The utility of multiparametric MRI to characterize hypoxic tumor subvolumes in comparison to FMISO PET/CT. Consequences for diagnosis and chemoradiation treatment planning in head and neck cancer

Wiedenmann, Nicole; Grosu, Anca‐Ligia; Büchert, Martin; Rischke, Hans Christian; Ruf, Juri; Bielak, Lars; Majerus, L.; Rühle, Alexander; Bamberg, Fabian; Baltas, Dimos; Hennig, Jürgen; Mix, Michael; Bock, Michael; Nicolay, Nils H.

doi:10.1016/j.radonc.2020.06.013

Cited by 29 publications

(32 citation statements)

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“…This is in congruence with previous studies by Hompland et al who found negative correlations of ADC values and the hypoxic fraction in melanoma xenografts [31] and human prostate cancer [32,50]. A significant association of low ADC values and hypoxia, as detected by FMISO-PET, was also reported for head and neck cancers in a recent study by Wiedenmann et al [51] although a previous study described no significant correlation between the ADC and HIF-1α in oropharyngeal carcinoma [52].…”

Section: Discussionsupporting

confidence: 91%

“…FMISO-PET is sometimes seen as the gold standard to image tumor hypoxia and in theory directly depicts tumor oxygenation, whereas the ADC value from DW-MRI should be regarded as an indirect measure for hypoxia which quantitates tissue properties responsible for hypoxia such as cell density and stroma content [24,51]. However, DW-MRI has several potential advantages over FMISO-PET, including its wide availability, ease of use, no requirement for an intravenous contrast agent or tracer, and the absence of ionizing radiation [27].…”

Section: Discussionmentioning

confidence: 99%

“…However, DW-MRI has several potential advantages over FMISO-PET, including its wide availability, ease of use, no requirement for an intravenous contrast agent or tracer, and the absence of ionizing radiation [27]. On the other hand, limited availability, as well as the required logistics and tracer availability, can make hypoxia PET imaging demanding [24,51]. FMISO, the most widely used radiotracer for imaging hypoxia, exhibits comparatively slow pharmacokinetics and should be evaluated 2 to 4 hours after its administration [53], while the acquisition time of multi b-value DWI of the upper abdomen is usually a few minutes only [54].…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia-induced chemoresistance may be mediated by several factors, including the induction of various genes controlling cell metabolism and survival [3] as well as induction of stemness [60]. Therefore, information about tumor hypoxia may help to individualize therapy concepts, e.g., by dose escalation of radiation therapy in hypoxic tumors [51] as recently reported for non-small cell lung cancer [61]. Longitudinally monitoring tumor hypoxia during the course of treatment could be beneficial as tumor hypoxia may decrease during radiochemotherapy [51,62] which could make a readjustment of treatment necessary.…”

Section: Discussionmentioning

confidence: 99%

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Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Mayer

Kraft

Witzel

et al. 2020

Cancers

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Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Mayer

Kraft

Witzel

et al. 2020

Cancers

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“…Tumor-associated hypoxia is known to be a crucial factor regarding treatment outcomes of HNSCC patients undergoing chemoradiation, as hypoxia increases resistance to ionizing radiation 3 - 5 . Various approaches to monitor tumor hypoxia during chemoradiation have been studied, including histological analyses, pO2 polarography and different imaging modalities 6 - 11 . Fluorine-18 misonidazole positron emission tomography ([ 18 F]FMISO PET) has proven to be a reliable imaging method for non-invasive monitoring of tumor hypoxia 12 - 15 .…”

Section: Introductionmentioning

confidence: 99%

Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with Head-and-neck Squamous Cell Carcinoma undergoing Chemoradiation

et al. 2020

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Tumor-associated hypoxia influences the radiation response of head-and-neck cancer (HNSCC) patients, and a lack of early hypoxia resolution during treatment considerably deteriorates outcomes. As the detrimental effects of hypoxia are partly related to the induction of an immunosuppressive microenvironment, we investigated the interaction between tumor hypoxia dynamics and the PD-1/PD-L1 axis in HNSCC patients undergoing chemoradiation and its relevance for patient outcomes in a prospective trial. Methods: 49 patients treated with definitive chemoradiation for locally advanced HNSCC were enrolled in this trial and received longitudinal hypoxia PET imaging using fluorine-18 misonidazole ([ 18 F]FMISO) at weeks 0, 2 and 5 during treatment. Pre-therapeutic tumor biopsies were immunohistochemically analyzed regarding the PD-1/PD-L1 expression both on immune cells and on tumor cells, and potential correlations between the PD-1/PD-L1 axis and tumor hypoxia dynamics during chemoradiation were assessed using Spearman's rank correlations. Hypoxia dynamics during treatment were quantified by subtracting the standardized uptake value (SUV) index at baseline from the SUV values at weeks 2 or 5, whereby SUV index was defined as ratio of maximum tumor [ 18 F]FMISO SUV to mean SUV in the contralateral sternocleidomastoid muscle ( i.e. tumor-to-muscle ratio). The impact of the PD-1/PD-L1 expression alone and in combination with persistent tumor hypoxia on locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) was examined using log-rank tests and Cox proportional hazards models. Results: Neither PD-L1 nor PD-1 expression levels on tumor-infiltrating immune cells influenced LRC (HR = 0.734; p = 0.480 for PD-L1, HR = 0.991; p = 0.989 for PD-1), PFS (HR = 0.813; p = 0.597 for PD-L1, HR = 0.796; p = 0.713 for PD-1) or OS (HR = 0.698; p = 0.405 for PD-L1, HR = 0.315; p = 0.265 for PD-1). However, patients with no hypoxia resolution between weeks 0 and 2 and PD-L1 expression on tumor cells, quantified by a tumor proportional score (TPS) of at least 1%, showed significantly worse LRC (HR = 3.374, p = 0.022) and a trend towards reduced PFS (HR = 2.752, p = 0.052). In the multivariate Cox regression analysis, the combination of absent tumor hypoxia resolution and high tumoral PD-L1 expression remained a significant prognosticator for impaired LRC (HR = 3.374, p = 0.022). On the other side, tumoral PD-L1 expression did not compromise the outcomes of patients whose tumor-associated hypoxia declined between week 0 and 2 during chemoradiation (LRC: HR = 1.186, p = 0.772, PFS: HR = 0.846, p = 0.766). Conclusion: In this...

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Correlations between DW‐MRI and ¹⁸F‐FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo‐radiotherapy

et al. 2021

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Background: Posttreatment diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxygluocose ( 18 F-FDG) positron emission tomography (PET) with computed tomography (PET/CT) have potential prognostic value following chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Correlations between these PET/CT (standardized uptake value or SUV) and DW-MRI (apparent diffusion coefficient or ADC) parameters have only been previously explored in the pretreatment setting.Aim: To evaluate stage III and IV HNSCC at 12-weeks post-CRT for the correlation between SUV max and ADC values and their interval changes from pretreatment imaging.Methods: Fifty-six patients (45 male, 11 female, mean age 59.9 + − 7.38) with stage 3 and 4 HNSCC patients underwent 12-week posttreatment DW-MRI and 18 F-FDG PET/CT studies in this prospective study. There were 41/56 patients in the cohort with human papilloma virus-related oropharyngeal cancer (HPV OPC). DW-MRI (ADC max and ADC min) and 18 F-FDG PET/CT (SUV max and SUV max ratio to liver) parameters were measured at the site of primary tumors (n = 48) and the largest lymph nodes (n = 52). Kendall's tau evaluated the correlation between DW-MRI and 18 F-FDG PET/CT parameters. Mann-Whitney test compared the post-CRT PET/CT and DW-MRI parameters between those participants with and without 2-year disease-free survival (DFS).Results: There was no correlation between DW-MRI and 18 F-FDG PET/CT parameters on 12-week posttreatment imaging (P = .455-.794; tau = −0.075-0.25) or their interval changes from pretreatment to 12-week posttreatment imaging (P = .1-.946; tau = −0.194-0.044). The primary tumor ADC mean (P = .03) and the interval change in nodal ADC min (P = .05) predicted 2-year DFS but none of the 18 F-FDG PET/CT parameters were associated with 2-year DFS.

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The utility of multiparametric MRI to characterize hypoxic tumor subvolumes in comparison to FMISO PET/CT. Consequences for diagnosis and chemoradiation treatment planning in head and neck cancer

Cited by 29 publications

References 36 publications

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with Head-and-neck Squamous Cell Carcinoma undergoing Chemoradiation

Correlations between DW‐MRI and ¹⁸F‐FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo‐radiotherapy

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The utility of multiparametric MRI to characterize hypoxic tumor subvolumes in comparison to FMISO PET/CT. Consequences for diagnosis and chemoradiation treatment planning in head and neck cancer

Cited by 29 publications

References 36 publications

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Hypoxia dynamics on FMISO-PET in combination with PD-1/PD-L1 expression has an impact on the clinical outcome of patients with Head-and-neck Squamous Cell Carcinoma undergoing Chemoradiation

Correlations between DW‐MRI and 18F‐FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo‐radiotherapy

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Correlations between DW‐MRI and ¹⁸F‐FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo‐radiotherapy