Improving target definition for head and neck radiotherapy: a place for magnetic resonance imaging and 18-fluoride fluorodeoxyglucose positron emission tomography?

Defining the target for head and neck radiotherapy is a critical issue with the introduction of steep dose gradients associated with intensity-modulated radiotherapy. Tumour delineation inaccuracies are a major source of error in radiotherapy planning. The integration of 18-fluoride fluorodeoxyglucose positron emission tomography ((18)FDG-PET) and magnetic resonance imaging directly into the radiotherapy planning process has the potential to greatly improve target identification/selection and delineation. This raises a range of new issues surrounding image co-registration, delineation methodology and the use of functional data and treatment adaptation. This overview will discuss the practical aspects of integrating (18)FDG-PET and magnetic resonance imaging into head and neck radiotherapy planning.

[1]  C. Njeh,et al.  Tumor delineation: The weakest link in the search for accuracy in radiotherapy , 2008, Journal of medical physics.

[2]  John P A Ioannidis,et al.  F-Fluorodeoxyglucose Positron Emission Tomography to Evaluate Cervical Node Metastases in Patients With Head and Neck Squamous Cell Carcinoma: A Meta-analysis , 2008 .

[3]  Jeong Hyun Lee,et al.  Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma. , 2007, Oral oncology.

[4]  J. Freeman,et al.  MRI and neck metastases: a clinical, radiological, pathological correlative study. , 1990, The Journal of otolaryngology.

[5]  Sotirios Bisdas,et al.  18F-Fluorodeoxyglucose-PET/CT to evaluate tumor, nodal disease, and gross tumor volume of oropharyngeal and oral cavity cancer: comparison with MR imaging and validation with surgical specimen , 2009, Neuroradiology.

[6]  T. Hibi,et al.  Limited Capability of Regional Lymph Nodes to Eradicate Metastatic Cancer Cells , 2004, Cancer Research.

[7]  Piotr J Slomka,et al.  Software Approach to Merging Molecular with Anatomic Information , 2004 .

[8]  S. Rafla,et al.  The impact of positron emission tomography/computed tomography in edge delineation of gross tumor volume for head and neck cancers. , 2007, International journal of radiation oncology, biology, physics.

[9]  G. Snow,et al.  The size of lymph nodes in the neck on sonograms as a radiologic criterion for metastasis: how reliable is it? , 1998, AJNR. American journal of neuroradiology.

[10]  B. Carey,et al.  Functional imaging for head and neck cancer. , 2010, The Lancet. Oncology.

[11]  Kevin Harrington,et al.  An exploratory study into the role of dynamic contrast-enhanced magnetic resonance imaging or perfusion computed tomography for detection of intratumoral hypoxia in head-and-neck cancer. , 2009, International journal of radiation oncology, biology, physics.

[12]  Xavier Geets,et al.  Adaptive biological image-guided IMRT with anatomic and functional imaging in pharyngo-laryngeal tumors: impact on target volume delineation and dose distribution using helical tomotherapy. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  Alicia Y Toledano,et al.  An evaluation of the variability of tumor-shape definition derived by experienced observers from CT images of supraglottic carcinomas (ACRIN protocol 6658). , 2007, International journal of radiation oncology, biology, physics.

[14]  J. Woolgar,et al.  Magnetic resonance imaging in the assessment of cervical nodal metastasis in oral squamous cell carcinoma. , 1999, Clinical radiology.

[15]  Paul Kinahan,et al.  Tumor delineation using PET in head and neck cancers: threshold contouring and lesion volumes. , 2006, Medical physics.

[16]  R. Hermans,et al.  Applications of diffusion-weighted magnetic resonance imaging in head and neck squamous cell carcinoma , 2010, Neuroradiology.

[17]  A. Garden,et al.  Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes. , 2006, International journal of radiation oncology, biology, physics.

[18]  P. Vaupel,et al.  Hypoxia in cancer: significance and impact on clinical outcome , 2007, Cancer and Metastasis Reviews.

[19]  J. Brunt.  Computed tomography-magnetic resonance image registration in radiotherapy treatment planning. , 2010, Clinical oncology (Royal College of Radiologists (Great Britain)).

[20]  C. Grau,et al.  Prospective study of 18FDG‐PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA‐13 study , 2008, Head & neck.

[21]  Shih-Neng Yang,et al.  18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters , 2010, Radiation oncology.

[22]  Aswin L Hoffmann,et al.  Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer. , 2007, International journal of radiation oncology, biology, physics.

[23]  W. De Neve,et al.  Intensity-modulated radiotherapy for sinonasal tumors: Ghent University Hospital update. , 2009, International journal of radiation oncology, biology, physics.

[24]  J. Thariat,et al.  Imaging work up of small aggressive lymph nodes: in regard to Ghadjar et al. (Int J Radiat Oncol Biol Phys 2010;78:1366-1372). , 2011, International journal of radiation oncology, biology, physics.

[25]  F. De Keyzer,et al.  Diffusion-weighted MRI for nodal staging of head and neck squamous cell carcinoma: impact on radiotherapy planning. , 2010, International journal of radiation oncology, biology, physics.

[26]  A. Scarsbrook,et al.  False-positive uptake on 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in oncological imaging. , 2011, Clinical radiology.

[27]  Brian O'Sullivan,et al.  Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Vincent Grégoire,et al.  Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  D. Yeung,et al.  Malignant cervical lymphadenopathy: diagnostic accuracy of diffusion-weighted MR imaging. , 2007, Radiology.

[30]  B. Seifert,et al.  PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison , 2007, Radiation oncology.

[31]  J. Lee,et al.  Segmentation of positron emission tomography images: some recommendations for target delineation in radiation oncology. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[32]  Benoît Macq,et al.  Comparison of 12 deformable registration strategies in adaptive radiation therapy for the treatment of head and neck tumors. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  B J McNeil,et al.  Comparison of CT and MR Imaging in Staging of Neck , 2005 .

[34]  J. Woolgar,et al.  The topography of cervical lymph node metastases revisited: the histological findings in 526 sides of neck dissection from 439 previously untreated patients. , 2007, International journal of oral and maxillofacial surgery.

[35]  Marcel van Herk,et al.  Target definition in prostate, head, and neck. , 2005, Seminars in radiation oncology.

[36]  Xavier Geets,et al.  Adaptive functional image-guided IMRT in pharyngo-laryngeal squamous cell carcinoma: is the gain in dose distribution worth the effort? , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[37]  Nico Karssemeijer,et al.  A novel iterative method for lesion delineation and volumetric quantification with FDG PET , 2007, Nuclear medicine communications.

[38]  J. Shirlaw.  THE METABOLISM OF TUMOURS , 1931 .

[39]  J Valk,et al.  Cervical lymph node metastasis: assessment of radiologic criteria. , 1990, Radiology.

[40]  C G Rowbottom,et al.  A novel imaging technique for fusion of high-quality immobilised MR images of the head and neck with CT scans for radiotherapy target delineation. , 2009, The British journal of radiology.

[41]  D. Visvikis,et al.  Impact of combined 18F-FDG PET/CT in head and neck tumours , 2005, British Journal of Cancer.

[42]  James F Dempsey,et al.  Determination and delineation of nodal target volumes for head-and-neck cancer based on patterns of failure in patients receiving definitive and postoperative IMRT. , 2002, International journal of radiation oncology, biology, physics.

[43]  B. Campbell,et al.  Clinical outcomes of patients receiving integrated PET/CT-guided radiotherapy for head and neck carcinoma. , 2008, International journal of radiation oncology, biology, physics.

[44]  Ursula Nestle,et al.  Target volume definition for 18F-FDG PET-positive lymph nodes in radiotherapy of patients with non-small cell lung cancer , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[45]  Kyle E. Rusthoven,et al.  The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor , 2004, Cancer.

[46]  D. Farina,et al.  Tumours of the oropharynx and oral cavity: perineural spread and bone invasion. , 1999, JBR-BTR : organe de la Societe royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie.

[47]  K. Strobel,et al.  FDG-positive Warthin's tumors in cervical lymph nodes mimicking metastases in tongue cancer staging with PET/CT , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[48]  David Schuster,et al.  Comparison of CT- and FDG-PET-defined gross tumor volume in intensity-modulated radiotherapy for head-and-neck cancer. , 2005, International journal of radiation oncology, biology, physics.

[49]  Srinivasan Vijayakumar,et al.  Development and validation of a standardized method for contouring the brachial plexus: preliminary dosimetric analysis among patients treated with IMRT for head-and-neck cancer. , 2008, International journal of radiation oncology, biology, physics.

[50]  G. Kubicek,et al.  FDG-PET staging and importance of lymph node SUV in head and neck cancer , 2010, Head & neck oncology.

[51]  Anne Bol,et al.  A gradient-based method for segmenting FDG-PET images: methodology and validation , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[52]  Fréderic Duprez,et al.  Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[53]  H. Kooy,et al.  Automatic three-dimensional correlation of CT-CT, CT-MRI, and CT-SPECT using chamfer matching. , 1994, Medical physics.

[54]  A R Hounsell,et al.  Geometrical analysis of radiotherapy target volume delineation: a systematic review of reported comparison methods. , 2010, Clinical oncology (Royal College of Radiologists (Great Britain)).

[55]  A. Scott,et al.  PET Changes Management and Improves Prognostic Stratification in Patients with Head and Neck Cancer: Results of a Multicenter Prospective Study , 2008, Journal of Nuclear Medicine.

[56]  M van Herk,et al.  The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer. , 1997, International journal of radiation oncology, biology, physics.

[57]  C. Evers,et al.  Incidence of small lymph node metastases with evidence of extracapsular extension: clinical implications in patients with head and neck squamous cell carcinoma. , 2009, International journal of radiation oncology, biology, physics.

[58]  C C Ling,et al.  Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. , 2000, International journal of radiation oncology, biology, physics.

[59]  Jason A Koutcher,et al.  Noninvasive assessment of tumor microenvironment using dynamic contrast-enhanced magnetic resonance imaging and 18F-fluoromisonidazole positron emission tomography imaging in neck nodal metastases. , 2010, International journal of radiation oncology, biology, physics.

[60]  F. Gallagher.  An introduction to functional and molecular imaging with MRI. , 2010, Clinical radiology.

[61]  L. Dawson,et al.  Recurrences near base of skull after IMRT for head-and-neck cancer: implications for target delineation in high neck and for parotid gland sparing. , 2004, International journal of radiation oncology, biology, physics.

[62]  P. Hofman,et al.  Morphological MRI criteria improve the detection of lymph node metastases in head and neck squamous cell carcinoma: multivariate logistic regression analysis of MRI features of cervical lymph nodes , 2008, European Radiology.

[63]  Ho-Fai Wong,et al.  18F-FDG PET and CT/MRI in oral cavity squamous cell carcinoma: a prospective study of 124 patients with histologic correlation. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[64]  Anne Bol,et al.  Tri-dimensional automatic segmentation of PET volumes based on measured source-to-background ratios: influence of reconstruction algorithms. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[65]  N. Lee,et al.  Recurrence in region of spared parotid gland after definitive intensity-modulated radiotherapy for head and neck cancer. , 2008, International journal of radiation oncology, biology, physics.

[66]  S. Hee,et al.  Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy-the national cancer centre singapore experience. , 2008, International journal of radiation oncology, biology, physics.

[67]  Sigrid Stroobants,et al.  Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with 18F-FDG PET, 18F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI , 2009, Journal of Nuclear Medicine.

[68]  Christine Kong,et al.  The value of magnetic resonance imaging in target volume delineation of base of tongue tumours--a study using flexible surface coils. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[69]  E. Escott.  Positron emission tomography-computed tomography protocol considerations for head and neck cancer imaging. , 2008, Seminars in ultrasound, CT, and MR.

[70]  Jeong Hyun Lee,et al.  Combined [18F]fluorodeoxyglucose positron emission tomography and computed tomography for detecting contralateral neck metastases in patients with head and neck squamous cell carcinoma. , 2011, Oral oncology.

[71]  Jatinder R Palta,et al.  Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  Jean-François Daisne,et al.  Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen. , 2004, Radiology.

[73]  K. Brock.  Results of a multi-institution deformable registration accuracy study (MIDRAS). , 2010, International journal of radiation oncology, biology, physics.

[74]  W. De Gersem,et al.  An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways. , 2001, International journal of radiation oncology, biology, physics.

[75]  P. Vernon,et al.  Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error? , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[76]  Marcel van Herk,et al.  Decreased 3D observer variation with matched CT-MRI, for target delineation in Nasopharynx cancer , 2010, Radiation oncology.

[77]  L. Peters,et al.  Clinical impact of, and prognostic stratification by, F‐18 FDG PET/CT in head and neck mucosal squamous cell carcinoma , 2007, Head & neck.

[78]  R. Wiggins,et al.  Comparison of Whole-Body PET/CT, Dedicated High-Resolution Head and Neck PET/CT, and Contrast-Enhanced CT in Preoperative Staging of Clinically M0 Squamous Cell Carcinoma of the Head and Neck , 2009, Journal of Nuclear Medicine.

[79]  B. Sanghera,et al.  Adaptive 18fluoro-2-deoxyglucose positron emission tomography/computed tomography-based target volume delineation in radiotherapy planning of head and neck cancer. , 2011, Clinical oncology (Royal College of Radiologists (Great Britain)).

[80]  A. Kuten,et al.  Fluorodeoxyglucose‐Positron Emission Tomography/Computed Tomography Imaging in Patients with Carcinoma of the Larynx: Diagnostic Accuracy and Impact on Clinical Management , 2006, The Laryngoscope.

[81]  A. Paulino.  PET-CT in Radiotherapy Treatment Planning , 2008 .

[82]  K. Soo,et al.  Radical neck dissections for squamous carcinomas: pathological findings and their clinical implications with particular reference to transcapsular spread. , 1987, International journal of radiation oncology, biology, physics.

[83]  Dwight E Heron,et al.  Hybrid PET-CT simulation for radiation treatment planning in head-and-neck cancers: a brief technical report. , 2004, International journal of radiation oncology, biology, physics.

[84]  R. Weber,et al.  FDG-PET staging of head and neck cancer--can improved imaging lead to improved treatment? , 2008, Journal of the National Cancer Institute.

[85]  N. Blumstein,et al.  Quantitative analysis of extracapsular extension of metastatic lymph nodes and its significance in radiotherapy planning in head and neck squamous cell carcinoma. , 2010, International journal of radiation oncology, biology, physics.

[86]  Johan Bussink,et al.  Clinical evidence on PET-CT for radiation therapy planning in head and neck tumours. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[87]  A. Riegel,et al.  Variability of gross tumor volume delineation in head-and-neck cancer using CT and PET/CT fusion. , 2005, International journal of radiation oncology, biology, physics.

[88]  Agnese Cecconi,et al.  Combined 18F-FDG-PET/CT imaging in radiotherapy target delineation for head-and-neck cancer. , 2009, International journal of radiation oncology, biology, physics.

[89]  Tomio Inoue,et al.  Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006-2007. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[90]  M. Mack,et al.  Iron oxide particle-enhanced magnetic resonance imaging for detection of benign lymph nodes in the head and neck: how reliable are the results? , 2007, Anticancer research.

[91]  Daniel A Low,et al.  A novel PET tumor delineation method based on adaptive region-growing and dual-front active contours. , 2008, Medical physics.

[92]  G. Weinstein,et al.  Prediction of Response to Chemoradiation Therapy in Squamous Cell Carcinomas of the Head and Neck Using Dynamic Contrast-Enhanced MR Imaging , 2010, American Journal of Neuroradiology.

[93]  A. King,et al.  The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis. , 2008, The British journal of radiology.

[94]  A. Eisbruch,et al.  Delineating neck targets for intensity- modulated radiation therapy of head and neck cancer. What we learned from marginal recurrences? , 2007, Frontiers of radiation therapy and oncology.

[95]  Jonathan G. Li,et al.  Patterns of failure and toxicity after intensity-modulated radiotherapy for head and neck cancer. , 2008, International journal of radiation oncology, biology, physics.

[96]  Eric J. W. Visser,et al.  Quantification of FDG PET studies using standardised uptake values in multi-centre trials: effects of image reconstruction, resolution and ROI definition parameters , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[97]  R. Hermans,et al.  Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[98]  M. Mack,et al.  Cervical lymph nodes. , 2008, European journal of radiology.

[99]  Sandra Nuyts,et al.  Head and neck squamous cell carcinoma: value of diffusion-weighted MR imaging for nodal staging. , 2009, Radiology.

[100]  S. H. Cheng,et al.  T classification and clivus margin as risk factors for determining locoregional control by radiotherapy of nasopharyngeal carcinoma , 1998, Cancer.

[101]  G. Marchal,et al.  Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR) – results of a phase-III multicenter clinical trial , 2002, European Radiology.

[102]  C. Rübe,et al.  Comparison of different methods for delineation of 18F-FDG PET-positive tissue for target volume definition in radiotherapy of patients with non-Small cell lung cancer. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[103]  C. Akman,et al.  The application of positron emission tomography/computed tomography in radiation treatment planning: effect on gross target volume definition and treatment management. , 2010, Clinical oncology (Royal College of Radiologists (Great Britain)).

[104]  C. Snyderman,et al.  Head and neck malignancy: is PET/CT more accurate than PET or CT alone? , 2005, Radiology.

[105]  G. Snow,et al.  Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study , 2004, European Archives of Oto-Rhino-Laryngology.

[106]  Srinivasan Vijayakumar,et al.  Marginal misses after postoperative intensity-modulated radiotherapy for head and neck cancer. , 2011, International journal of radiation oncology, biology, physics.

[107]  Bradford A Moffat,et al.  Evaluation of cancer therapy using diffusion magnetic resonance imaging. , 2003, Molecular cancer therapeutics.

[108]  Xavier Geets,et al.  Impact of the type of imaging modality on target volumes delineation and dose distribution in pharyngo-laryngeal squamous cell carcinoma: comparison between pre- and per-treatment studies. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[109]  A. Kuten,et al.  Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging in patients with carcinoma of the nasopharynx: diagnostic accuracy and impact on clinical management. , 2007, International journal of radiation oncology, biology, physics.

[110]  Anil Sethi,et al.  Influence of MRI on target volume delineation and IMRT planning in nasopharyngeal carcinoma. , 2003, International journal of radiation oncology, biology, physics.

[111]  Mithat Gonen,et al.  Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. , 2004, Radiology.

[112]  Tohru Shiga,et al.  Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas. , 2002, International journal of radiation oncology, biology, physics.

[113]  H. Huisman,et al.  Clinical validation of the normalized mutual information method for registration of CT and MR images in radiotherapy of brain tumors , 2004, Journal of applied clinical medical physics.

[114]  P. Levendag,et al.  Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[115]  Cornelis A T van den Berg,et al.  Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology. , 2011, International journal of radiation oncology, biology, physics.

[116]  R. Beets-Tan,et al.  Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma , 2009, Neuroradiology.

[117]  Johan Bussink,et al.  PET-CT for response assessment and treatment adaptation in head and neck cancer. , 2010, The Lancet. Oncology.

[118]  L. Ting,et al.  Impact of magnetic resonance imaging versus CT on nasopharyngeal carcinoma: primary tumor target delineation for radiotherapy , 2004, Head & neck.

[119]  J. Choi,et al.  Tumor Volume Assessment by 18F-FDG PET/CT in Patients with Oral Cavity Cancer with Dental Artifacts on CT or MR Images , 2008, Journal of Nuclear Medicine.

[120]  Vincent Grégoire,et al.  Regarding Davis et al.: Assessment of (18)F PET signals for automatic target volume definition in radiotherapy treatment planning. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[121]  X Allen Li,et al.  Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma. , 2006, International journal of radiation oncology, biology, physics.

[122]  K. Hirabayashi,et al.  Extracapsular spread of squamous cell carcinoma in neck lymph nodes: Prognostic factor of laryngeal cancer , 1991, The Laryngoscope.