scholarly journals Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer

2020 ◽  
Vol 11 (5) ◽  
pp. 1065-1077
Author(s):  
Wei Zhao ◽  
Lige Qiu ◽  
Huajiang Liu ◽  
Ying Xu ◽  
Meixiao Zhan ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15712-e15712
Author(s):  
Fumiaki Watanabe ◽  
Koichi Suzuki ◽  
Sawako Tamaki ◽  
Hideki Ishikawa ◽  
Nao Kakizawa ◽  
...  

e15712 Background: Liquid biopsy enables the detection of circulating tumor DNA (ctDNA) levels, including KRAS-mutated ctDNA, which is considered a predictive biomarker for pancreatic cancer. This study aimed to evaluate the significance of sequential KRAS ctDNA assessments in longitudinal monitoring. Methods: A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS ctDNA levels was determined by droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and evaluating therapeutic responses to chemotherapy. Results: In 39 patients who underwent surgery for potentially resectable tumors, sequential assessments of KRAS ctDNA in longitudinal monitoring was significantly associated with prognosis ( P < 0.001). In 39 patients who did not undergo surgery, sequential assessments of KRAS ctDNA was a predictive factor for prognosis ( P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA in longitudinal monitoring was the only independent prognostic factor regardless of tumor resection ( P< 0.001). Longitudinal monitoring revealed the significance of sequential assessments of KRAS ctDNA within a short period. The presence of KRAS ctDNA in sequential assessments within 1 year after surgery showed significant association with prognosis irrespective of recurrence ( P< 0.001). The presence of KRAS ctDNA in sequential assessments within 6 months was significantly correlated with therapeutic responses in the first line chemotherapy ( P< 0.001). Conclusions: Our study showed for the first time that sequential assessments of KRAS ctDNA levels within a short period enabled the prediction of prognosis and therapeutic response in patients with pancreatic cancer.


2017 ◽  
Vol 28 ◽  
pp. ii10-ii11
Author(s):  
F. Passiglia ◽  
A. Perez ◽  
A. Listì ◽  
M. Castiglia ◽  
E. Musso ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Ying Jia ◽  
Yufei Xing ◽  
Meitian Yang

Objective. To explore the efficacy of sorafenib combined with interventional therapy on primary liver cancer (PLC) patients and its effect on serum AFP, VEGF, and GGT. Methods. 120 PLC patients admitted to our hospital from January 2019 to January 2020 were selected as the research object and divided into group A and group B according to the admission order, with 60 cases each. Interventional therapy was performed to both groups, and sorafenib was given to group A additionally to compare their treatment effect, survival, adverse reaction rate (ARR), and serum AFP, VEGF, and GGT levels. Results. After treatment, group A obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) ( p < 0.05 ), higher one-year survival rate and two-year survival rate ( p < 0.05 ), lower ARR of skin reactions, gastrointestinal reactions, hepatorenal reactions, and hyperbilirubinemia ( p < 0.05 ), and lower serum AFP, VEGF, and GGT levels ( p < 0.001 ). Conclusion. The combination of sorafenib and interventional therapy can inhibit the growth and migration of PLC, improve the immune function, prolong the survival period of patients, and lower ARR, so it should be promoted in practice.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4593-4593
Author(s):  
Ledu Zhou ◽  
Ying Xu ◽  
Dong Wang ◽  
Ke Ye ◽  
Liang Xiao ◽  
...  

4593 Background: Resection is a major method for early-stage liver cancer patients. Unfortunately, there still a few patients with post-operation recurrences. Circulating tumor DNA (ctDNA) had been reported as a biomarker in reflecting tumor load and treatment efficacy in some cancer species. Here, we report an application of ctDNA in the perioperative period of liver cancer using targeted sequencing with a 1021-gene panel. Methods: 97 patients diagnosed with liver cancer were enrolled in this study. Postoperative peripheral blood samples were collected within 7 days after surgery and analyzed using hybridization capture based NGS ERSeq method from all patients. Whether a mutant gene was detected in the peripheral blood was defined as ctDNA(+) and ctDNA(-), respectively. Results: Multivariate Cox analysis showed that the post-operation ctDNA was an independent poor prognostic predictor (AFP, RR: 1.0002, 95% Cl: 1.0001-1.0002; ctDNA, RR: 3.738, Cl: 1.872-7.691). 21 patients were ctDNA(+), and all of them had recurrenced (21/21, 100%), while 76 patients were ctDNA(-), and only 12 (12/76, 15.8%) patients had recurrenced. The median disease-free survival time was 5.0 months in ctDNA(+) group and the ctDNA(-) group had not reach the median time (Log-rank test, P < 0.0001). ctDNA combined with AFP would effectively predict the prognosis of patients after surgery. AFP(H) ( > = 400 ng/mL) and ctDNA(+) patients have the worst prognosis and all of the patients had relapsed, while AFP(L) ( < 400 ng/mL) and ctDNA(-) patients had the best prognosis, with less than 20% of patients had relapsed (Log-rank test, P < 0.0001). The median disease-free survival time was 2.0, 6.0 and 7.0 months in ctDNA(+)-AFP(H) (n = 8), ctDNA(-)-AFP(H) (n = 30) and ctDNA(+)-AFP(L) (n = 13) groups, respectively, while ctDNA(-)-AFP(L) group (n = 46) had not reach the median time statistically (Log-rank test, P = 0.0364). Conclusions: In summary, Perioperative ctDNA detection has great potential value clinically, and it also suggests that patients with positive ctDNA after surgery should receive some adjuvant treatments as soon as possible to improve the survival time.


2018 ◽  
Vol 29 ◽  
pp. viii29
Author(s):  
A. Bernard-Tessier ◽  
E. Jeannot ◽  
D. Guenat ◽  
M. Michel ◽  
C. Proudhon ◽  
...  

2021 ◽  
pp. 1758-1767
Author(s):  
Iris van 't Erve ◽  
Nina J. Wesdorp ◽  
Jamie E. Medina ◽  
Leonardo Ferreira ◽  
Alessandro Leal ◽  
...  

PURPOSE Somatic KRAS mutations occur in approximately half of the patients with metastatic colorectal cancer (mCRC). Biologic tumor characteristics differ on the basis of the KRAS mutation variant. KRAS mutations are known to influence patient prognosis and are used as predictive biomarker for treatment decisions. This study examined clinical features of patients with mCRC with a somatic mutation in KRAS G12, G13, Q61, K117, or A146. METHODS A total of 419 patients with colorectal cancer with initially unresectable liver-limited metastases, who participated in a multicenter prospective trial, were evaluated for tumor tissue KRAS mutation status. For the subgroup of patients who carried a KRAS mutation and were treated with bevacizumab and doublet or triplet chemotherapy (N = 156), pretreatment circulating tumor DNA levels were analyzed, and total tumor volume (TTV) was quantified on the pretreatment computed tomography images. RESULTS Most patients carried a KRAS G12 mutation (N = 112), followed by mutations in G13 (N = 15), A146 (N = 12), Q61 (N = 9), and K117 (N = 5). High plasma circulating tumor DNA levels were observed for patients carrying a KRAS A146 mutation versus those with a KRAS G12 mutation, with median mutant allele frequencies of 48% versus 19%, respectively. Radiologic TTV revealed this difference to be associated with a higher tumor load in patients harboring a KRAS A146 mutation (median TTV 672 cm3 [A146] v 74 cm3 [G12], P = .036). Moreover, KRAS A146 mutation carriers showed inferior overall survival compared with patients with mutations in KRAS G12 (median 10.7 v 26.4 months; hazard ratio = 2.5; P = .003). CONCLUSION Patients with mCRC with a KRAS A146 mutation represent a distinct molecular subgroup of patients with higher tumor burden and worse clinical outcomes, who might benefit from more intensive treatments. These results highlight the importance of testing colorectal cancer for all KRAS mutations in routine clinical care.


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