyperthermic intraperitoneal chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16280-e16280
Author(s):  
Zongyuan Li ◽  
Xiaolin Pu ◽  
Hua Jiang
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Tumor Markers ◽  
Intraperitoneal Chemotherapy ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Peritoneal Cancer Index ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Peritoneal Cancer ◽  
Time Points ◽  
Tumor Dna

e16280 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is the main treatment for peritoneal carcinomatosis (PC).However, It is still a major problem to predict the efficacy of HIPEC. Some studies have shown that peritoneal cancer index (PCI) can be used to predict the efficacy of HIPEC, but the invasiveness and inaccuracy are shortcomings. Therefore, we need a minimally invasive and accurate prediction biomarker. Many studies have confirmed that circulating tumor DNA (ctDNA) can accurately predict the efficacy and prognosis of various solid tumors. This study aimed to evaluate the predictive value of ctDNA from ascites and plasma for HIPEC. Methods: Eligible PC patients should be defintive diagnosed by pathology or cytology. Each patient was treated with HIPEC for 4 times, with an interval of 3 days each time. Plasma and ascites samples were collected before HIPEC and after the last HIPEC. All samples were detected by next generation sequencing (NGS). The molecular tumor burden index (mTBI) and main clone variant allele fraction (VAF) changes were used as the prediction indexes of efficacy. In addition, The changes of common tumor markers such as CEA during the same period were used as controls. Results: A total of 19 patients with PC were enrolled from November 2018 to January 2020. Firstly, the mTBI changes of 14 patients whom had plasma samples at two time points (baseline and postHIPEC)were analyzed. Among them, 3 patients had no gene mutation were detected in two time points. There were significant differences in mTBI before and after HIPEC in the remaining 11 patients (Wilcoxon， p = 0.026). the median Ascites progression free survival (PFS) was 3.35 months (95% CI: 2.34 – 5.13 months), and the median overall survival (OS) was 5.93 months (95% CI: 4.93 – 11.17 months). The mTBI decline was significantly positively correlated with ascites PFS (Spearman r = 0.673, p = 0.023) and moderately positively correlated with OS (Spearman r = 0.510, p = 0.109). The highest VAF in plasma samples was defined as the main clone mutation. The main clone VAF decline was moderately positively correlated with ascites PFS (Spearman r = 0.588, p = 0.057) and slightly positively correlated with OS (Spearman r = 0.386, p = 0.241). As the controls, We found that the common tumor markers decline was no correlated with ascites PFS(Spearman r = 0.091, p = 0.790) and OS (Spearman r = 0.287, p = 0.396). We further analyzed the correlation of VAF between ascites and plasma co-mutation genes in 12 patients. The VAF of co-mutated genes in plasma and ascites was positively correlated (Spearman r = 0.794, p = 0.001). Conclusions: Plasma ctDNA can be used as a biomarker for predicting the efficacy of HIPEC for peritoneal carcinomatosis, and its accuracy is significantly higher than comon tumor markers. However, a larger sample size study are needed to validate our results.

Peritoneal metastases of colorectal origin – cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect

2017 ◽  
Vol 89 (6) ◽  
pp. 1-6
Author(s):  
Tomasz Jastrzębski ◽  
Marek Bębenek
Keyword(s):  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Distant Metastases ◽  
Peritoneal Metastases ◽  
Medical Procedures ◽  
Financial Loss ◽  
Colorectal Origin ◽  
Crs And Hipec ◽  
Financial Aspect

About 10% to 15% of patients with colon cancer have intraperitoneal metastases at diagnosis. The patients with intraperitoneal metastases and without distant metastases can benefit from cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Because up to a half of patients live for at least 5 years after this treatment, the treatment is used more and more often. The treatment of patients with intraperitoneal metastases with CRS and HIPEC costs more than the majority of other medical procedures, because CRS is extensive and takes a lot of time, and after surgery, patients need intensive care and expensive medications and equipment. Currently, only 40% to 80% of costs of CRS and HIPEC are reimbursed in Poland. Because CRS and HIPEC mean a financial loss to hospitals, they are rarely performed. We analyzed the costs of treating patients with peritoneal metastases by CRS and HIPEC in two centers (Gdank, Wroclaw) and showed how this treatment is reimbursed outside Poland. We discussed whether adequate qualification of patients and experience of the teams giving the treatment could reduce the costs.

Liquid biopsy leads to a paradigm shift in cancer treatment.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 602-602
Author(s):  
Koichi Suzuki ◽  
Yuji Takayama ◽  
Kosuke Ichida ◽  
Taro Fukui ◽  
Nao Kakizawa ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Multiple Testing ◽  
Poor Response ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Initial Assessment ◽  
Tumor Tissues ◽  
Time Changes ◽  
Colorectal Cancer Patients ◽  
Monitoring Treatment

602 Background: Liquid biopsy represents an ideal non-invasive tool allowing multiple testing over time, monitoring real time changes occurring within the tumor and evaluation of therapeutic response. Here we show monitoring of KRAS mutation in detection of circulating tumor DNA (ctDNA) during treatments for metastatic colorectal cancer patients (pts). Methods: 238 plasma samples were collected from 57 pts who underwent chemotherapy. KRAS mutant ctDNA (MctDNA) was determined by digital PCR as a tool of Liquid biopsy, detecting rare mutant clones in blood. Results: KRAS assessment in tumor tissues showed 19 pts with mutation (M) and 38 without mutation (W). Among 19 pts with M, 12 pts displayed MctDNA at the initial assessment and 7 pts showed no MctDNA. Then, one (M*) of 7 pts exhibited MctDNA during treatments. While 38 pts with W showed no MctDNA before chemotherapy except one pt (M**), 4 pts exhibited MctDNA after treatments with different regimens. MctDNA was detectable in the blood of these 4 pts prior to radiographic detection of disease progression. Regardless of KRAS status in tumor tissues, poor response was seen in pts with MctDNA. Conclusions: Liquid biopsy provides us a circulating biomarker for monitoring treatment response and choice of optimal regimens. [Table: see text]

scholarly journals Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

2020 ◽  
Vol 230 (4) ◽  
pp. 679-687
Author(s):  
Katharine E. Duckworth ◽  
Richard P. McQuellon ◽  
Gregory B. Russell ◽  
Kathleen C. Perry ◽  
Chandylen Nightingale ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Before And After ◽  
Caregiver Quality

scholarly journals Quantitative Analysis and Monitoring of EZH2 Mutations Using Liquid Biopsy in Follicular Lymphoma

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 785
Author(s):  
Ákos Nagy ◽  
Bence Bátai ◽  
Alexandra Balogh ◽  
Sarolta Illés ◽  
Gábor Mikala ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mutation Analysis ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Allele Frequencies ◽  
Variant Allele ◽  
Monitoring Tool ◽  
Positron Emission ◽  
Tumor Dna

Recent advances in molecular technologies enable sensitive and quantitative assessment of circulating tumor DNA, offering a noninvasive disease monitoring tool for patients with malignant disorders. Here, we demonstrated on four follicular lymphoma cases that circulating tumor DNA based EZH2 mutation analysis performed by a highly sensitive droplet digital PCR method may be a valuable treatment monitoring approach in EZH2 mutant follicular lymphoma. EZH2 variant allele frequencies changed in parallel with the volume of metabolically active tumor sites observed on 18F-fluorodeoxyglucose positron emission tomography combined with computer tomography (PET-CT) scans. Variant allele frequencies of EZH2 mutations decreased or were eliminated rapidly upon successful treatment, with treatment failure being associated with elevated EZH2 variant allele frequencies. We also demonstrated spatial heterogeneity in a patient with two different EZH2 mutations in distinct anatomical sites, with both mutations simultaneously detected in the liquid biopsy specimen. In summary, circulating tumor DNA based EZH2 mutation analysis offers a rapid, real-time, radiation-free monitoring tool for sensitive detection of EZH2 mutations deriving from different anatomical sites in follicular lymphoma patients receiving immunochemotherapy.

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