Serum microRNAs to predict the response to nivolumab in patients with esophageal squamous cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14511-e14511 ◽  
Author(s):  
Kazuki Sudo ◽  
Ken Kato ◽  
Juntaro Matsuzaki ◽  
Junpei Kawauchi ◽  
Satoko Takizawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Linear Discriminant ◽  
Expression Levels

e14511 Background: A phase II study demonstrated that nivolumab (Nivo), a PD-1 inhibitor, had a meaningful activity for patients with esophageal squamous cell carcinoma. Although several biomarkers, including PD-L1 expression levels in tumor tissue, are explored to predict the efficacy of Nivo, further investigation is needed. Here we evaluated whether serum levels of microRNA (miRNA) could be a candidate of predictive markers. Methods: Among 65 patients who participated in the phase II study (JapicCTINo.142422) and received Nivo 3 mg/kg IV Q2W, 19 patients were treated at our institution. Patients were classified into responder and non-responder by investigators based on modified ir-RECIST. Serum samples were stored before and during treatment in the National Cancer Center Biobank. Comprehensive miRNA microarray analyses were performed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.), which was designed to detect 2565 miRNA expression levels. miRNA were compared between responders and non-responders using Fisher’s linear discriminant analysis, and then we calculated the area under curve (AUC) values of receiver operating characteristic curve. We explored the miRNA that showed AUC values of more than 0.8 and difference by 0.5 in the average log2 value of miRNA levels (log2miRNA) between responders and non-responders, and investigated their relation to progression-free survival using Kaplan-Meier curves and log-rank tests. Results: Among 19 patients, 5 responded (CR/PR, 1/4) to Nivo. We identified 3 miRNAs in the serum before treatment that were related to response to Nivo with AUC of 0.84 (log2miRNA of non-responder/responder: 13.16/12.47), 0.90 (8.65/10.20) and 0.81 (7.18/6.57), respectively. In the serum after the first treatment, 5 miRNAs were related to response to Nivo with AUC of 0.93 (11.93/11.09), 0.93 (11.87/11.13), 0.85 (7.92/8.53), 0.92 (6.61/5.82) and 0.93 (7.77/ 7.09), respectively. Among these 8 miRNAs, 4 miRNAs were significantly associated with progression-free survival. Conclusions: We identified miRNA candidates that could predict the response to Nivo. Further validation is warranted to confirm the results of our explorative research.

Phase II study of BKM120 in patients with advanced esophageal squamous cell carcinoma (EPOC1303).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4069-4069 ◽  
Author(s):  
Ken Kato ◽  
Toshihiko Doi ◽  
Takashi Kojima ◽  
Hiroki Hara ◽  
Shunji Takahashi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Clinical Activity ◽  
Primary Analysis

4069 Background: BKM120 is an oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, which showed promising activity in breast cancer and squamous cell carcinoma of head and neck. We prospectively investigated clinical activity, safety and biomarkers of BKM120 in advanced esophagus squamous cell carcinoma (ESCC). Methods: We conducted a multicenter phase II study of BKM120 monotherapy in patients with pretreated advanced ESCC. All the patients had a treatment history of fluoropyrimidine and platinum. BKM120 of 100 mg/day was orally administered in a 28-day cycle. A primary end-point was a disease control rate (DCR). Using Simon’s minimax two-stage design, total of 41 patients were required for primary analysis (promising DCR of 60%, non-promising one of 40%, one-sided alpha level of 10% and power of 90%). The response rate (RR), progression-free survival (PFS), overall survival (OS), and safety were also evaluated as secondary endpoints. Tumor samples for all the patients were required for gene alternation analysis in comprehensive genomic profiling assay (FoundationOne). Results: A total of 42 patients (median age, 62.5 years; performance status 0/1 = 28/14) were enrolled. One ineligible patient was excluded from primary analysis. Nineteen and two patients had SD and unconfirmed PR. DCR was 51.2% (95% CI, 35.1% to 67.1%), which met the primary endpoint of the study. Median PFS and OS was 2.0 months (95% CI, 1.8 to 3.2 months) and 9.0 months (95% CI, 6.4 to 11.7 months), respectively. Common grade 3 or 4 adverse events were anorexia, rash, hyponatremia, lipase increased, and abnormal hepatic function (including increased transaminase levels), which were profiles similar to previous studies of BKM120 monotherapy. No treatment-related deaths occurred. Further analyses of the gene alternation are ongoing. Conclusions: BKM120 monotherapy showed promising efficacy and mild toxicity profile in patients with pretreated advanced ESCC. BKM120 is worth evaluating in a further confirmatory study. Result of subgroup analyses with respect to gene alternation status will be presented. Clinical trial information: UMIN000011217.

scholarly journals A Radiomics Nomogram for Non-Invasive Prediction of Progression-Free Survival in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Ting Yan ◽  
lili liu ◽  
Meilan Peng ◽  
Zhenpeng Yan ◽  
Qingyu Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Validation Cohort ◽  
Progression Free Survival ◽  
Tnm Staging ◽  
Free Survival ◽  
Training Cohort ◽  
Radiomics Signature

Abstract Objectives: To construct a prognostic model for preoperative prediction based on computed tomography (CT) images of esophageal squamous cell carcinoma (ESCC). Methods: Radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) with high throughput radiomics features that extracted from the CT images of 272 patients (204 in training and 68 in validation cohort), who were pathologically confirmed ESCC. Multivariable logistic regression was adopted to build the radiomics signature and another predictive nomogram model, which was composed with radiomics signature, traditional TNM stage and clinical features. Then its performance was assessed by the calibration and decision curve analysis (DCA). Results: 16 radiomics features were selected from 954 to build a radiomics signature，which were significantly associated with progression-free survival (PFS) (p<0.001). The area under the curve (AUC) of performance was 0.891 (95% CI: 0.845-0.936) for training cohort and 0.706 (95% CI: 0.583-0.829) for validation cohort. The radscore of signatures’ combination showed significant discrimination for survival status in both two cohort. Kaplan-Meier survival curve further confirmed the radscore has a better prognostic performance in training cohort. Radiomics nomogram combined radscore with TNM staging showed significant improvement over TNM staging alone in training cohort (C-index, 0.802 vs 0.628; p<0.05), and it is the same with clinical data (C-index, 0.798 vs 0.660; p<0.05). Findings were confirmed in the validation cohort. DCA showed CT-based radiomics model will receive benefit when the threshold probability was between 0 and 0.9. Heat maps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric CT-based radiomics nomograms provided improved prognostic ability in ESCC.

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