Can Liquid Biopsies Predict Tumor Progression?

In an exploratory case of a patient with metastatic colorectal cancer, a hotspot panel of cancer-associated gene mutations was used to identify tumor-specific mutations. The results, which showed that liquid biopsies can reveal tumor heterogeneity and predict tumor progression, were published in Frontiers in Oncology.

Liquid biopsies are a minimally invasive technique for detecting tumor biomarkers such as circulating tumor cells, tumor microvesicles, and circulating tumor DNA (ctDNA) in plasma and other body fluids.

In this case presentation, a 57-year old man presented with metastatic sigmoid adenocarcinoma. Computed tomography (CT) showed hepatic nodules with peripheral contrast enhancement. Treatment included a laparoscopic sigmoidectomy with primary colorectal anastomosis, followed by palliative chemotherapy. CT imaging was done ever 2-3 months to evaluate the hepatic lesions. Carcinoembryonic antigen was evaluated at the time of diagnosis (145 mg/dl) and before commencement of the second-line treatment (1,678 mg/dl).

The patient underwent a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis. Five mutations--KRAS, TP53, RB1, ALK, and ERBB2--were detected in the ctDNA of six serial plasma samples. Only 2 mutations--KRAS and TP53--were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy, the gene frequency of both was below the detection limit suggesting that the lesions were responding to the treatment, but after 3 months of systemic treatment, the allele frequency was detectable in plasma, and increased thereafter. During the treatment period, ctDNA showed signs of disease progression while CT measurements suggested stable metastatic lesions, leading the authors to conclude that ctDNA analysis is a potential tool for monitoring treatment responsivity.  

“The RECIST imaging criteria is used universally to evaluate tumor response during and after systemic treatment for solid tumors. This criteria, which is related to tumor size changes, strongly correlates with clinical outcome (progression, symptoms, and death). However, it is becoming increasingly clear that other methods not based solely on tumor size should be developed and validated to improve our ability to evaluate treatment efficacy in oncology. The liquid biopsy technique represents one promising option,” the authors concluded.

 

--Kelsey Moroz

 

Reference

de Figueiredo Barros BD, Kupper BEC, Aguiar Junior S. Mutation Detection in Tumor-Derived Cell Free DNA Anticipates Progression in a Patient With Metastatic Colorectal Cancer. Front Oncol. 2018;8:306. doi: 10.3389/fonc.2018.00306. eCollection 2018.