TY - JOUR
T1 - Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma
AU - Koyuncu, Can F.
AU - Lu, Cheng
AU - Bera, Kaustav
AU - Zhang, Zelin
AU - Xu, Jun
AU - Toro, Paula
AU - Corredor, German
AU - Chute, Deborah
AU - Fu, Pingfu
AU - Thorstad, Wade L.
AU - Faraji, F.
AU - Bishop, Justin A.
AU - Mehrad, Mitra
AU - Castro, Patricia D.
AU - Sikora, Andrew G.
AU - Thompson, Lester D.R.
AU - Chernock, R. D.
AU - Lang Kuhs, Krystle A.
AU - Luo, Jingqin
AU - Sandulache, Vlad
AU - Adelstein, David J.
AU - Koyfman, Shlomo
AU - Lewis, James S.
AU - Madabhushi, Anant
N1 - Publisher Copyright:
© 2021, American Society for Clinical Investigation.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - BACKGROUND. Patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.
AB - BACKGROUND. Patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.
UR - http://www.scopus.com/inward/record.url?scp=85104191246&partnerID=8YFLogxK
U2 - 10.1172/JCI145488
DO - 10.1172/JCI145488
M3 - Article
C2 - 33651718
AN - SCOPUS:85104191246
SN - 0021-9738
VL - 131
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 8
M1 - e145488
ER -