FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: Results from the DAHANCA 24 trial

Mortensen, Lise Saksø; Johansen, Jørgen; Kallehauge, J.; Primdahl, Hanne; Busk, Morten; Lassen, P.; Alsner, Jan; Sørensen, Brita Singers; Toustrup, Kasper; Jakobsen, Steen; Petersen, J.; Petersen, Henrik; Theil, Jørn; Nordsmark, Marianne; Overgaard, Jens

doi:10.1016/j.radonc.2012.09.015

Cited by 279 publications

(204 citation statements)

References 34 publications

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“…Reischl et al [165] , Piert et al [166] , Picchio et al [167] , Maier et al [168] , Tran et al [169] Barthel et al [187] Busk et al [170] , Mortensen et al [171] , Piert et al [166] , Tran et al [169] Barthel et al [187] Busk et al [170] , Busk et al [172] , Busk et al [173] , Busk et al [174] , Busk et al [175] , Graves et al [176] , Maier et al [168] , Solomon et al [177] NA Belloli et al [178] , Picchio et al [167] , Troost et al [179] , Valtorta et al [143] NA Sorger et al [57] , Piert et al [166] , Reischl et al [165] Rasey et al [188] Postema et al [180] , Bollineni et al [181] , Trinkaus et al [58] , Verwer et al [59] NA Grosu et al [182] , Souvatzoglou et al [183] , Schuetz et al [184] , Shi et al [106] , Mortensen et al [185] , Havelund et al [186] NA…”

Section: F]ef5mentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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Core tip:This review provides an overview of the current applications of positron emission tomography for hypoxia and perfusion imaging in lung cancer. Available PET tracers are discussed and the benefits of combined hypoxia and perfusion PET imaging are clarified. Hypoxia imaging could aid in selecting patients for hypoxia-specific treatment strategies. To achieve this, consensus about the optimal imaging protocol and quantification method is essential. Large clinical trials are needed to confirm the value of hypoxia imaging for improving patient care.Verwer EE, Boellaard R, van der Veldt AAM. Positron emission tomography to assess hypoxia and perfusion in lung cancer.

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Section: F]ef5mentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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“…In a multi-institutional study on 397 patients with locally advanced HNSCC, Nordsmark and colleagues found that pretreatment tumor oxygenation is a highly significant prognostic factor for survival after primary radiotherapy applied alone or combined with chemotherapy, surgery, or radiation sensitizers (12). In recent years, hypoxia detection using [(18F)]-fluoroazomycin arabinoside (FAZA) PET/CT and [(18F)]-fluoromisonidazole (FMISO) PET/CT imaging have been found to have a prognostic potential in HNSCC (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…The 26-gene classifier by Eustace and colleagues, that is based on this metagene signature (18), has been shown to predict the benefit from hypoxia-modifying treatment in laryngeal cancer (16). However, as the gene classifiers are based on the measurement of hypoxia-induced gene expression and not on hypoxia itself, the classification by the gene signature does not necessarily correlate with hypoxia assessed by PET (13,19).…”

Section: Introductionmentioning

confidence: 99%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

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143

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Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

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“…Molecular imaging may be able to identify spatial patterns of radioresistance, which can be used to guide and shape the dose distribution. Indirect evidence of this principle comes from studies that have found molecular imaging biomarkers to correlate with patient outcome after radiation therapy (60,61). Possible biologic targets include tumor hypoxia (measured with PET hypoxia radiotracers or with dynamic contrast-enhanced [DCE] MRI), cellularity (measured with 18 F-FDG PET or DW MRI), and others.…”

Section: Tumor Boostingmentioning

confidence: 99%

Molecular Imaging to Plan Radiotherapy and Evaluate Its Efficacy

2015

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) how to acquire high-quality molecular images for use in radiation therapy; (2) how molecular imaging can be used to plan radiotherapy and evaluate treatment efficacy; and (3) the limitations and challenges to widespread use of molecular imaging in radiation oncology.Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through November 2018.Molecular imaging plays a central role in the management of radiation oncology patients. Specific uses of imaging, particularly to plan radiotherapy and assess its efficacy, require an additional level of reproducibility and image quality beyond what is required for diagnostic imaging. Specific requirements include proper patient preparation, adequate technologist training, careful imaging protocol design, reliable scanner technology, reproducible software algorithms, and reliable data analysis methods. As uncertainty in target definition is arguably the greatest challenge facing radiation oncology, the greatest impact that molecular imaging can have may be in the reduction of interobserver variability in target volume delineation and in providing greater conformity between target volume boundaries and true tumor boundaries. Several automatic and semiautomatic contouring methods based on molecular imaging are available but still need sufficient validation to be widely adopted. Biologically conformal radiotherapy (dose painting) based on molecular imaging-assessed tumor heterogeneity is being investigated, but many challenges remain to fully exploring its potential. Molecular imaging also plays increasingly important roles in both early (during treatment) and late (after treatment) response assessment as both a predictive and a prognostic tool. Because of potentially confounding effects of radiation-induced inflammation, treatment response assessment requires careful interpretation. Although molecular imaging is already strongly embedded in radiotherapy, the path to widespread and all-inclusive use is still long. The lack of solid clinical evidence is the main impediment to broader use. Recommendations for practicing physicians are still rather scarce. 18 F-FDG PET/CT remains the main molecular imaging modality in radiation oncology applications. Although other molecular imaging options (e.g., proliferation imaging) are becoming more common, their widespread use is limited ...

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FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: Results from the DAHANCA 24 trial

Abstract: This study emphasizes the role of FAZA PET/CT imaging as a suitable assay with prognostic potential for detection of hypoxia in HNSCC.

Cited by 279 publications

References 34 publications

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Molecular Imaging to Plan Radiotherapy and Evaluate Its Efficacy

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