Hepatic Carcinoma Malignant Primary Non-Resectable
Conditions
Keywords
Hepatocellular carcinoma, Cell Free tumor DNA, Liquid Biopsy
Brief summary
Circulating tumor DNA (ctDNA) carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Hepatocellular carcinoma (HCC) specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Use of 'liquid biopsy' by assessing circulating cell free DNA enables the clinician to offer targeted immunotherapy or signaling pathway inhibitors. It also offers a model to prove response to locoregional or immunotherapy therapy and predict tumor recurrence non-invasively.
Detailed description
Novelty: Mutation analysis may not only help identify cancer drivers, but they can also provide useful data to predict response to other treatment modalities such as immunotherapies, particularly immune checkpoint blockade. There is published data on liquid biopsy in India from oncology in the field of pulmonary and renal cancers, but these studies have not been done in cirrhosis or in HCC patients. Objectives In this project we hope to develop a biomarker panel which helps us prognosticate patients and tailor targeted therapy as per their genetic mutation landscape. The treatment options for advanced HCC are limited, and tissue biopsy is not routinely performed. Methods In this pilot project, we will analyze 30 patients with unresectable hepatocellular carcinoma, ineligible for liver transplantation, who will undergo locoregional therapy in the form of transarterial chemoembolization (TACE) or radioembolization (TARE) for tissue diagnosis of tumor tissue DNA and circulating tumor DNA. We will design personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing will be performed using cell-free DNA and paired primary tumor tissue DNA in order to create a non-invasive liquid biopsy for diagnosis and prognostication of HCC.
Interventions
DIAGNOSTIC_TESTCell Free DNA
Pre and post procedure plasma cell free DNA will be assessed for response to locoregional therapy
Sponsors
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Hepatocellular carcinoma BCLC stages B and C of all aetiology, unresectable * Age 18-70 years of either sex
Exclusion criteria
* Contemplating Hepatic resection or OLT * Refractory ascites * Severe Coagulation disorders prior to the procedure (PTI \<70% and Platelet count \< 80,000/mm3) * Hepato-Renal syndrome * Chronic Kidney Disease * Acute decompensation like Hepatic encephalopathy and variceal bleeding * Any known malignancy other than HCC * Life expectancy \< 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of exome sequencing of primary tumor tissue and cell-free DNA from plasma samples | 0, 90 days |
| Serial Quantification of ctDNA in plasma samples by means of real-time PCR post treatment | 90 days |
Secondary
| Measure | Time frame |
|---|---|
| Time to first recurrence (local or distant) diagnosed on follow up dynamic imaging. | 90 days |
| Mortality | 90 days |
Countries
India
Contacts
Primary ContactMadhumita Premkumar, MD DM
Backup ContactHarman Dhaliwal, MSc
Outcome results
None listed