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Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.

ABSTRACT: BACKGROUND:We aim to investigate the utility of serial gene mutation tracking for locally advanced CRC in those who underwent curative resection following neoadjuvant chemotherapy. METHODS:We prospectively collected 10 locally advanced CRC cases for which curative resection was performed following preoperative neoadjuvant chemotherapy. Tissues from the primary tumour, distant metastatic tumours, and blood plasma were obtained during serial treatment. Comprehensive mutation analysis of 47 cancer-associated genes was performed using a pre-designed gene panel and next-generation sequencing. RESULTS:All cases showed a partial response to neoadjuvant chemotherapy, and pathological R0 resection was accomplished. In primary tumours, non-synonymous mutations were detected at between 1 and 14 sites before chemotherapy and at between 1 and 2 sites after. Founder mutations were precisely detected in blood plasma and metastatic tumours during longitudinal treatment. CONCLUSIONS:Serial mutational analysis indicated that subclonal selection occurs during chemotherapy and that plasma can substitute for tumourous tissue in mutational analysis for drug selection and treatment decisions.

SUBMITTER: Sugimachi K

PROVIDER: S-EPMC6134007 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.

Sugimachi Keishi K Sakimura Shotaro S Kuramitsu Shotaro S Hirata Hidenari H Niida Atsushi A Iguchi Tomohiro T Eguchi Hidetoshi H Masuda Takaaki T Morita Masaru M Toh Yasushi Y Maehara Yoshihiko Y Suzuki Yutaka Y Mimori Koshi K

British journal of cancer 20180803 4

<h4>Background</h4>We aim to investigate the utility of serial gene mutation tracking for locally advanced CRC in those who underwent curative resection following neoadjuvant chemotherapy.<h4>Methods</h4>We prospectively collected 10 locally advanced CRC cases for which curative resection was performed following preoperative neoadjuvant chemotherapy. Tissues from the primary tumour, distant metastatic tumours, and blood plasma were obtained during serial treatment. Comprehensive mutation analysi ...[more]

PMID: 30072744

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Project description:BackgroundThe efficacy of neoadjuvant chemotherapy is closely related to the long-term prognosis of colorectal cancer (CRC) patients. Apparent diffusion coefficient (ADC) is an index in dynamic enhanced magnetic resonance imaging (MRI), reflecting the density of tumor cells. ADC has been shown to be related to the efficacy of neoadjuvant chemotherapy in other malignant tumors, but there is still a lack of relevant research in CRC patients.MethodsA total of 128 patients with CRC treated with neoadjuvant chemotherapy in The First Affiliated Hospital of Xiamen University from January 2016 to January 2017 were retrospectively collected. According to the response after neoadjuvant chemotherapy, the patients were divided into an objective response group (n=80) and a control group (n=48). The clinical characteristics and ADC levels of the two groups were compared, and the predictive value of ADC on the efficacy of neoadjuvant chemotherapy was analyzed. The patients were followed up for 5 years to observe the difference of survival rate between the two groups, and further analyzed the correlation between ADC and survival rate.ResultsCompared with the control group, the tumor size in the objective response group was significantly reduced (3.32±1.60 vs. 5.07±2.19 cm, P=0.000); ADC significantly increased (1.23±0.18 vs. 0.98±0.18 ×10-3 mm2/s, P=0.000); albumin significantly increased (39.32±4.14 vs. 37.46±4.18 g/L, P=0.016); the proportion of patients with poorly differentiated or undifferentiated tumor cells was significantly lower (51.25% vs. 72.92%, P=0.016); and the 5-year mortality decreased significantly (40.00% vs. 58.33%, P=0.044). ADC had the highest predictive value of objective response for locally advanced CRC patients after neoadjuvant chemotherapy, and the area under the curve (AUC) was 0.834 [95% confidence interval (CI): 0.765-0.903, P=0.000]; ADC had certain predictive value for the 5-year survival of locally advanced CRC patients, and the AUC was 0.778 (95% CI: 0.696-0.861, P=0.000). ADC >1.055×10-3 mm2/s, tumor size <4.1 cm, and moderately or well differentiated tumors were favorable factors for patients with locally advanced CRC to obtain objective response after neoadjuvant chemotherapy (P<0.05).ConclusionsADC could be used as a predictor of the efficacy of neoadjuvant chemotherapy in locally advanced CRC patients.

Project description:BackgroundSerum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.MethodsIn total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.ResultsPre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).ConclusionsCA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.

Dataset Information

Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.

Publications

Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.

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