TY - JOUR
T1 - Development and validation of a molecular tool to predict pathologic complete response in esophageal adenocarcinoma
AU - Qian, David C.
AU - Lefferts, Joel A.
AU - Zaki, Bassem I.
AU - Brickley, Elizabeth B.
AU - Jackson, Christopher R.
AU - Andrici, Juliana
AU - Sriharan, Aravindhan
AU - Lisovsky, Mikhail
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Pathologic complete response (pCR) to neoadjuvant chemoradiation for locally advanced esophageal adenocarcinoma (EAC) confers significantly improved survival. The ability to infer pCR may spare esophagectomy in some patients. Currently, there are no validated biomarkers of pCR. This study sought to evaluate whether a distinct signature of DNA copy number alterations (CNA) can be predictive of pCR in EAC. Pretreatment biopsies from 38 patients with locally advanced EAC (19 with pCR and 19 with pathologic partial/poor response) were assessed for CNA using OncoScan assay. A novel technique was employed where within every cytogenetic band, the quantity of bases gained by each sample was computed as the sum of gained genomic segment lengths weighted by the surplus copy number of each segment. A threefold cross-validation was used to assess association with pCR or pathologic partial/poor response. Forty patients with locally advanced EAC from The Cancer Genome Atlas (TCGA) constituted an independent validation cohort. Gains in the chromosomal loci 14q11 and 17p11 were preferentially associated with pCR. Average area under the receiver operating characteristic curve (AUC) for predicting pCR was 0.80 among the threefold cross-validation test sets. Using 0.3 megabases as the cutoff that optimizes trade-off between sensitivity (63%) and specificity (89%) in the discovery cohort, similar prediction performance for clinical and radiographic response was demonstrated in the validation cohort from TCGA (sensitivity 61%, specificity 82%). Copy number gains in the 14q11 and 17p11 loci may be useful for prediction of pCR, and, potentially, personalization of esophagectomy in EAC.
AB - Pathologic complete response (pCR) to neoadjuvant chemoradiation for locally advanced esophageal adenocarcinoma (EAC) confers significantly improved survival. The ability to infer pCR may spare esophagectomy in some patients. Currently, there are no validated biomarkers of pCR. This study sought to evaluate whether a distinct signature of DNA copy number alterations (CNA) can be predictive of pCR in EAC. Pretreatment biopsies from 38 patients with locally advanced EAC (19 with pCR and 19 with pathologic partial/poor response) were assessed for CNA using OncoScan assay. A novel technique was employed where within every cytogenetic band, the quantity of bases gained by each sample was computed as the sum of gained genomic segment lengths weighted by the surplus copy number of each segment. A threefold cross-validation was used to assess association with pCR or pathologic partial/poor response. Forty patients with locally advanced EAC from The Cancer Genome Atlas (TCGA) constituted an independent validation cohort. Gains in the chromosomal loci 14q11 and 17p11 were preferentially associated with pCR. Average area under the receiver operating characteristic curve (AUC) for predicting pCR was 0.80 among the threefold cross-validation test sets. Using 0.3 megabases as the cutoff that optimizes trade-off between sensitivity (63%) and specificity (89%) in the discovery cohort, similar prediction performance for clinical and radiographic response was demonstrated in the validation cohort from TCGA (sensitivity 61%, specificity 82%). Copy number gains in the 14q11 and 17p11 loci may be useful for prediction of pCR, and, potentially, personalization of esophagectomy in EAC.
KW - copy number alterations
KW - esophageal adenocarcinoma
KW - neoadjuvant chemoradiation
KW - pathologic complete response
KW - The Cancer Genome Atlas
UR - http://www.scopus.com/inward/record.url?scp=85144587505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144587505&partnerID=8YFLogxK
U2 - 10.1093/dote/doac035
DO - 10.1093/dote/doac035
M3 - Article
C2 - 35758407
AN - SCOPUS:85144587505
SN - 1120-8694
VL - 35
JO - Diseases of the Esophagus
JF - Diseases of the Esophagus
IS - 12
M1 - doac035
ER -