scholarly journals Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Feng ◽  
Nan Jia ◽  
Haining Jiao ◽  
Jun Chen ◽  
Yan Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Tumor Recurrence ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Free Survival ◽  
Tumor Relapse ◽  
Disease Free ◽  
Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

scholarly journals Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

2020 ◽  
Author(s):  
Weiwei Feng ◽  
Nan Jia ◽  
Hai-ning Jiao ◽  
Jun Chen ◽  
Yan Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Tumor Recurrence ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Free Survival ◽  
Tumor Relapse ◽  
Disease Free ◽  
Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC.Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival.Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4.Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

Circulating tumor DNA analysis to detect minimal residual disease and predict recurrence in patients with resectable pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16799-e16799
Author(s):  
Liu Yang ◽  
Jiahong Jiang ◽  
Song Ye ◽  
Yaping Xu ◽  
Dongsheng Huang
Keyword(s):  
Minimal Residual Disease ◽  
Somatic Mutations ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Free Survival ◽  
Disease Free ◽  
Tumor Dna ◽  
Minimal Residual

e16799 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death, partly due to the high recurrence rates for patients with resectable PDAC. Current postoperative surveillance methods including monitoring of clinical symptoms, tumor markers and CT imaging, lack sensitivity and specificity to identify minimal residual disease (MRD). Methods: We investigated whether the detection of circulating tumor DNA (ctDNA) could identify MRD and predict relapse in postoperative patients with PDAC. In this study, we performed panel-captured sequencing to detect somatic mutations. Matched tissue samples were obtained to verify mutation. Results: A total of 27 patients and 65 plasma samples were included. Among the somatic mutations, KRAS and TP53 were the most recurrent genes in both tissue and plasma samples. The detectable rate of ctDNA increased with the stage of PDAC. The maximal variant allele fraction (VAF) of ctDNA had a positive correlation with tumor largest diameter (p = 0.0101). Patients with ctDNA-positive status postoperatively had a markedly reduced disease-free survival (DFS) compared to those with ctDNA-negative status (HR, 5.20; p = 0.019). Positive vascular invasion significantly influenced disease-free survival (DFS) (p = 0.036), and positive postoperative ctDNA status was an independent prognostic factor for DFS (HR = 3.60; 95% CI, 1.15-11.28; p = 0.028). Conclusions: Postoperative ctDNA detection provides strong evidence of MRD and identifies patients with a high risk of relapse. ctDNA detection is a promising approach for personalized patient management during postoperative follow-up.

scholarly journals Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study

Tumor Biology ◽  
2020 ◽  
Vol 42 (5) ◽  
pp. 101042832091919 ◽  
Author(s):  
Mariana Cartaxo Alves ◽  
Fernando Luiz Affonso Fonseca ◽  
Alayne Magalhães Trindade Domingues Yamada ◽  
Lílian Arruda do Rego Barros ◽  
André Lopes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Early Response ◽  
Circulating Tumor Dna ◽  
Free Survival ◽  
Disease Free ◽  
Tumor Dna

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

Perioperative circulating tumor DNA analysis to predict patient prognosis in liver cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4593-4593
Author(s):  
Ledu Zhou ◽  
Ying Xu ◽  
Dong Wang ◽  
Ke Ye ◽  
Liang Xiao ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Survival Time ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Rank Test ◽  
Free Survival ◽  
Log Rank Test ◽  
Post Operation ◽  
Disease Free ◽  
Tumor Dna

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.

Circulating tumor DNA as a promising biomarker of relapse risk for stage II-III colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4079-4079
Author(s):  
Gong Chen ◽  
Feng Wang ◽  
Jun-Jie Peng ◽  
San-Jun Cai ◽  
Ke-Feng Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Free Survival ◽  
Colorectal Cancer Patients ◽  
Disease Free ◽  
Tumor Dna

4079 Background: About 30-50% colorectal cancer patients undergoing a curative resection will experience disease recurrence ultimately. Early detection of recurrence is of great significance for improving the prognosis of colorectal cancer patients. Circulating tumor DNA (ctDNA) has been suggested to be a promising biomarker for postoperative surveillance and prognosis prediction in various cancers including colorectal cancer. However, its performance in predicting early recurrence of colorectal cancer as well as appropriate testing procedures still needs large-scale prospective studies to evaluate. Methods: A total of 246 patients with stage II-III colorectal cancer and underwent curative resection from three clinical centers of China were enrolled in this multicenter prospective cohort study. Tissue samples as well as serial plasma samples before surgery, 7 days and 6 months after surgery and 3 months interval afterwards until recurrence were collected, and subjected to deep targeted-panel sequencing containing 425 cancer-related genes. ctDNA baseline genomic alterations and dynamic changes were analyzed. Its performance in predicting early recurrence was evaluated and compared with other clinical routine investigations, including serum biomarkers CEA and CA199, and CT examination. Results: The ctDNA positive rates at baseline (before surgery) and 7 days after surgery were 72.9% and 18.1% respectively. Among 199 patients with complete survival data, 18 patients were recurrent during follow up period with a median disease-free survival of 280.5 days (114-461 days). At baseline, high clinical stage (p = 0.035), and PTEN mutation (p = 0.009) were significantly associated with increased recurrent risk; while APC mutation (p = 0.04) predicted a decreased recurrent risk. Detection of ctDNA 7 days after surgery [HR: 5.9 (1.94-17.97); p = 0.0004] or any time point before clinical recurrence [HR: 6.14 (2.3-16.38); p < 0.0001] was associated with a significantly higher recurrent risk, and the HR increased accordingly with ctDNA mutation level. In multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathological risk factors. CEA status was not significantly (p > 0.4) associated with disease-free survival. A risk scoring model comprising of clinical variables and ctDNA detection after surgery was constructed and can predict 18-month recurrence with an AUC of 0.77. Conclusions: ctDNA is a promising marker of risk stratification, and early relapse detection in resected stage II/III CRC patients. Clinical trial information: NCT03312374 .

Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival in Patients Affected by High-risk Endometrial Cancer

2018 ◽  
Vol 28 (3) ◽  
pp. 505-513 ◽  
Author(s):  
Violante Di Donato ◽  
Valentina Iacobelli ◽  
Michele Carlo Schiavi ◽  
Vanessa Colagiovanni ◽  
Irene Pecorella ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Myometrial Invasion ◽  
Depth Of Invasion ◽  
Prognostic Impact ◽  
Ki 67 ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
Disease Free

ObjectivesThe aim of this study was to evaluate the immunohistochemical (IHC) expression of Ki-67, estrogen receptors α (ERsα), and progesterone receptors (PRs) in high-risk endometrial cancer patients and to assess their prognostic impact.Methods/MaterialsImmunohistochemical expression of Ki-67, ERsα, and PRs was evaluated in primary untreated endometrial cancer. The correlation among IHC staining and risk factors of recurrence such as age, Federation International of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread was assessed.ResultsEighty-two patients were available for the analysis. Mean ± SD age was 65.05 ± 10.48 years. The IHC assessment revealed a lack of ERα in 46.3% and of PR in 48.7% as well as a high Ki-67 in 31.7%. Loss of ERα and PR was associated with a significant higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a deeper myometrial invasion. Analysis of the interrelationship between receptor immunonegativity revealed a relevant association of ERα immunolocalization with PR and with a high Ki-67 expression. The present study also showed that loss of ERα (P = 0.003), advanced Federation International of Gynecology and Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent prognostic factors of a shorter disease-free survival. Importantly, loss of ERα, loss of PR, and a high Ki-67 were correlated with a higher incidence of distant recurrence.ConclusionsA systematic immunohistochemistry should be a key step in the therapeutic algorithm and could contribute to the identification of high-risk tumors.

BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Bryan P. Schneider ◽  
Guanglong Jiang ◽  
Tarah J. Ballinger ◽  
Fei Shen ◽  
Christopher Chitambar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free ◽  
Versus Treatment ◽  
Tumor Dna

PURPOSE Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.

scholarly journals HE4 is superior to CA125 in the detection of recurrent disease in high-risk endometrial cancer patients

Tumor Biology ◽  
2018 ◽  
Vol 40 (2) ◽  
pp. 101042831875710 ◽  
Author(s):  
Karin Abbink ◽  
Petra LM Zusterzeel ◽  
Anneke J Geurts-Moespot ◽  
Antonius E van Herwaarden ◽  
Johanna MA Pijnenborg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Confidence Interval ◽  
Cancer Patients ◽  
Recurrent Disease ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Objective: To date, biomarkers are not routinely used in endometrial cancer diagnosis, prognosis, and follow-up. The purpose of this study was to evaluate whether serum HE4 was related to clinicopathological risk factors and outcome. Second, the role of serum HE4 and CA125 was assessed as indicator for recurrent disease during follow-up. Methods: A total of 174 patients with endometrial cancer between 1999 and 2009 were selected for this retrospective study. Serum HE4 and CA125 were analyzed at primary diagnosis, during follow-up, and at the time of recurrence. Correlations with clinicopathological factors were studied by univariate and multivariate survival analyses. Lead time was calculated in order to determine which serum marker was elevated prior to clinical detection of recurrent disease. Results: Serum levels of HE4 and CA125 were significantly associated with high tumor grade, myometrial invasion, lymph node involvement, and advanced stage (p < 0.01). HE4 was an independent prognostic factor for reduced disease-free survival and overall survival with hazard ratios of 2.96 (95% confidence interval: 1.18–7.99) and 3.27 (95% confidence interval: 1.18–9.02), respectively. At recurrence, 75% of the patients had an elevated HE4 compared to 54% with an elevated CA125. HE4 levels were more frequently elevated in patients with distant metastasis compared to local recurrences, 67% and 37%, respectively. Serum HE4 detected a recurrence with a median of 126 days earlier than clinical confirmation. Conclusion: Elevated serum HE4 is an independent risk factor for reduced disease-free survival and overall survival. HE4 seems to be superior to CA125 in the detection of recurrent disease during follow-up, mainly in high-risk endometrial cancer patients who are more prone to distant metastasis.

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