Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma

Schuurbiers, Olga C.J.; Meijer, T.; Kaanders, J.H.A.M.; Looijen-Salamon, Monika; Geus-Oei, Lioe-Fee de; Drift, Miep A. van der; Heijden, Erik H F M van der; Oyen, Wim J.G.; Visser, Eric P.; Span, Paul N.; Bussink, Johan

doi:10.1097/jto.0000000000000286

Cited by 118 publications

(121 citation statements)

References 41 publications

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“…These results are consistent with those of a recent study (34) in which authors showed that, although lung squamous cell carcinomas tend to be more metabolically active with a higher SUV at FDG PET (generally a poor prognostic indicator), adenocarcinoma actually may have a higher metastatic potential than squamous cell carcinoma. On the other hand, the optimal imaging predictors of distant metastasis may be histologically specific.…”

Section: Thoracic Imaging: Predicting Distant Metastasis In Lung Cancsupporting

confidence: 82%

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

Wu¹,

Aguilera²,

Shultz³

et al. 2016

Radiology

158

123

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Purpose:To identify quantitative imaging biomarkers at fluorine 18 ( 18 F) positron emission tomography (PET) for predicting distant metastasis in patients with early-stage non-small cell lung cancer (NSCLC). Materials andMethods:In this institutional review board-approved HIPAA-compliant retrospective study, the pretreatment 18 F fluorodeoxyglucose PET images in 101 patients treated with stereotactic ablative radiation therapy from 2005 to 2013 were analyzed. Data for 70 patients who were treated before 2011 were used for discovery purposes, while data from the remaining 31 patients were used for independent validation. Quantitative PET imaging characteristics including statistical, histogram-related, morphologic, and texture features were analyzed, from which 35 nonredundant and robust features were further evaluated. Cox proportional hazards regression model coupled with the least absolute shrinkage and selection operator was used to predict distant metastasis. Whether histologic type provided complementary value to imaging by combining both in a single prognostic model was also assessed. Results:The optimal prognostic model included two image features that allowed quantification of intratumor heterogeneity and peak standardized uptake value. In the independent validation cohort, this model showed a concordance index of 0.71, which was higher than those of the maximum standardized uptake value and tumor volume, with concordance indexes of 0.67 and 0.64, respectively. The prognostic model also allowed separation of groups with low and high risk for developing distant metastasis (hazard ratio, 4.8; P = .0498, log-rank test), which compared favorably with maximum standardized uptake value and tumor volume (hazard ratio, 1.5 and 2.0, respectively; P = .73 and 0.54, log-rank test, respectively). When combined with histologic types, the prognostic power was further improved (hazard ratio, 6.9; P = .0289, log-rank test; and concordance index, 0.80). Conclusion:PET imaging characteristics associated with distant metastasis that could potentially help practitioners to tailor appropriate therapy for individual patients with earlystage NSCLC were identified.q RSNA, 2016

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Section: Thoracic Imaging: Predicting Distant Metastasis In Lung Cancsupporting

confidence: 82%

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

Wu¹,

Aguilera²,

Shultz³

et al. 2016

Radiology

158

123

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“…The described changes say about more severe hypoxia features in squamous cell lung carcinoma. [43,44] The identified changes in the activity of metabolic enzymes in lung cancer of various histological types show that hypoxia is a factor that conditions the metabolic shift. However, hypoxic features should be implicitly unevenly manifested for peripheral and central lung cancers.…”

Section: Discussionmentioning

confidence: 99%

The activity of metabolic enzymes in the saliva of lung cancer patients

Bel’skaya¹,

Kosenok²

2017

Natl J Physiol Pharm Pharmacol

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Background: So far, optimization problems for diagnostics and prognostication aids have been still relevant for lung cancer as a leader in the structure of cancers. Aims and Objectives: A search for regularities of changes in the saliva enzyme activity in patients with lung cancer. Materials and Methods: In the case-control study, 859 people divided into two groups took part: Primary (lung cancer, n = 286) and control (conventionally healthy, n = 573). All the participants went through a questionnaire survey, saliva biochemical counts, and a histological verification of their diagnosis. The enzyme activity was measured by spectrophotometry. Between group differences were measured with the nonparametric test. Results: In terms of lung cancer, we observe metabolic changes described with decreased de Ritis coefficient (P ˂ 0.001), as well as the increased activity of alanine aminotransferase (P = 0.022), alkaline phosphatase (P ˂ 0.001), gamma-glutamyl transpeptidase (P = 0.043), and α-amylase (P ˂ 0.001). We have identified specifics of the change in the enzyme activity depending on a histological type and a growth form of the tumor. There is the observable increased activity of α-amylase in the saliva in lung adenocarcinoma and neuroendocrine tumors (P ˂ 0.001). It has been found that irrespective of the histological type of lung cancer in a transition from central to peripheral forms of growth; there is the observable increased activity of all the enzymes. The significantly reduced activity of aspartate aminotransferase (by 51.4% for adenocarcinoma, P = 0.032; 48.8% for squamous cell lung cancer, P = 0.042) is a distinctive feature of central lung cancer. Conclusion: The nature of the change in the enzyme activity is ambiguous and to a greater degree depends on the tumor form of growth (central/peripheral lung cancer) than the histological type (adenocarcinoma/squamous cell lung cancer).

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“…Around 20–40% of patients with NSCLC develop BMs, and the adenocarcinoma subtype is generally more invasive than the squamous cell carcinoma subtype (50). Despite its less metastatic nature, squamous cell carcinoma exhibits an elevated glucose metabolism due to impaired blood vessel growth and tumor hypoxia (51). Therefore, it is important to evaluate metabolic state concurrently with other phenotypic and prognostic markers when assessing metastatic potential.…”

Section: Lung-to-brain Metastasesmentioning

confidence: 99%

Metabolic advantages and vulnerabilities in brain metastases

Ciminera

Jandial

Termini

2017

Clin Exp Metastasis

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Metabolic adaptations permit tumor cells to metastasize to and thrive in the brain. Brain metastases continue to present clinical challenges due to rising incidence and resistance to current treatments. Therefore, elucidating altered metabolic pathways in brain metastases may provide new therapeutic targets for the treatment of aggressive disease. Due to the high demand for glucose in the brain, increased glycolytic activity is favored for energy production. Primary tumors that undergo Warburg-like metabolic reprogramming become suited to growth in the brain microenvironment. Indeed, elevated metabolism is a predictor of metastasis in many cancer subtypes. Specifically, metabolic alterations are seen in primary tumors that are associated with the formation of brain metastases, namely breast cancer, lung cancer, and melanoma. Because of this selective pressure, inhibitors of key metabolic factors may reduce tumor cell viability, thus exploiting metabolic pathways for cancer therapeutics. This review summarizes the metabolic advantages and vulnerabilities of brain metastases.

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Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma

Cited by 118 publications

References 41 publications

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

The activity of metabolic enzymes in the saliva of lung cancer patients

Metabolic advantages and vulnerabilities in brain metastases

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Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma

Cited by 118 publications

References 41 publications

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of18F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of18F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

The activity of metabolic enzymes in the saliva of lung cancer patients

Metabolic advantages and vulnerabilities in brain metastases

Contact Info

Product

Resources

About

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis

Early-Stage Non–Small Cell Lung Cancer: Quantitative Imaging Characteristics of¹⁸F Fluorodeoxyglucose PET/CT Allow Prediction of Distant Metastasis