Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer.

PURPOSE To investigate the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided intensity-modulated radiotherapy (IMRT) in dose escalation to attack the hypoxic volume of a tumor mass without increasing the normal tissue dose in head and neck cancer patients. MATERIALS AND METHODS Eight consecutive head and neck cancer patients underwent (18)F-FMISO PET/CT simulation. Hypoxic tumor volume (HTV) was defined using a tumor-to-cerebellum ratio (T/C) of 1.3 as the threshold for (18)F-FMISO PET/CT. Dose-escalation plans for treating HTVs using (18)F-FMISO PET/CT-guided IMRT were performed for these patients. The standard plan was 72Gy to the gross tumor volume (GTV) administered as 30 daily fractions of 2.4Gy. In biologically optimized IMRT plans, the daily dose to the HTV ranged from 2.6 to 3.6Gy. Dose-volume histograms (DVHs) were generated as part of each plan, and the results of planning were analyzed. RESULTS Dose-escalation IMRT plans, delivering 30 daily doses of 2.6Gy (total of 78Gy) to the HTVs without increases in normal tissue doses, were feasible for six patients. Further acceptable dose escalation on HTV depended primarily on the primary tumor site and the extent of disease. CONCLUSIONS It was possible to dose escalate the HTV radiation to 78Gy in six of eight head and neck cancer patients using (18)F-FMISO PET/CT-guided IMRT.

[1]  P Vaupel,et al.  Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  Daniel A Low,et al.  Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer. , 2003, International journal of radiation oncology, biology, physics.

[3]  Chapman Jd,et al.  Hypoxic sensitizers--implications for radiation therapy. , 1979 .

[4]  Nathan Lawrentschuk,et al.  Assessing regional hypoxia in human renal tumours using 18F‐fluoromisonidazole positron emission tomography , 2005, BJU international.

[5]  M. Eble,et al.  pO2 Polarography Versus Positron Emission Tomography ([18F] Fluoromisonidazole, [18F]-2-Fluoro-2’-Deoxyglucose) , 2004, Strahlentherapie und Onkologie.

[6]  J. Overgaard,et al.  A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  Daniela Thorwarth,et al.  Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[8]  M. Dewhirst,et al.  Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. , 1996, Cancer research.

[9]  Sadek Nehmeh,et al.  Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. , 2008, International journal of radiation oncology, biology, physics.

[10]  R Mohan,et al.  Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers. , 2000, International journal of radiation oncology, biology, physics.

[11]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[12]  M. Piert,et al.  Introducing fluorine-18 fluoromisonidazole positron emission tomography for the localisation and quantification of pig liver hypoxia , 1999, European Journal of Nuclear Medicine.

[13]  K. Krohn,et al.  Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. , 1989, International journal of radiation oncology, biology, physics.

[14]  Martin Westhofen,et al.  FDG—a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  David L. Schwartz,et al.  Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer , 2006, Clinical Cancer Research.

[16]  D. Mankoff,et al.  Hypoxia imaging-directed radiation treatment planning , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[17]  Sang‐wook Lee,et al.  Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma. , 2006, International journal of radiation oncology, biology, physics.

[18]  X Allen Li,et al.  Simultaneous integrated boost for breast cancer using IMRT: a radiobiological and treatment planning study. , 2004, International journal of radiation oncology, biology, physics.

[19]  Radhe Mohan,et al.  Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II--clinical results. , 2004, International journal of radiation oncology, biology, physics.

[20]  M. Dewhirst,et al.  Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. , 1997, International journal of radiation oncology, biology, physics.

[21]  T. Pickles,et al.  Impact of nicotinamide on human tumour hypoxic fraction measured using the comet assay. , 1997, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  M. Piert,et al.  Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver. , 2000, Nuclear medicine and biology.

[23]  S Mutic,et al.  A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy. , 2001, International journal of radiation oncology, biology, physics.

[24]  J. Deasy,et al.  A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. , 2001, International journal of radiation oncology, biology, physics.

[25]  Jens Overgaard,et al.  Tumor hypoxia is independent of hemoglobin and prognostic for loco-regional tumor control after primary radiotherapy in advanced head and neck cancer , 2004, Acta oncologica.

[26]  Matthias Reimold,et al.  Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  M. Graham,et al.  Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  P. Olive,et al.  Heterogeneity in human tumour hypoxic fraction using the comet assay. , 1996, The British journal of cancer. Supplement.

[29]  D. Brizel,et al.  Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[30]  Lester J. Peters,et al.  Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  R. Fisher,et al.  Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  I. Olivotto,et al.  Gel electrophoresis of individual cells to quantify hypoxic fraction in human breast cancers. , 1993, Cancer research.

[33]  P. Xia,et al.  Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. , 2001, International journal of radiation oncology, biology, physics.

[34]  Heinz H. Coenen,et al.  pO(2) Polarography versus positron emission tomography ([(18)F] fluoromisonidazole, [(18)F]-2-fluoro-2'-deoxyglucose). An appraisal of radiotherapeutically relevant hypoxia. , 2004 .

[35]  Richard A Popple,et al.  Tumor control probability for selective boosting of hypoxic subvolumes, including the effect of reoxygenation. , 2002, International journal of radiation oncology, biology, physics.