to be more reliable and sensitive at detecting tumor recurrence than
CEA. Diehl et al. measured ctDNA in patients after complete and
incomplete resections. Those patients with undetectable ctDNA
had 100% recurrence-free survival (RFS) at 2 years, compared to
less than 15% RFS for patients with detectable ctDNA. Frattini et al.
reported similar findings in a cohort of 70 CRC patients under-
going surgery. Their plasma DNA and CEA levels were followed for
16 months. Prior to surgery, circulating plasma DNA was elevated
in all patients, whereas only 30% of patients had an elevated CEA.
However, plasma DNA levels increased in all patients who ulti-
mately developed metastases or loco-regional relapse. On the con-
trary, CEA levels did not increase in all patients with recurrent
disease. The comparison revealed the sensitivity advantage of
plasma DNA than CEA.
For patients with stage II CRC, ctDNA is being evaluated in
the postoperative setting to detect disease recurrence. Preliminary
data of 190 patients demonstrate cancer recurrence in 5 of
6 patients with detectable ctDNA and 5 of 72 patients with unde-
tectable ctDNA [41]. Patients with detectable ctDNA had a shorter
recurrence-free survival (median 234 days vs. undefined, HR
23.09, P < 0.0001). For patients with stage II colon cancer
whose overall prognosis is good and the benefit of adjuvant che-
motherapy is limited, ctDNA might eventually be used to identify
patients with the greatest risk of recurrence. In addition to detec-
tion of recurrent disease, the presence of circulating tumor pro-
ducts may eventually guide adjuvant chemotherapy decisions [42].4.3 Guidance of
Targeted Drugs
Lung cancer is the leading cause of cancer-related death among
men and women in the world. Elucidation of molecular landscapes
of lung cancer is pivotal to guide treatment choices in both clinical
practice and trials [21]. The inherent molecular heterogeneity and
dynamic evolution of cancer genomes are not properly revealed by
tissue biopsy. Evaluation of tumor-derived cfDNA in plasma offers
the potential to overcome some barriers such as difficult anatomical
locations, dangerous tumors surrounding major vessels or in elo-
quent regions of the brain, and difficulty in continuous monitoring.
Noninvasive liquid biopsy technology is useful for rapid identifica-
tion of tumor-specific mutations in NSCLC. Detection of target-
able tumor-specific mutation in the blood may facilitate
personalized treatment selection for individual patients with lung
cancer [28].4.3.1 EGFR TKIs NSCLC is the most common type of lung cancer. NSCLC tumors
may shed tumor DNA into a patient’s blood, making it possible to
detect specific mutations in blood samples. The US FDA and the
European Medicines Agency approved blood-based tests to detect
EGFR gene mutations in the NSCLC patients if no tissue sample is
available [43]. NSCLC patients harboring the somatic mutations of
52 Jun Li et al.