Prognostic significance of the intratumoral heterogeneity of <sup>18</sup>F‐FDG uptake in oral cavity cancer

Kwon, Soo Hyun; Yoon, Joon-Kee; An, Young‐Sil; Shin, Yoo Seob; Kim, Chul‐Ho; Lee, Dong Hoon; Jo, Kyung Sook; Lee, Su Jin

doi:10.1002/jso.23703

Cited by 40 publications

(29 citation statements)

References 27 publications

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“…There is a growing interest in evaluating intra-tumoral heterogeneity by using FDG-PET with different parameters, such as textural analysis 31 , coefficient of variance (COV) 32 , cumulative SUV-volume histograms (CSH) 33 , the area under the CSH (AUC–CSH) 25 , fractal analysis 34,35 or heterogeneity factors 17 . To date, several studies have investigated the association between metabolic intra-tumoral heterogeneity of FDG uptake and patient's outcomes in several malignant tumours 36-38 including head and neck cancers 17,39 .…”

Section: Discussionmentioning

confidence: 99%

“…Investigators found that HF was an independent predictor of overall survival (p = 0.002); patients with HI < −0.13 showed a worse prognosis than those with HF ≥ −0.13 (p = 0.005) 39 . Similarly, Yang et al explored the utility of pre-treatment FDG-PET tumor heterogeneity in 40 patients with locally advanced nasopharyngeal carcinoma, concluding that lower tumor heterogeneity indexes (HI), calculated by dividing SUV max by SUV mean , significantly predicted progression-free-survival and overall survival 17 .…”

Section: Discussionmentioning

confidence: 99%

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Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Mena

Taghipour

Sheikhbahaei

et al. 2017

Clinical Nuclear Medicine

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Objective To evaluate the impact of intra-tumoral metabolic heterogeneity and quantitative FDG-PET/CT imaging parameters for predicting patient outcomes in primary oropharyngeal squamous cell cancer (OPSCC). METHOD AND MATERIALS We retrospective investigated 105 patients with HPV-positive OPSCC. Maximum standardized uptake value (SUVmax,), and metabolic tumor volume (MTV)were measured for the primary tumors and when available for the metastatic sites. Primary tumor intra-tumoral metabolic heterogeneity was calculated as the area under a cumulative SUV-volume Histograms curve (AUC-CSH). The median follow-up time was 35.4 months (range 3-92 months). Outcome endpoint was event free survival (EFS). Kaplan–Meier survival plots and Cox regression analyses were performed. RESULTS Of the 105 patients included, 19 patients relapsed and 11 deceased during the study period. AUC-CSH indexes were associated with EFS using PET gradient-based (p=0.034) and 50%-Threshold (p=0.02) segmentation methods, on multivariate analysis. Kaplan–Meier survival analysis using optimum cutoff of 16.7 SUVmax and 12.7 ml total MTV were significant predictors of EFS. Combining SUVmax and AUC-CSH index in three subgroups, patients with higher intra-tumoral heterogeneity and higher SUVmax were associated with worse outcome (log-rank p=0.026). Similarly, patients with higher intra-tumoral heterogeneity tumors and higher MTV had worse prognosis (log-rank, p= 0.022). CONCLUSION Intra-tumoral metabolic heterogeneity using FDG-PET was a prognostic factor for EFS in patients with primary HPV (+) OPSCC. The combined predictive effect of FDG avidity, metabolic tumor burden and intra-tumoral heterogeneity provided prognostic survival information in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Mena

Taghipour

Sheikhbahaei

et al. 2017

Clinical Nuclear Medicine

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“…To a limited degree, more complex analytics that explore the association of imaging features with oncologic outcomes have also been investigated, as these may be less dependent on the dose and timing of radiotracer administration (El Naqa et al 2009, Kwon et al 2014, Apostolova et al 2014). Although it appears that these individual imaging metrics are predictive to some degree for patient outcomes, they may not have sufficient predictive power to be clinically useful.…”

Section: Introductionmentioning

confidence: 99%

Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics

et al. 2017

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In this study, we investigate the use of imaging feature-based outcomes research (“radiomics”) combined with machine learning techniques to develop robust predictive models for the risk of all-cause mortality (ACM), local failure (LF), and distant metastasis (DM) following definitive chemoradiation therapy (CRT). One hundred seventy four patients with stage III-IV oropharyngeal cancer (OC) treated at our institution with CRT with retrievable pre- and post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were identified. From pre-treatment PET scans, 24 representative imaging features of FDG-avid disease regions were extracted. Using machine learning-based feature selection methods, multiparameter logistic regression models were built incorporating clinical factors and imaging features. All model building methods were tested by cross validation to avoid overfitting, and final outcome models were validated on an independent dataset from a collaborating institution. Multiparameter models were statistically significant on 5-fold cross validation with the area under the receiver operating characteristic curve (AUC)=0.65 (p=0.004), 0.73 (p=0.026), and 0.66 (p=0.015) for ACM, LF, and DM, respectively. The model for LF retained significance on the independent validation cohort with AUC=0.68 (p=0.029) whereas the models for ACM and DM did not reach statistical significance, but resulted in comparable predictive power to the 5-fold cross validation with AUC=0.60 (p=0.092) and 0.65 (p=0.062), respectively. In the largest study of its kind to date, predictive features including increasing metabolic tumor volume, increasing image heterogeneity, and increasing tumor surface irregularity significantly correlated to mortality, LF, and DM on 5-fold cross validation in a relatively uniform single-institution cohort. The LF model also retained significance in an independent population.

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“…However, the computing method of linear regression slope of MTV varied among different researchers, and it needs more data to process [18,35,36]. The textural analysis and deep learning are more complex, which demand special workstation and professionals, and they are not feasible integrated into clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that the intratumoral heterogeneity derived from PET/CT can serve as a prognostic biomarker for treatment outcome in pancreatic cancer [18], uterine leiomyosarcoma [20], head and neck squamous cell carcinoma [23], esophageal cancer [33], oral cavity cancer [35], and epithelial ovarian cancer [36]. Our results showed that the HI of the maximal neck lymph node was significantly associated with the long-term PFS in patients with primary NPC (HR, 3.23; 95% CI, 1.22-8.54; p=0.018).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Validation of a Nomogram with Intratumoral Heterogeneity Derived from 18F-FDG PET/CT for Predicting Individual Conditional Risk of 5-Year Recurrence before Initial Treatment of Nasopharyngeal Carcinoma

Song

et al. 2019

Preprint

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ObjectivesIntratumoral heterogeneity has an enormous effect on patient treatment and outcome. The purpose of the current study was to establish and validate a nomogram with intratumoral heterogeneity derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prognosis of 5-Year progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC).Methods A total of 171 NPC patients who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Data was randomly divided into training cohort (n=101) and validation cohort (n=70). The clinicopathologic parameters and the following PET parameters were analyzed: maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI, SUVmax/SUVmean) for primary tumor and maximal neck lymph node. Cox analyses were performed on PFS in the training cohort. A prognostic nomogram based on this model was developed and validated.ResultsFor the primary tumor, MTV-2.5, TLG-2.5, MTV-70%, and TLG-70% were significantly correlated with PFS. For the maximal neck lymph node, short diameter and HI were significantly correlated with PFS.Among the clinicopathologic parameters, M stage was a significant prognostic factor for recurrence. In multivariate analysis, M stage (P=0.006), TLG-T-70% (P=0.002), and HI-N (P=0.018) were independent predictors. Based on this prognostic model, a nomogram was generated. The C-index of this model was 0.74 (95% CI: 0.63-0.85). For the cross validation, the C-index for the model was 0.73 (95% CI: 0.62-0.83) with the validation cohort. Patients with a risk score of ≥111 had poorer survival outcomes than those with a risk score of 0-76 and 77-110.Conclusions Intratumoral heterogeneity derived from 18F-FDG PET/CT could predict long-term outcome in patients with primary NPC. A combination of PET parameters and the TNM stage enables better stratification of patients into subgroups with different PFS rates. distribution, ethnic variation, and histopathological characteristics[1]. There are approximately 129,000 newly diagnosed nasopharyngeal carcinoma and 73,000 patients die of this neoplasm worldwide in 2018[2]. According to the WHO criteria, keratinizing squamous cell carcinoma is defined as type I, whereas types II and III refer to non-keratinizing differentiated and undifferentiated carcinomas, respectively. In regions where nasopharyngeal carcinoma is endemic, e.g. South-Eastern Asia and North Africa, non-keratinizing carcinomas comprise almost 95% of cases, which are invariably associated with Epstein-Barr virus (EBV) infection[3]. Due to the anatomic location and high radiosensitivity, radiotherapy (RT) is the primary and only curative treatment for nasopharyngeal carcinoma. Meanwhile chemotherapy and targeted therapy also serve as pivotal advancement in the treatment of the locally advanced nasopharyngeal carcinoma[4-6]. However, the long-term prognosis remains relatively poor as the current therapeutic regimen...

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Prognostic significance of the intratumoral heterogeneity of ¹⁸F‐FDG uptake in oral cavity cancer

Abstract: The intratumoral heterogeneity of (18) F-FDG uptake may be a significant prognostic factor for overall survival in addition to cervical lymph node metastasis in oral cavity cancer. J. Surg. Oncol. 2014 110:702-706. © 2014 Wiley Periodicals, Inc.

Cited by 40 publications

References 27 publications

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics

Establishment and Validation of a Nomogram with Intratumoral Heterogeneity Derived from 18F-FDG PET/CT for Predicting Individual Conditional Risk of 5-Year Recurrence before Initial Treatment of Nasopharyngeal Carcinoma

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Prognostic significance of the intratumoral heterogeneity of 18F‐FDG uptake in oral cavity cancer

Abstract: The intratumoral heterogeneity of (18) F-FDG uptake may be a significant prognostic factor for overall survival in addition to cervical lymph node metastasis in oral cavity cancer. J. Surg. Oncol. 2014 110:702-706. © 2014 Wiley Periodicals, Inc.

Cited by 40 publications

References 27 publications

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters to Predict Prognosis in Patients With HPV-Positive Primary Oropharyngeal Squamous Cell Carcinoma

Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics

Establishment and Validation of a Nomogram with Intratumoral Heterogeneity Derived from 18F-FDG PET/CT for Predicting Individual Conditional Risk of 5-Year Recurrence before Initial Treatment of Nasopharyngeal Carcinoma

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Prognostic significance of the intratumoral heterogeneity of ¹⁸F‐FDG uptake in oral cavity cancer