Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study

Nordsmark, Marianne; Bentzen, Søren M.; Rudat, Volker; Brizel, David M.; Lartigau, Éric; Stadler, Peter F.; Becker, Axel; Adam, Markus; Molls, M.; Dunst, Juergen; Terris, David J.; Overgaard, Jens

doi:10.1016/j.radonc.2005.06.038

Cited by 857 publications

(559 citation statements)

References 28 publications

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“…Tumor hypoxia has been shown to be one of the major factors affecting treatment resistance in HNSCC (31). Noninvasive 18 F-fluoromisonidazole PET evaluating the gross disease can provide serial quantitative measurements of hypoxia, with potential prognostic implications (9,10).…”

Section: Discussionmentioning

confidence: 99%

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Dirix¹,

Vandecaveye²,

Keyzer³

et al. 2009

J Nucl Med

191

109

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The purpose of this work was to evaluate the potential of functional imaging with 18 F-FDG PET, 18 F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI to provide an appropriate and reliable biologic target for dose painting in radiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods: Fifteen patients with locally advanced HNSCC, treated with concomitant chemoradiotherapy, were prospectively enrolled in a bioimaging protocol. Sequential PET ( 18 F-FDG and 18 F-fluoromisonidazole) and MRI (T1, T2, dynamic enhanced, and diffusion-weighted sequences) were performed before, during, and after radiotherapy. Results: Median follow-up was 30.7 mo (range, 6.3-56.3 mo); in 7 patients, disease recurred. Disease-free survival correlated negatively with the maximum tissue-to-blood 18 F-fluoromisonidazole ratio (T/B max ) on the baseline 18 F-fluoromisonidazole scan (P 5 0.04), with the size of the initial hypoxic volume (P 5 0.04), and with T/B max on the 18 F-fluoromisonidazole scan during treatment (P 5 0.02). All locoregional recurrences were within the 18 F-FDGavid regions on baseline 18 F-FDG PET; 3 recurrences mapped outside the hypoxic volume on baseline 18 F-fluoromisonidazole PET. Lesions (primary tumor and lymph nodes) where a locoregional recurrence developed during follow-up had significantly lower apparent diffusion coefficients on diffusion-weighted MRI during week 4 of radiotherapy (0.0013 vs. 0.0018 mm 2 /s, P 5 0.01) and at 3 wk after treatment (0.0014 vs. 0.0018 mm 2 /s, P 5 0.01) and a significantly higher initial slope on baseline dynamic enhanced MRI (26.2 vs. 17.5/s, P 5 0.03) than did lesions that remained controlled. Conclusion: These results confirm the added value of 18 F-FDG PET and 18 F-fluoromisonidazole PET for radiotherapy planning of HNSCC and suggest the potential of diffusion-weighted and dynamic enhanced MRI for dose painting and early response assessment.

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Section: Discussionmentioning

confidence: 99%

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Dirix¹,

Vandecaveye²,

Keyzer³

et al. 2009

J Nucl Med

191

109

View full text Add to dashboard Cite

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“…Clinical investigations have shown that extensive hypoxia, elevated interstitial fluid pressure, and high lactate concentration in the primary tumor are associated with high incidence of regional and distant metastases and, hence, poor disease-free and overall survival rates in several histologic types of cancer (5)(6)(7)(8)(9)(10)(11)(12). However, these clinical observations do not necessarily implicate that a hostile tumor microenvironment promotes metastasis and poor survival rates.…”

Section: Introductionmentioning

confidence: 99%

Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice

et al. 2006

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Extracellular pH (pH e ) is lower in many tumors than in the corresponding normal tissue. The significance of acidic pH e in the development of metastatic disease was investigated in the present work. Human melanoma cells (A-07, D-12, and T-22) were cultured in vitro at pH e 6.8 or 7.4 (control) before being inoculated into the tail vein of BALB/c nu/nu mice for formation of experimental pulmonary metastases. Cell invasiveness was studied in vitro by using Matrigel invasion chambers and angiogenesis was studied in vivo by using an intradermal assay. Protein secretion was measured by ELISA and immunocapture assays. Cells cultured at acidic pH e showed increased secretion of proteinases and proangiogenic factors, enhanced invasive and angiogenic potential, and enhanced potential to develop experimental metastases. Acidity-induced metastasis was inhibited by treatment with the general matrix metalloproteinase (MMP) inhibitor GM6001, the general cysteine proteinase inhibitor E-64, or blocking antibody against vascular endothelial growth factor-A (VEGF-A) or interleukin-8 (IL-8). Our study indicates that acidic pH e promotes experimental pulmonary metastasis in A-07, D-12, and T-22 human melanoma cells by a common mechanism involving acidity-induced up-regulation of the proteolytic enzymes MMP-2, MMP-9, cathepsin B, and cathepsin L and acidity-induced up-regulation of the proangiogenic factors VEGF-A and IL-8. One consequence of this observation is that treatment strategies involving deliberate tumor acidification to improve the efficacy of chemotherapy, photodynamic therapy, and hyperthermia should be avoided. Moreover, the possibility that the pH e of the primary tumor may be an important prognostic parameter for melanoma patients merits clinical investigation. (Cancer Res 2006; 66(13): 6699-707)

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“…Hypoxia can render tumor cells up to three times more resistant to radiation relative to aerobic cells (7). Hypoxia has been shown in several studies to be an important determinant of locoregional control (LRC) and overall survival in many tumors, including head and neck cancer (HNC) (2,(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Lee

Mechalakos

Nehmeh

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

210

157

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Purpose-Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV h ) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV h increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ( 18 F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.Methods and Materials-18 F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and 18 F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated 18 F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate 18 F-FMISO PET/CT-guided IMRT plans.Results-The heterogeneous distribution of 18 F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing 18 F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV h and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV h for 2 patients and were successful in 1, with normal tissue sparing. Conclusion-It was feasible to dose escalate the GTV h to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

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Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study

Cited by 857 publications

References 28 publications

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

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Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study

Cited by 857 publications

References 28 publications

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with18F-FDG PET,18F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with18F-FDG PET,18F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Contact Info

Product

Resources

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Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with¹⁸F-FDG PET,¹⁸F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI