Negative feedback of miR-29 family TET1 involves in hepatocellular cancer

Circulating tumor cells (CTCs) are valuable for diagnosis, monitoring therapy and prognosis in primary lung cancer. Herein, we evaluated the clinical significance of lung cancer CTCs in this study. Detection of CTCs was performed using epithelial cell adhesion molecule-independent enrichment and CD45 fluorescence in situ hybridization detection. CTCs ≥2/3.2 mL were considered as positive. The positive rates in primary lung cancer, benign lung disease and healthy control groups were 84, 0 and 4.2 %. CTCs count was significantly higher in lung cancer patients than healthy controls and benign lung disease, with an area under ROC curve of 0.917 (95 % confidence interval 0.855–0.979; p = 0.000) between lung cancer and nonmalignant diseases. CTCs count significantly increased with an increase in pathological stage with mean count of 2.3 ± 2.6 (stage I–II), 3.5 ± 3.3 (stage III) and 4.5 ± 4.3 (stage IV), respectively. The positive detection rate of CTCs for primary lung cancer diagnosis was higher than serum tumor markers. In total, 25 metastasis lung cancer patients participated in the follow-up. Changes in CTCs count after two cycles of chemotherapy were consistent with radiographic appearance. Moreover, CTCs count was better than serum tumor markers for monitoring chemotherapy response. Median progression-free survival (PFS) was 2.05, 3.25 and 8.348 months (p < 0.05) in group in which post-treatment CTCs count was increased, unchanged and decreased, respectively. Furthermore, PFS in patients whose post-treatment CTCs count increased or were unchanged accompanied by a baseline CTCs count <3 was significantly shorter than those whose post-treatment CTCs count decreased or was unchanged accompanied with baseline value ≥3 (1.85 vs. 8.22 months, p = 0.000). Therefore, CTCs are a reproducible indicator of disease status that may be superior to imaging.     

Clinical significance of circulating tumor cells in breast cancer patients

Circulating tumor cells (CTCs) are defined as tumor cells circulating in the peripheral blood of patients, shed from either the primary tumors or its metastases. Many techniques have been developed in the recent years to identify CTCs in breast cancer patients, and trials have proved the prognostic significance of CTCs. In this study, we validated the CTC detection method of combining cell filtration and laser scanning cytometry (LSC), which was highly reproducible with increased sensitivity and accuracy. In 134 non-metastatic breast cancer patients analyzed, HER2 was found to be the only primary tumor characteristics that correlated with the presence of CTCs. 85 patients with definitive stage information were selected for association study between the disease stages and CTC numbers. The detection rate and the number of CTCs were correlated with the disease stages. Moreover, assessment of CTCs in 92 metastatic breast cancer patients was found to be able to predict the efficacy of chemotherapy. Increase in CTC numbers was an independent prognostic factor for treatment outcomes. Our results suggested that CTC assessment could be an indication of the disease progression and analysis of the properties of CTCs is likely to provide new insights into the biology of breast cancer and contribute to defining novel treatments and better prediction of clinical outcomes.     

Apoptotic circulating tumor cells (CTCs) in the peripheral blood of metastatic colorectal cancer patients are associated with liver metastasis but not CTCs

Enumeration of circulating tumor cells (CTCs) by the CellSearch system provides prognostic information in metastatic colorectal cancer, regardless of metastatic site. We found that CTCs generally represent <1% of observed events with CellSearch analysis and adapted scoring criteria to classify other peripheral blood events. Examination of twenty two metastatic colorectal cancer patients'' blood revealed that patients with high CEA or liver metastases, but not lung or distant lymph node metastases, possessed significant numbers of apoptotic CTCs prior to treatment initiation by Fischer''s exact test. Six out of eleven patients with liver metastasis possessed apoptotic CTCs whereas one of nine patients with other metastases had measurable apoptotic CTCs. An elevated CTC number was not necessarily associated with apoptotic CTCs or CTC debris by Spearman''s correlation, suggesting the metastatic site rather than CTCs per se as contributing to the origin of these events.     

Detecting and phenotyping of aneuploid circulating tumor cells in patients with various malignancies

Circulating tumor cells (CTCs) have been exclusively studied and served to assess the clinical outcomes of treatments and progression of cancer. Most CTC data have mainly been derived from distinct cohorts or selected tumor types. In the present study, a total of 594 blood samples from 479 cases with 19 different carcinomas and 30 healthy samples were collected and analyzed by Subtraction enrichment method combined with immunostaining-fluorescence in situ hybridization (iFISH). Non-hematopoietic cells with aneuploid chromosome 8 (more than 2 copies) were regarded as positive CTCs. The results showed that none of CTCs was found in all 30 healthy samples. The overall positive rate of CTCs was 89.0% in diagnosed cancer patients (ranging from 75.0% to 100.0%). Average number of 11, 5, 8 and 4 CTCs per 7.5 mL was observed in lung cancer, liver cancer, renal cancer and colorectal cancer, respectively. Among 19 different carcinomas, the total number of CTCs, tetraploid chromosome 8, polyploid chromosome 8, CTM (Circulating tumor microemboli) and large CTCs in patients with stage Ⅲ and Ⅳ were statistically higher than patients with stage Ⅰ and Ⅱ (P < 0.05). Furthermore, EpCAM expression was more frequently found in most CTCs than vimentin expression, confirming that these CTCs were of epithelial origin. In addition, small and large CTCs were also classified, and the expression of vimentin was mostly observed in small CTCs and CTM. Our results revealed that there are higher numbers of CTCs, tetraploid, polyploid and large CTCs in patients with stage Ⅲ and Ⅳ, indicating that the quantification of chromosome ploidy performed by SE-iFISH for CTCs might be a useful tool to predict and evaluate therapeutic efficacy as well as to monitoring disease progression.     

Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications

The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.     

Secondary Circulating Tumor Cells (CTCs) but not Primary CTCs are Associated with the Clinico-Pathological Parameters in Chilean Patients With Colo-Rectal Cancer

Background: The aim of this study was to assess detection of circulating tumor cells (CTC) using anti-CEApre and post surgery in Chilean patients with colo-rectal cancer. Materials and Methods: The presence of CTCswas evaluated in 80 colorectal cancer patients pre and post surgery using standard immunocytochemistry andthe results were compared with findings for standard clinico-pathological parameters. Results: In patients presurgeryCEA (+) CTCs were frequently found, with no relation to tumor size or nodal status. After surgery, thepresence of CTCs was associated with such clinico-pathological parameters. The frequency of CTC detection innode positive patients did not change after surgery. In patients with metastasis there was also no change in thefrequency of CTC detection, and clusters of 3 or more CTCs were evident. Conclusions: Secondary CTCs areassociated with clinico-pathological parameters only after surgical removal of the primary tumor, and mightbe important in identifying patients at high risk of relapse. Primary CTCs detected before surgical removal arefrequently found, are not associated with the clinico-pathological parameters and might have a role in cancerscreening. These findings suggest the need for studies with a larger population of patients.     

Labour productivity loss caused by premature deaths associated with breast cancer: results from Spain over a 10-year period

Purpose

Several studies have provided evidence on the prognostic relevance of circulating tumor cells (CTCs) detected before and after chemotherapy regarding overall survival (OS) and progression-free survival (PFS) in early breast cancer (EBC). We provide data on the prevalence of CTCs 2 and 5 years after primary diagnosis in a cohort of patients with EBC.

Methods

The SUCCESS study is a multicenter, prospective, randomized trial comparing PFS in primary breast cancer patients undergoing one of two adjuvant chemotherapy regimens followed by 2 versus 5 years of treatment with zoledronate. CTCs from patients without signs of breast cancer recurrence were analyzed in peripheral blood using the FDA cleared CellSearch® System (Veridex, USA) 2 and 5 years after primary diagnosis.

Results

CTCs were detected at 2 and 5 years after primary diagnosis in 96 (16.7%) and 47 (8.2%) of the 574 patients, respectively. There were no associations between CTC status and patient and tumor characteristics or treatment regimens. In 442 (77.0%) patients, no CTCs were detected at either of the two time points, and in 11 patients (1.9%), CTCs were found at both 2 and 5 years after primary diagnosis. In 85 (14.8%) patients, CTCs were present 2 years after primary diagnosis but not after 5 years, while 36 (6.3%) patients had CTCs in their blood only at the 5-year follow-up.

Conclusions

In patients with EBC, CTCs can be detected even 5 years after primary diagnosis without clinical signs of disease recurrence.

     

Detection of circulating tumor cells in peripheral blood of heavily treated metastatic breast cancer patients

Background

Circulating tumor cells (CTCs) are detected in peripheral blood of breast cancer patients, and they may play an important role as a prognostic and predictive marker. We conducted this study to determine the presence of CTCs with the CellSearch System? and the clinical significance in treatment of metastatic breast cancer (MBC).

Method

Twenty-eight MBC patients were enrolled. These patients were followed by assessing CTCs, imaging studies, and serum tumor markers. Blood samples were collected before starting a new treatment and at the treatment evaluation period (2–3 months after starting chemotherapy). The cutoff for CTC level was 5.

Results

At baseline, 9 of 28 patients (32%) had ≥5 CTCs per 7.5 mL of blood. At the evaluation period, 5 of 23 patients (22%) had ≥5 CTCs. The baseline CTC number did not contribute to determine their overall survival (OS); however, CTCs at the evaluation period were available to predict their OS (p < 0.001). In two cases, both CTCs and tumor markers were available as predictors of treatment efficacy. In two other cases, although alterations of tumor markers might not reflect disease condition, CTC alteration corresponded to their condition. One patient who had multiple skeletal metastasis only, experienced a decrease in her CTCs in spite of tumor marker alteration.

Conclusions

We suggest that monitoring the number of CTCs may be helpful in predicting the efficacy of the treatment and the prognosis. CTCs might be especially useful with patients whose lesions are difficult to assess.     

Unresectable Colorectal Cancer Synchronous Metastases: How to Manage the Primary Tumor

In patients with newly diagnosed colorectal cancer, a significant proportion of patients will present with disseminated disease. In the presence of a symptomatic primary tumor, resection may be required to alleviate the symptoms of obstruction, bleeding, or perforation. Historically, resection of the primary asymptomatic tumor was advocated because a large portion of patients eventually developed symptoms or complications related to their primary tumors. Resection was followed by adjuvant chemotherapy with 5FU and survival was modest. However, with the improved response rates to the newer cytotoxic systemic therapies the role of prophylactic resection of the primary tumor in unresectable stage IV colorectal cancer has been questioned. Newer data suggest that routine palliative resection of the synchronous primary lesion should not be performed in the absence of symptoms. Several questions remain and ongoing prospective randomized trials will likely address many of the limitations of currently available literature.     

Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables.

BACKGROUND: The CellSearch System is a technique to detect circulating tumor cells (CTCs) in patients with cancer. Few data have been published concerning the role of CTCs detection by this method in colorectal cancer. The aim of this study was to correlate the presence of CTCs with the commonest clinical and morphological variables. PATIENTS AND METHODS: Blood samples were collected from 97 patients and 30 healthy volunteers. Quantification of CTCs in 7.5 ml of blood was carried out with the CellSearch System. The results were expressed as number of CTCs/7.5 ml and the cut-off of >or=2 CTCs/7.5 ml was chosen to define the test as positive. RESULTS: Positive CTCs were detected in 34 of 94 patients (36.2%). Correlation was not found among positive CTCs and location of primary tumor, increased carcinoembryonic antigen level, increased lactate dehydrogenase level or grade of differentiation. Only stage correlated with positive CTCs (20.7% in stage II, 24.1% in stage III and 60.7% in stage IV, P = 0.005). CONCLUSIONS: CTCs detection by CellSearch is a highly reproducible method that correlates with stage but not with other clinical and morphological variables in patients with colorectal cancer. Colon cancer tumor cells are detectable in all stages. Further studies are warranted.     

Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis

BackgroundCirculating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC).Patients and methodsForty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration.ResultsCTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category.ConclusionThe detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.     

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher''s exact test. Results: CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher''s Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.     

HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial

There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch^® assay and AdnaTest BreastCancer?. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = ?0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.     

Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer

The purpose of this study was to assess the impact of disseminated tumor cells (DTCs) on progression-free and overall survival (OS) in patients with metastatic breast cancer (MBC) and to compare it to simultaneous detection of circulating tumor cells (CTCs) from the blood in a subgroup. Disseminated tumor cells were identified in bone marrow (BM) aspirates by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology prior to the beginning of a new-line therapy. CTCs were enumerated by the CellSearch^® technology. BM was obtained from 178 patients with MBC; 64/178 (36 %) patients were DTC-positive. Disseminated tumor cells occurred more frequently in patients with visceral metastases (p = 0.020) and ≥2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts ≥5 CTCs/7.5 ml blood. There was no significant association between the DTC and CTC status. Univariate analysis revealed DTC detection as a significant predictor of poor OS (p < 0.001); median OS in DTC-negative versus DTC-positive patients was 52 [95 % confidence interval (CI) 38–67] versus 28 [95 % CI 19–37] months. Moreover, as described previously, patients with ≥5 CTCs/7.5 ml blood were at an increased risk of disease progression (p = 0.026) and death (p = 0.025). Disseminated tumor cells are predictors of poor prognosis in MBC, highlighting the role of tumor cell dissemination into the BM for breast cancer progression. The absence of a significant association between concurrent DTCs and CTCs suggests they might represent different aspects of systemic BC spread.     

Clinico-pathological correlation of serial measurement of circulating tumor cells in 24 metastatic colorectal cancer patients receiving chemotherapy reveals interpatient heterogeneity correlated with CEA levels but independent of KRAS and BRAF mutation

Background: The Veridex CellSearch is an FDA-approved technology for enumerating circulating tumor cells in blood samples of metastatic colorectal cancer mCRC) patients and has prognostic value. It is important to understand how counts of circulating tumor cells (CTCs), which are advocated to be tools for “liquid biopsy” of tumors, correlate with clinical and pathologic variables of significance in these patients. In this study, we have attempted to make such correlations along with evaluating how CTC counts change during the course of chemotherapy. Patients and methods: Following an IRB-approved protocol, blood samples were collected from 24 patients with mCRC along with relevant clinico-pathological data. Blood was collected at defined time-points both prior to as well as during the course of treatment with combination chemotherapy, and CTC counts were enumerated from7.5 ml of blood. Results: Seventeen out of 24 patients with mCRC showed a CTC count of 2 or less cells in 7.5 ml of blood at base-line assessment before chemotherapy while 7 patients showed 3 or more cells in 7.5 ml of blood at that point. A correlation was found between high carcino-embryonic antigen (CEA) levels and high CTC counts (P = 0.018) although it was also found that some patients had elevated CTCs without an elevated CEA. No correlation with the time interval between detection of primary tumor and appearance of secondary (metastatic) tumor(s) was found. CTC counts did not correlate with the presence of lung or liver metastases, i.e. a number of mCRC patients with lung or liver metastases had a count of zero CTCs at baseline. We also noted no correlation between CTC number and the status of KRAS or BRAF mutation. CTC counts dropped immediately after the start of chemotherapy in 11 out of 21 patients, and also reduced from the baseline at the end of chemotherapy in 5 out of 10 patients. Six of 7 patients who started with 3 or more CTCs in 7.5 ml at baseline also showed a final CTC reduction at the end of the therapy assessment. Conclusions: Analysis of circulating tumor cells may be of use in monitoring response to therapy in mCRC, either in combination with CEA monitoring or alone when CTCs are elevated but CEA level is not.     

Efficacy of postoperative adjuvant chemotherapy for colorectal cancer

We attempted postoperative adjuvant chemotherapy for stage II or III colorectal cancer. To investigate the efficacy of the adjuvant chemotherapy, we retrospectively reviewed all 293 colorectal cancer patients who underwent curative resection between 1990 and 1996 in Kurume University Hospital. The patients were divided into two groups according to whether or not they received postoperative adjuvant chemotherapy. Patients in Group 1 (n = 156) underwent resection followed by administration of oral fluorouracil. Some also received intravenous 5-FU or MMC after surgery. Patients in Group 2 (n = 95) underwent surgery alone. The disease-free survival rate in Group 1 was significantly higher than that in Group 2, but only for those with rectal cancer, with no significant difference for those with colon cancer. The results were also analyzed according to tumor stage, degree of lymphatic and venous invasion, and histological grading. Findings were similar between the two groups for those with stage II, stage IIIa, a low grade of lymphatic and venous invasion, and well-differentiated adenocarcinoma. Postoperative adjuvant chemotherapy in colorectal cancer might reduce the risk of recurrence, particularly in cases of rectal cancer. However, postoperative adjuvant chemotherapy was insufficient for those with highly advanced cancer or a biologically aggressive tumor.     

Thymidylate synthase expression in circulating tumor cells: A new tool to predict 5‐fluorouracil resistance in metastatic colorectal cancer patients

Thymidylate synthase (TYMS) is an important enzyme for 5‐fluorouracil (5‐FU) metabolism in metastatic colorectal cancer (mCRC) patients. The search for this enzyme in circulating tumor cells (CTCs) can be a powerful tool to follow‐up cancer patients. mCRC patients were enrolled before the beginning of 5‐FU‐based chemotherapy. The blood was filtered on Isolation by Size of Epithelial Tumor Cells (ISET), and the analysis of TYMS expression in CTCs was made by immunocytochemistry. Additionally, we verified TYMS staining in primary tumors and metastases from the same patients. There were included 54 mCRC patients and 47 of them received 5‐FU‐based chemotherapy. The median CTCs number was 2 per mL. We were not able to analyze immunocytochemistry in 13 samples (9 patients with absence of CTCs and 4 samples due to technical reasons). Therefore, TYMS expression on CTCs was analyzed in 34 samples and was found positive in 9 (26.5%). Six of these patients had tumor progression after treatment with 5‐FU. We found an association between CTC TYMS staining and disease progression (DP), although without statistical significance (P = 0.07). TYMS staining in primary tumors and metastases tissues did not have any correlation with disease progression (P = 0.67 and P = 0.42 respectively). Patients who had CTC count above the median (2 CTCs/mL) showed more TYMS expression (P = 0.02) correlating with worse prognosis. Our results searching for TYMS staining in CTCs, primary tumors and metastases suggest that the analysis of TYMS can be useful tool as a 5‐FU resistance predictor biomarker if analyzed in CTCs from mCRC patients.     

CIRCULATE-Japan: Circulating tumor DNA–guided adaptive platform trials to refine adjuvant therapy for colorectal cancer

Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor–positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both “de-escalation” and “escalation” trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.