Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma

Sheng Chieh Chan, Kai Ping Chang, Yu-Hua Dean Fang, Ngan Ming Tsang, Shu Hang Ng, Cheng Lung Hsu, Chun Ta Liao, Tzu Chen Yen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objectives/Hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Study Design: Retrospective cohort study. Methods: We examined 101 patients with primary NPC who underwent pretreatment 18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P =.0002), and uniformity (P =.001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P <.001). Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. Level of Evidence: 4 Laryngoscope, 127:E22–E28, 2017.

Original languageEnglish
Pages (from-to)E22-E28
JournalLaryngoscope
Volume127
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Fluorodeoxyglucose F18
Human Herpesvirus 4
Survival
DNA
Glycolysis
Neoplasms
Positron-Emission Tomography
Laryngoscopes
Recurrence
Entropy
Cohort Studies
Multivariate Analysis
Retrospective Studies
Tomography
Positron Emission Tomography Computed Tomography
Nasopharyngeal carcinoma

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology

Cite this

Chan, Sheng Chieh ; Chang, Kai Ping ; Fang, Yu-Hua Dean ; Tsang, Ngan Ming ; Ng, Shu Hang ; Hsu, Cheng Lung ; Liao, Chun Ta ; Yen, Tzu Chen. / Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma. In: Laryngoscope. 2017 ; Vol. 127, No. 1. pp. E22-E28.
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title = "Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma",
abstract = "Objectives/Hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Study Design: Retrospective cohort study. Methods: We examined 101 patients with primary NPC who underwent pretreatment 18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P =.0002), and uniformity (P =.001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P <.001). Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. Level of Evidence: 4 Laryngoscope, 127:E22–E28, 2017.",
author = "Chan, {Sheng Chieh} and Chang, {Kai Ping} and Fang, {Yu-Hua Dean} and Tsang, {Ngan Ming} and Ng, {Shu Hang} and Hsu, {Cheng Lung} and Liao, {Chun Ta} and Yen, {Tzu Chen}",
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Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma. / Chan, Sheng Chieh; Chang, Kai Ping; Fang, Yu-Hua Dean; Tsang, Ngan Ming; Ng, Shu Hang; Hsu, Cheng Lung; Liao, Chun Ta; Yen, Tzu Chen.

In: Laryngoscope, Vol. 127, No. 1, 01.01.2017, p. E22-E28.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma

AU - Chan, Sheng Chieh

AU - Chang, Kai Ping

AU - Fang, Yu-Hua Dean

AU - Tsang, Ngan Ming

AU - Ng, Shu Hang

AU - Hsu, Cheng Lung

AU - Liao, Chun Ta

AU - Yen, Tzu Chen

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N2 - Objectives/Hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Study Design: Retrospective cohort study. Methods: We examined 101 patients with primary NPC who underwent pretreatment 18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P =.0002), and uniformity (P =.001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P <.001). Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. Level of Evidence: 4 Laryngoscope, 127:E22–E28, 2017.

AB - Objectives/Hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Study Design: Retrospective cohort study. Methods: We examined 101 patients with primary NPC who underwent pretreatment 18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P =.0002), and uniformity (P =.001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P <.001). Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. Level of Evidence: 4 Laryngoscope, 127:E22–E28, 2017.

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