Hypoxia in cervical cancer: from biology to imaging

Lyng, Heidi; Malinen, Eirik

doi:10.1007/s40336-017-0238-7

Cited by 43 publications

(36 citation statements)

References 121 publications

(143 reference statements)

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“…In addition to MRI, positron emission tomography (PET)/computed tomography (CT) has shown promise for hypoxia imaging. Current studies are investigating the potential of several PET hypoxia tracers, including 18 F-fluoromisonidazole, 18 F-fluoroerythronitroimidazole, 18 F-fluoroazomycinarabinoside, and 60 Cu-diacetyl-bis(N-methylthiosemicarbazone), and interesting observations have been reported [24]. It has also been hypothesized that 18 Ffluorodeoxyglucose ( 18 F-FDG) may be a clinically useful surrogate hypoxia tracer [24].…”

Section: Discussionmentioning

confidence: 99%

“…Current studies are investigating the potential of several PET hypoxia tracers, including 18 F-fluoromisonidazole, 18 F-fluoroerythronitroimidazole, 18 F-fluoroazomycinarabinoside, and 60 Cu-diacetyl-bis(N-methylthiosemicarbazone), and interesting observations have been reported [24]. It has also been hypothesized that 18 Ffluorodeoxyglucose ( 18 F-FDG) may be a clinically useful surrogate hypoxia tracer [24]. If this hypothesis proves to be valid, 18 F-FDG PET/CT may turn out be a powerful imaging modality for LACC, since 18 F-FDG PET/CT already is used successfully to detect pathological lymph nodes and high-risk radiation therapy targets [25,26].…”

Section: Discussionmentioning

confidence: 99%

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DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

et al. 2020

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Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide biomarkers of the outcome of locally-advanced cervical carcinoma (LACC). There is, however, no agreement on how DCE-MR recordings should be analyzed. Previously, we have analyzed DCE-MRI data of LACC using non-model-based strategies. In the current study, we analyzed DCE-MRI data of LACC using the Tofts pharmacokinetic model, and the biomarkers derived from this analysis were compared with those derived from the non-model-based analyses. Methods: Eighty LACC patients given cisplatin-based chemoradiotherapy with curative intent were included in the study. Treatment outcome was recorded as disease-free survival (DFS) and overall survival (OS). DCE-MRI series were analyzed voxelwise to produce K trans and v e frequency distributions, and ROC analysis was used to identify the parameters of the frequency distributions having the greatest potential as biomarkers. The prognostic power of these parameters was compared with that of the non-model-based parameters LETV (low-enhancing tumor volume) and TVIS (tumor volume with increasing signal). Results: Poor DFS and OS were associated with low values of K trans , whereas there was no association between treatment outcome and v e . The K trans parameters having the greatest prognostic value were p35-K trans (the K trans value at the 35 percentile of a frequency distribution) and RV-K trans (the tumor subvolume with K trans values below 0.13 min − 1 ). Multivariate analysis including clinical parameters and p35-K trans or RV-K trans revealed that RV-K trans was the only independent prognostic factor of DFS and OS. There were significant correlations between RV-K trans and LETV and between RV-K trans and TVIS, and the prognostic power of RV-K trans was similar to that of LETV and TVIS. Conclusions: Biomarkers of the outcome of LACC can be provided by analyzing DCE-MRI series using the Tofts pharmacokinetic model. However, these biomarkers do not appear to have greater prognostic value than biomarkers determined by non-model-based analyses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

et al. 2020

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“…However, the spatial resolution associated with PET imaging is low compared to the size of the hypoxic regions that can be found in tumor tissue [5]. Magnetic resonance imaging (MRI) techniques, including blood oxygen level dependent MRI (BOLD-MRI), tissue oxygen level dependent MRI (TOLD-MRI), oxygen-enhanced MRI (OE-MRI), and dynamic contrast-enhanced MRI (DCE-MRI), have also been applied to study tumor hypoxia [4,5,7,8]. MRI can be performed with substantially higher spatial resolution than PET imaging, and DCE-MRI is highly attractive because the technique is associated with a high signal to noise ratio and is routinely used to detect and characterize various types of cancer in the clinic.…”

Section: Introductionmentioning

confidence: 99%

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Gaustad

Hauge

Wegner

et al. 2020

Cancers

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Tumor hypoxia is associated with resistance to treatment, aggressive growth, metastatic dissemination, and poor clinical outcome in many cancer types. The potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the extent of hypoxia in tumors has been investigated in several studies in our laboratory. Cervical carcinoma, melanoma, and pancreatic ductal adenocarcinoma (PDAC) xenografts have been used as models of human cancer, and the transfer rate constant (Ktrans) and the extravascular extracellular volume fraction (ve) have been derived from DCE-MRI data by using Tofts standard pharmacokinetic model and a population-based arterial input function. Ktrans was found to reflect naturally occurring and treatment-induced hypoxia when hypoxia was caused by low blood perfusion, radiation responsiveness when radiation resistance was due to hypoxia, and metastatic potential when metastasis was hypoxia-induced. Ktrans was also associated with outcome for patients with locally-advanced cervical carcinoma treated with cisplatin-based chemoradiotherapy. Together, the studies imply that DCE-MRI can provide valuable information on the hypoxic status of cervical carcinoma, melanoma, and PDAC. In this communication, we review and discuss the studies and provide some recommendations as to how DCE-MRI data can be analyzed and interpreted to assess tumor hypoxia.

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“…The classical ICBT delivers excellent local control rates for amenable tumors by taking advantage of this property (3).…”

Section: Introductionmentioning

confidence: 99%

Long-term effectiveness and safety of image-based, transperineal combined intracavitary and interstitial brachytherapy in treatment of locally advanced cervical cancer

Tiwari

Narayanan

et al. 2020

Brachytherapy

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The aim of the study was to evaluate the impact of image-based combined intracavitary-interstitial brachytherapy (IC-ISBT) using a transperineal template in locally advanced cervical cancer treatment. METHODS AND MATERIALS: A total of 94 patients of cervical cancer stage IIB-IVA underwent image-based transperineal interstitial brachytherapy without tandem (ISBT) or with tandem (IC-ISBT) between June 2008 and June 2018 at our institution. After pelvic chemoradiation, 42 patients underwent ISBT and 52 IC-ISBT. Dosimetric data, clinical response, and toxicity records of these patients were reviewed. RESULTS: Clinical stage distribution was as follows: IIB: 22.4% (21), IIIA: 10.6% (10), IIIB: 56.4% (53), and IVA: 10.6% (10). Mean high-risk clinical target volume was 75.72 cc, and mean cumulative equivalent of 2 Gy per fraction for high-risk clinical target volume was 81 Gy. The median followup was 35.5 months. Overall 3-and 5-year local control, disease-free survival (DFS), and overall survival (OS) were 84% and 84%, 69.1% and 62.9%, and 80.9% and 71.5%, respectively. Local control (90.4% vs. 76.2%; p 5 0.048) and DFS (78.8% vs. 57.1%; p 5 0.04) were significantly better in the patients of IC-ISBT arm. IC-ISBT (hazard ratio: 0.763; 95% confidence interval 0.217, 1.38; p 5 0.046) and D90 dose O85 Gy (hazard ratio: 0.957; 95% confidence interval 0.927, 1.07; p 5 0.037) were predictors of better DFS on univariate analysis. Overall survival was not affected significantly by any of the factors. Grade 3 and 4 late complications were recorded in 3.2% (3) of patients and were similar in both arms (p 5 0.86). However, the mean rectum 2 cc dose was significantly lower in the IC-ISBT arm (p 5 0.038). CONCLUSIONS: Combined IC-ISBT is a safe and effective approach to treat ICBT unsuitable cases. It integrates the benefits of ICBT to the adaptability of ISBT around various targets and should be practiced whenever feasible to provide superior outcomes in locally advanced cervical cancer.

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Hypoxia in cervical cancer: from biology to imaging

Cited by 43 publications

References 121 publications

DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

DCE-MRI of locally-advanced carcinoma of the uterine cervix: Tofts analysis versus non-model-based analyses

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Long-term effectiveness and safety of image-based, transperineal combined intracavitary and interstitial brachytherapy in treatment of locally advanced cervical cancer

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