Учебники / Head_and_Neck_Cancer_Imaging

ment tumor SUVs of > 4 were more likely to have persistent disease than those with SUVs < 4.

17.2.6 Prognostic Value

Recent data suggest that FDG uptake may have prognostic value in some tumors, including lung and breast cancer, because patients with high FDG uptake were observed to have a worse outcome. The potential value of FDG in predicting outcome in head and neck cancers, has been suggested in small series of patients.

Pretherapy FDG uptake (expressed as SUV) may be a useful parameter to identify those patients who should require more aggressive treatment.

Some recently published studies on primary tumors suggested that high FDG uptake may be an useful parameter for identifying particularly aggressive tumors. Allal et al. (2002) evaluated pre-therapy FDG uptake as a predictor of local control and dis- ease-free survival (DFS) after radiotherapy with or without chemotherapy in 63 head and neck SCC patients. In a multivariate analysis, SUV was found to be an independent predictor of DFS. Patients with high SUV (> 5.5) had significantly lower 3-year local control (55% vs. 86%) and DFS (42% vs. 79%) rates than patients with low SUV (< 5.5). Another study (Halfpenny et al. 2002) studied 58 patients with newly diagnosed SCC of the head and neck. They underwent FDG-PET before treatment. The median SUV value for all primary tumors was 7.16. Multivariate analysis demonstrated that an SUV > 10 provided prognostic information independent of the tumor stage and diameter. They conclude that high FDG uptake is an important marker for poor outcome in primary head and neck SCC.

Another study from Kitagawa et al. (2003) was prospectively conducted in 20 patients with head and neck cancer who completed the treatment regimen (neoadjuvant chemotherapy and concomitant radiotherapy) and underwent two FDG-PETs (one prior and one after treatment).Tumours with high pre-SUV (> 7) appeared to be more resistant to treatment. This may be because higher FDG uptake indicates greater cell viability or a higher propensity of cells to divide, or both (Haberkorn et al. 1991; Higashi et al. 1993). The data on FDG uptake in association with proliferative activity or with cellularity in malignant tumors are controversial. In clinical studies, cellularity rather than proliferative activity has been suggested to have a significant relationship to FDG.

There is currently no consensus of how the prognostic information derived from PET should influence the patient management. For this purpose, large scale prospective studies are needed in which the value of PET is compared to other molecular prognostic markers (such as p53 mutation, angiogenesis, hypoxia, Ki67, etc.).

17.3 Conclusion

FDG-PET has a good sensitivity and specificity for the detection of primary tumor in the head and neck and for nodal staging. PET-CT will probably be even more powerful than PET alone in the initial staging of head and neck cancer. FDG-PET can detect in a single examination distant metastases and second synchronous tumors. It can help in a significant number of patients to find the primary tumor in cases of neck metastases from an unknown primary.

FDG-PET is highly accurate in suspected tumor recurrence, even in asymptomatic patients. Across all studies, the negative predictive value is consistently high. Therefore, one could conclude that patients with a clinical suspicion of tumor recurrence and a negative FDG-PET scan do not require any further evaluation. A positive PET scan without any suspect morphologic correlate requires a biopsy; if the biopsy is negative for recurrent cancer and does not provide reasons for a false-positive PET, close clinical follow-up and a repeat biopsy may be required.

The treatment response to chemoand radiation therapy can be monitored with FDG-PET.

New emerging techniques or procedures, such as combining PET with sentinel node scintigraphy for staging the N0 neck, the use of FDG-PET in radiation treatment planning, and the use of PET for early prediction of treatment efficacy look very promising. However, further evaluation and standardization certainly is needed before the implementation in daily clinical practice.

The added value of the recent introduction of PET/CT as multimodality imaging tool in daily practice should not be underestimated in the head and neck region. It permits much better distinction between the different anatomic structures and decreases substantially the fraction of equivocal lesions, providing a higher diagnostic accuracy compared to PET alone, with or without visual comparison with CT images.

342

References

Adams S, Baum RP, Stuckensen T (1998). Prospective comparison of 18F-FDG-PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med 25:1255–1260

Allal AS, Dulguerov P, Allaoua M, et al. (2002) Standardized uptake value of 2-(18)F fluoro-2-deoxy-D-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy. J Clin Oncol 20:1398–1404

Balkissoon J, Rasgon BM, Schweitzer L (2004) Lymphatic mapping for staging of head and neck cancer. Semin Oncol 31:382–393

Benchaou M, Lehmann W, Slosman D, et al. (1996) The role of FDG-PET in the preoperative assessment of N-staging in head and neck cancer. Acta Otolaryngol 116:332–335

Branstetter BF 4th, Blodgett TM, Zimmer LA, et al. (2005) Head and neck malignancy: is PET/CT more accurate than PET or CT alone? Radiology 235:580–586

Brun E, Kjellen E, Tennvall J, et al. (2002) FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 24:127– 135

Cohade C, Osman M, Pannu HK, Wahl RL (2003) Uptake in supraclavicular area fat (“USA-Fat”): description on 18FFDG PET/CT. J Nucl Med 44:170–176

Collins BT, Gardner LJ, Verma Ak, et al. (1998) Correlation of fine needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of locally recurrent and metastatic head and neck neoplasia. Acta Cytol 42:1325–1329

Dahlbom M, Hoffman E, Hoh C, et al. (1992) Whole-body positron emission tomography: part 1. Methods and performance characteristics. J Nucl Med 33:1191–1199

Daisne JF, Sibomana M, Bol A, et al. (2003) Tri-dimensional automatic segmentation of PET volumes based on measured source-to-background ratios: influence of reconstruction algorithms. Radiother Oncol 69:247–250

Daisne JF, Duprez T, Weynand B, et al. (2004) Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen. Radiology 233:93–100

Dalsaso TA, Lowe VJ, Dunphy FR, et al. (2000) FDG PET and CT in evaluation of chemotherapy in advanced head and neck cancer. Clin Positron Imaging 3:1–5

Di Martino E, Nowak B, Hassan H, et al. (2000) Diagnosis and staging of head and neck cancer. Arch Otolaryngol Head Neck Surg 126:1457–1461

Geets X, Daisne JF, Gregoire V, et al. (2004) Role of 11-C-methio- nine positron emission tomography for the delineation of the tumor volume in pharyngo-laryngeal squamous cell carcinoma: comparison with FDG-PET and CT. Radiother Oncol 71:267–273

Goerres G, Hany TF, Kamel E, et al (2002) Head and neck imaging with PET and PET-CT: artefacts from dental metallic implants. Eur J Nucl Med 29:367–370

Goerres GW, Mosna-Firlejczyk K, Steurer J, et al. (2003) Assessment of clinical utility of F-18-FDG-PET in patients with head and neck cancer: a probability analysis. Eur J Nucl Med Mol Imaging 30:562–571

Goerres GW, Schmid DT, Bandhauer F, et al. (2004) Positron emission tomography in the early follow-up of advanced

C. Castaigne et al.

head and neck cancer. Arch Otolaryngol Head Neck Surg 130:105–109

Greven KE, Williams DW, Keyes JW, et al. (1994) Positron emission tomography of patients with head and neck carcinoma before and after high dose irradiation. Cancer 74:1355–1359

Greven K, Williams DW, McGuirt F, et al. (2001) Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer. Head Neck 263:942– 946

Haberkorn U, Strauss LG, Reisser C, et al. (1991) Glucose uptake, perfusion and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry. J Nucl Med 32:1548–1555

Haberkorn U, Strauss LG, Dimitrakopoulou A, et al. (1993) Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 34:12–17

Haberkorn U, Bellemann ME, Altmann A, et al. (1997) PET 2-fluoro-2-deoxy-D-glucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine. J Nucl Med 38:1215–1221

Halfpenny W, Hain SF, Biassoni L, et al. (2002) FDG-PET. A possible prognostic factor in head and neck cancer. Br J Cancer 86:512–516

Hamakawa L, Takemura K, Sumida T et al. (2000) Histological study on pN upgrading of oral cancer. Virchows Arch 437:116–121

Hermans R, Feron M, Bellon E, et al. (1998) Laryngeal tumor volume measurements determined with CT: a study on intraand interobserver variability. Int J Radiat Oncol Biol Phys 40:553–557

Higashi K, Clavo AC, Wahl RL (1993) In vitro assessment of 2- fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med 34:773–779

Jones T (1996) The imaging science of positron emission tomography. Eur J Nucl Med 23:807–813

Kao J, Hsieh J, Tsai S, et al. (2000) Comparison of 18-fluoro- 2-deoxyglucose positron emission tomography and computed tomography in detection of cervical lymph node metastases of nasopharyngeal carcinoma. Ann Otol Rhinol Laryngol 109:1130–1134

Kinahan PE, Townsend DW, Beyer T, et al. (1998) Attenuation correction for a combined 3D PET/CT scanner. Med Phys 25:2046–2053

Kitagawa Y, Sadato N, Azuma H, et al. (1999) FDG PET to evaluate combined intra-arterial chemotherapy and radiotherapy of head and neck neoplasms. J Nucl Med 40:1132– 1137

Kitagawa Y, Sano K, Nishizawa S, et al. (2003) FDG-PET for prediction of tumour aggressiveness and response to intraarterial chemotherapy and radiotherapy in head and neck cancer. Eur J Nucl Med 30:63–71

Kovács AF, Döbert N, Gaa J, et al. (2004) Positron emission tomography in combination with sentinel node biopsy reduces the rate of elective neck dissections in the treatment of oral and oropharyngeal cancer. J Clin Oncol 22:3973–3980

Kubota R, Yamada S, Kubota K, et al. (1992) Intratumoral distribution of fluorine-18-Fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 33:1972–1980

Kunkel M, Förster GJ, Reichert TE, et al. (2003) Detection of recurrent oral squamous cell carcinoma by 18F-2-fluoro-

Positron Emission Tomography in Head and Neck Cancer

deoxyglucose-positron emission tomography. Cancer 98:2257–2265

Lapela M, Eigtved A, Jyrkkio S, et al. (2000) Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer. Eur J Cancer 36:858–867

Lonneux M, Lawson G, Ide C, et al. (2000) Positron emission tomography with fluorodeoxyglucose for suspected head and neck tumor recurrence in symptomatic patient. Laryngoscope 110:1493–1497

Lowe VJ, Dunphy FR, Varvares M, et al. (1997) Evaluation of chemotherapy response in patients with advanced head and neck cancer using (F-18)fluorodeoxyglucose positron emission tomography. Head Neck 19:666–674

Lowe V, Kim H, Boyd JH, et al. (1999) Primary and recurrent early stage laryngeal cancer: preliminary results of 2-(Fluo- rine 18)fluoro-2-deoxy-D-glucose PET imaging. Radiology 212:799–802

Lowe VJ, Boyd JH, Dunphy FR, et al. (2000) Surveillance for recurrent head and neck cancer using positron emission tomography. J Clin Oncology 18:651–658

McGuirt W, Keyes J, Greven K, et al. (1995a) Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography. Laryngoscope 105:579–584

McGuirt WF, Williams III DW, Keyes Jr, et al. (1995b) A comparative diagnosis study of head and neck nodal metastasis. Laryngoscope 105:373–375

Minn H, Joensuu H, Ahonen A, et al. (1988) Fluorodexyglucose imaging: a method to assess the proliferative activity of human cancer in vivo comparison with DNA flow cytometry in head and neck tumors. Cancer 61:1776–1781

Minn H, Lapela M, Klemi PJ, et al. (1997) Prediction of survival with fluorine-18-fluorodeoxyglucose and PET in head and neck cancer. J Nucl Med 38:1907–1911

Nishiyama Y, Yamamoto Y, Yokoe K, et al. (2005) FDG PET as a procedure for detecting simultaneous tumours in head and neck cancer patients. Nucl Med Commun 26:239–244.

Pauwels E, McCready VR, Stoot JH, et al. (1998) The mechanism of accumulation of tumour-localising radiopharmaceuticals. Eur J Nucl Med 25:277–305

Pekkola-Heino K, Kulmala J, Grenman R (1992) Sublethal damage repair in squamous cell carcinoma cell lines. Head Neck 14:196–199

Porceddu SV, Jarmolowski E, Hicks RJ, et al. (2005) Utility of

343

positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck 27:175–181

Rege SD, Chaiken L, Hoh CK, et al. (1993) Change induced by radiation therapy in FDG uptake in normal and malignant structures of the head and neck: quantification with PET. Radiology 189:807–812

Sakamoto H, Nakai Y, Ohashi Y, et al. (1998) Monitoring of response to radiotherapy with fluorine-18 deoxyglucose PET of head and neck squamous cell carcinomas. Acta Otolaryngol Suppl 538:254–260

Schwartz DL, Rajendran J, Yueh B, et al. (2003) Staging of the head and neck squamous cell cancer with extended-field FDG-PET. Arch Otolaryngol Head Neck Surg 129:1173–1178 Schöder H, Yeung HWD (2004a) Positron emission imaging of head and neck cancer, including thyroid carcinoma. Semin

Nucl Med 34:180–197 (review)

Schöder H, Yeung HWD, Gonen M, et al. (2004b) Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology 231:65–72

Shuller DE, McGuirt WF, McCabe BF, et al. (1984) The prognostic significance of metastatic cervical lymph nodes. Laryngoscope 94:1086–1090

Strauss LG (1996) Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 23:1409–1415

Stoeckli SJ, Steinert H, Pfaltz M, et al. (2002) Is there a role for positron emission tomography with 18F-fluorode- oxyglucose in the initial staging of nodal negative oral and oropharyngeal squamous cell carcinoma. Head Neck 24:345–349

Syed R, Bomanji JB, Nagabhushan N, et al. (2005) Impact of combined (18)F-FDG PET/CT in head and neck tumours. Br J Cancer 92:1046–1050

Terhaard CH, Bongers V, van Rijk PP, et al. (2001) F-18-fluoro- deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/pharyngeal cancer. Head Neck 23:933–941

Warburg O. (1956) On the origin of cancer cells. Science 123:309–314

Young H, Baum R, Cremerius U, et al. (1999) Measurement of clinical and subclinical tumour response using 18Ffluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer 35:1773–1782

CONTENTS

18.1Introduction 345

18.2General Principles of Radiotherapy for Head

and Neck Cancer 346

18.3Present Status of Imaging Modalities

in Radiotherapy: Overview 348

18.3.1 Computed Tomography in Radiotherapy 349

18.3.1.1General Considerations 349

18.3.1.2Advantages 349

18.3.1.3Disadvantages 349

18.3.1.4Special Features 349

18.3.2 Magnetic Resonance Imaging in Radiotherapy 350

18.3.2.1General Considerations 350

18.3.2.2Advantages 350

18.3.2.3Disadvantages 350

18.3.2.4Use 350

18.3.3Positron Emission Tomography

in Radiotherapy 350

18.3.3.1General Considerations 350

18.3.3.2Advantages 351

18.3.3.3Disadvantages 351

18.3.3.4Use 351

18.4Applications of Imaging Data in Radiation Oncology 351

18.4.1 Target Delineation: Anatomical Information 351

18.4.1.1CT 351

18.4.1.2MRI 352

18.4.1.3PET 352

18.4.2 Target Delineation: Biological Information 353

18.4.2.1Hypoxia 354

18.4.2.2Proliferation 355

18.4.2.3Apoptosis 356

S. Nuyts, MD, PhD

Professor, Department of Radiation-Oncology, University

Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium

18.1 Introduction

Radiotherapy is used as part of the treatment in the majority of patients with head and neck cancer (HNC) during the course of their disease. In the last decade there have been important advances in the delivery of radiotherapy which have been made possible by the development of more powerful computers for treatment planning, delivery and data processing. The integration with better immobilisation of patients and advances in linear accelerator design such as multileaf beam collimators and on-line portal imaging systems, allow more accurate delivery of high radiation doses to the target volume while sparing the normal tissues. These developments imply, however, a more rigorous delineation of target volumes and organs at risk.

The greatest challenge for radiation therapy is to attain the highest probability of cure with the least toxicity. To attain this goal, all cancer cells should be encompassed with sufficient dose of radiation during each fraction, while simultaneously sparing the surrounding normal tissues. Therefore, exact identification of the tumour cells is necessary. Technical improvements in the application of computed tomography scans (CT), magnetic resonance imaging (MRI), ultrasound, positron emission scans (PET) and electronic portal imaging have greatly improved our ability to identify tumours.

Initially, surface anatomy and radiographs were used to delineate the treatment site. This implied large treatment fields, which encompass large amounts of normal tissue. In a second step, thanks to the advent of the simulator, internal bony landmarks could be used by the radiation oncologist to guide the field set-up. Treatment planning was performed in a single plane with doses displayed as isodose lines (Table 18.1). Over the past 10 years, image-guided radiotherapy (IGRT) has come to our attention and CT became routine. Tumours and organs at risk are contoured on the CT images and three-dimensional (3D) images of these structures are reconstructed. Doses are displayed as dose-volume histograms.

MRI is now the standard imaging modality to evaluate nasopharyngeal carcinoma and has complementary value in other localisations of HNC. These modalities still depend on morphologic information for diagnosis. Therefore, the use of (18) F-fluoro- 2-deoxy-D-glucose PET (18FDG-PET) has recently drawn attention as a useful and valuable diagnostic tool in tumour delineation which offers the opportunity to obtain functional information about the tumour. However, co-registration to CT in order to maintain geographic accuracy is necessary.

The development of these imaging tools made it possible to target the radiation more conformal to the tumour. High precision 3D-conformal radiotherapy and intensity modulated radiotherapy (IMRT) are nowadays being used to maximally cover the tumoral tissues and to maximally avoid the normal structures. The obvious advantages associated with sparing of the salivary glands have pushed IMRT in the standard treatment of HNC faster than other cancer sites.

Today,the use of functional imaging in radiotherapy is under investigation. Functional images show metabolic, physiologic, genotypic and phenotypic data that may improve target definition for radiation therapy.

This chapter will focus on recent advances in imaging, both anatomical and functional/molecular imaging techniques, as they apply to radiotherapy. Although a comprehensive description of the technical details of the imaging techniques is beyond the scope of this chapter, we will give a brief overview of the advantages/disadvantages of these various imaging modalities. This will be followed by a review of the current and potential applications of these technologies in radiation oncology. But first, a general view of radiotherapy in HNC will be given.

18.2

General Principles of Radiotherapy for Head and Neck Cancer

Radiotherapy plays a very important role in the management of patients with HNC. Most early-stage tumours can be cured by surgery or by irradiation

and both treatment modalities produce similar locoregional control rates. The selection of treatment modality depends on results regarding cosmetic and organ function, patient’s condition and preference. In advanced tumours, radiation treatment can be given concomitant with chemotherapy or can be complementary to surgery in order to obtain maximal locoregional control.

In radiotherapy, the dose of radiation that can be delivered to a tumour is limited by the damage caused to the surrounding normal tissues and the consequent risk of complications. Although radiation damages both normal and neoplastic cells, most normal tissues have a small advantage over cancers in their ability to recover from radiation injury. In curative treatment, this difference is amplified to obtain a therapeutic advantage by using multiple small dose fractions over a period of several weeks. The higher the dose delivered, the greater the risk of complications. However, the more normal tissue that can be spared, the greater the potential for escalating the tumour dose. Improvement in locoregional tumour control can be obtained by increasing the dose of radiation. This, however, implies physical and biological optimisation to prevent normal tissue damage. To achieve this optimal dose distribution in the tumour, while sparing the normal tissues, it is critical to accurately delineate the target volumes.

In routine practice in many centers, most head and neck cancers are treated with two-dimensional (2D) radiotherapy consisting of two lateral opposed portals encompassing the primary and the nodal areas, with a separate low neck portal for treatment of the supraclavicular nodes (Fig. 18.1). At some time during treatment, the portals are reduced to limit the radiation dose to the spinal cord. An additional boost is given to the primary tumour and to the grossly involved nodes. This technique has several limitations:

•Total radiation dose can not be increased above 70– 74 Gy in 2-Gy fractions without severe late toxicity.

•Salivary glands can not be spared, leading to permanent xerostomia.

•Large amounts of mucosa are being irradiated.

•Matching of the fields can be critical especially if the junction lies over gross disease.

a

b

Fig. 18.1a,b. Standard 2D radiation portals for HNC: two lateral opposed fields (a) and a lower anterior field (b). In this field setup, both parotid glands receive full dose radiation. GTV, gross tumour volume

These issues have led to the development of conformal or CT-based radiotherapy allowing truly 3D dose delivery to the tumour (Fig. 18.2). Planning systems can reconstruct the CT images to a 3D model of the patient. Amongst the software tools available, the ‘beam’s eye view’ display is probably the most used. It consists of a projection of the patient’s anatomy as seen from the localisation of the radiation source and thus shows which structures are present in the beam. Beam angles, collimator angles, table angles and field sizes can thus be optimised for each beam. Information on electron densities and tissue depths acquired by CT are necessary for dosimetric computation using appropriate heterogeneity corrections. Following international guidelines concerning dose prescription (ICRU International Commission for Radiation Units 50 & 62), a treatment plan is developed. Dose volume histograms reproduce which radiation doses are delivered to which percentage of the structures (both normal and tumoral) so the treating radiation oncologist can make a prediction of the tumour control probability (TCP) and the normal tissue complication probability (NTCP).

To improve dose distribution to the target even further, IMRT was introduced in clinical practice. As its name implies, IMRT allows us to modulate the intensity of each radiation beam, so each field may have one or more areas of high intensity irradiation, while other areas receive lower doses. By modulating the number of fields and the intensity within each field, radiation dose can be sculpt around the tumour (Fig. 18.2).

High precision 3D-conformal radiotherapy and IMRT present the opportunity to reduce radiation exposure to normal tissues and thereby diminish the extent of toxicity. The head and neck is an ideal site for conformal radiotherapy (3D-CRT and IMRT) due to the complex geometry of this area and the severity of radiation-associated toxicity. Frequently, the distance between either gross tumour volume (GTV) or areas at high risk for microscopic disease (clinical target volume CTV) and critical structures such as optic nerve, spinal cord, brainstem, salivary gland is no more then a few millimetres. In the past, it was extremely difficult to deliver a high radiation dose to the tumour while limiting the dose to an organ at risk just a few millimetres away. The toxicity from head and neck radiotherapy was therefore among the worst seen in radiotherapy. Toxicities are defined as acute or late; acute toxicities are seen during treatment and are usually self-limiting, late toxicities are seen months or years after treatment and are usually permanent. In head and neck radiotherapy most common acute side-effects are mucositis and its accompanying dysphagia and odynophagia, salivary changes and dermatitis. Late toxicities include xerostomia, fibrosis, myelitis and osteonecrosis.

Because of the potential to escalate the dose to the tumour with the aim to improve the locoregional control and to decrease dose to normal tissue and thus reduce toxicity, 3D-CRT and IMRT are introduced in the treatment of HNC, thanks to the progress made in cancer imaging. These new developments, however, imply the risk of geographical misses if tumour delineation is not adequate. Expertise in the knowledge of the anatomy of the head and neck region, clinical examination, knowledge about the regional tumour spread, and interpretation of diagnostic imaging are therefore of major importance.

Another requisite of appropriate dose delivery is optimal patient positioning and immobilisation. In head and neck radiotherapy, masks are used which are fixed to the treatment table to prevent movement of the patient during therapy. This assures the ability to re-establish this position on a daily basis. Planning CT images, taken with the patient in treatment posi-

tion, with the patient wearing his or her mask, and on a flat table top are used for delineation of the tumour and organs at risk.

During treatment, target positioning and treatment verification is necessary. The size and shape of the treatment portal can be checked by using the ionising irradiation exiting from the irradiated patient. Adapted radiographic films are commercially available for that purpose. The image quality is less than diagnostic radiographs, but improvements have been made by the development of electronic portal imaging (EPI). Here, fluorescent screens, 2D ion chambers or matrix flat panel imagers are used. These online electronic images have made it possible to check and correct patient positioning before a significant amount of radiation is given (Fig. 18.3).

These recent developments in the use of imaging techniques in head and neck radiotherapy have made it necessary for the radiation oncologist to have excellent knowledge about the use,advantages and disadvantages, as well as interpretation of these different modalities.

18.3

Present Status of Imaging Modalities in Radiotherapy: Overview

The imaging modalities in radiation oncology can be divided into two main categories: anatomical imaging modalities, which provide structural or morphological information, and functional imaging modalities,

a

which elucidate the biological or molecular features of tissue. The general features of the imaging modalities are summarized in Table 18.2.

18.3.1

Computed Tomography in Radiotherapy

18.3.1.1

General Considerations

The opportunity to develop more conformal radiotherapy, thanks to the use of CT images, has led to an exponential increase in the use of CT in radiotherapy planning. The development of spiral CT and multi-slice CT leading to reduced examination times, and increased resolution has greatly enhanced the usefulness of CT in tumour detection and delineation. Nowadays, high-quality multiplanar imaging is feasible with CT.

18.3.1.2 Advantages

•Good contrast between air, fat and bone.

•High spatial resolution.

•Widespread availability, (relatively) inexpensive.

•Good geometric accuracy.

•Visualization of bony anatomy for comparison with radiographs.

•Potential for rapid scanning.

•Contrast agents can improve tumour detection and delineation.

•Electronic density mapping availability.

b

Fig. 18.3a,b. Comparison between digitally reconstructed radiograph (a) and portal image (b). The digitally reconstructed radiograph is reconstructed based on CT images taken in treatment position. The corresponding portal image is obtained during irradiation. Both images are compared to one another to verify patient positioning and size and shape of the treatment portal

Table 18.2. Characteristics of various imaging modalities

18.3.1.3 Disadvantages

•Differentiation between tumour margins and adjacent normal tissue.

•Contrast agents and scattering caused by for example tooth fillings affect the signal intensity of the tissues and hamper the possibility to convert the signal to true tissue electron density.

18.3.1.4

Special Features

•Patient position must ensure immobilisation and be reproducible.

•The couch top must be the same as the treatment couch.

•Radio-opaque markers used to indicate skin reference marks.

•Between 2- and 10-mm thick slices depending on site.

•Ideally networked to planning computer to enable direct data transfer.

•Accurate calibration of CT numbers for inhomogeneity corrections.

•CT may be used to define a conformal treatment volume from digitally reconstructed radiographs.

18.3.2

Magnetic Resonance Imaging in Radiotherapy

18.3.2.1

General Considerations

MRI provides multi-planar anatomical information with high spatial and contrast resolution.

18.3.2.2 Advantages

•No patient radiation dose

•Excellent soft tissue delineation

•Vast flexibility in imaging protocols allowing optimalisation of image quality according to the tissue of interest

•Functional imaging capabilities

•Molecular imaging capability (e.g. spectroscopy)

•MRI-visible markers (e.g. oil-filled plastic tubes) to indicate skin reference marks

•High spatial resolution (<1 mm)

18.3.2.3 Disadvantages

•No inhomogeneity information available for treatment planning

•Patient positioning may be a problem as scanner aperture is usually small

•Long scan times

•Geometrical distortion must be corrected

18.3.2.4 Use

Today, most treatment planning is based on CT images only. Only for specific sites like nasopharyngeal and paranasal sinus cancers, MRI is used as an adjunct to CT (Fig. 18.4).

18.3.3

Positron Emission Tomography in Radiotherapy

18.3.3.1

General Considerations

Availability of more radionuclides and technological advances in PET scanning have increased the interest in using this modality in radiotherapy treatment planning. PET scanning results in biochemical information. Deoxyglucose labelled with fluorine (FDG)

Fig. 18.4. Example of CT/MRI fusion image. A 48-year-old male presented with a tumor recurrence of a squamous cell carcinoma of the facial skin with perineural spread along the infraorbital nerve into the fossa pterygopalatina, with further extension to the lateral wall of the left cavernous sinus (arrow). The diagnostic MRI was fused to the CT in treatment position to delineate the perineural spread

is frequently used to assess functional tumour metabolism.

Several studies have shown that FDG-PET might be better than CT or MRI at detecting cervical involved lymph nodes in HNSCC (Laudenbacher et al. 1995; Adams et al. 1998). The average sensitivity and specificity of PET was 84% and 96%, respectively, compared to 69% and 68%, respectively, for CT/MRI. However, other studies show that FDG-PET offers little additional information over CT and MRI (Stoeckli et al. 2002; Benchaou et al. 1996). These negative studies showed similar sensitivity and specificity for both FDG-PET and CT/MRI. All studies show, however, that the specificity of PET is high, around 90%. The sensitivity for PET to detect small lesions, is however a limitation. Brink et al. (2002) showed a sensitivity of 83% of PET to detect nodes larger than 1 cm3, but for smaller nodes the sensitivity dropped to 71%.

Many new radiopharmaceuticals are under development.

18.3.3.2 Advantages

•Metabolic/biologic data will be useful to define the biological target volume (BTV).

•Visualize the viable part of tumours.

•Detection of metastasis.

•Differentiate fibrous tissue from the residual mass after radiotherapy or chemotherapy.

18.3.3.3 Disadvantages

•False positive results with FDG-PET (physiological tracer uptake and uptake in inflammatory tissue).

•Lower spatial resolution compared with CT and MRI (about 2–7 mm), leading to false negative results.

•Anatomical localization may be difficult.

18.3.3.4 Use

It is mandatory to register these functional studies with either CT or MR data, in order to define the clinical target volume, that will be used afterwards in radiotherapy planning.

18.4

Applications of Imaging Data in Radiation Oncology

Imaging of tumours and surrounding normal tissues is used for several purposes related to radiation therapy:

•Medical diagnosis, including detection, staging and grading.

•Planning: to determine the treatment fields, we need to delineate the target and organs at risk. Both anatomical and biological imaging modalities are applied.

•Treatment guiding and verification: ensure that the field of irradiation is appropriate throughout the entire treatment period, taking into consideration factors such as:

Changes in tumour size and shape

Patient positioning variation

Variation in anatomy

Organ motion

All leading to intraand inter-fraction targeting errors

•Evaluation of response to therapy and follow up:

Anatomical changes

Functional changes

In the following, we will focus on improved target delineation and treatment verification based on imaging techniques. Combinations of two or more imaging modalities (including ‘image fusion’) are increasingly important, since complementary information can be provided.

18.4.1

Target Delineation: Anatomical Information

Optimal delineation of the primary tumour and the involved lymph nodes are a prerequisite to perform curative radiotherapy in head and neck cancer. Functional imaging can hereby complement anatomical imaging. In the planning of radiation therapy, it is important to localize the most peripherally located tumour cells, in order to irradiate the tumour tissue as precisely as possible, while sparing the normal, adjacent tissue. Improvement of target definition is therefore one of the most critical steps towards improvement in radiation therapy.

18.4.1.1 CT

CT is at present routinely used for initial delineation of tumour volumes and is considered to be the gold standard. However, both interand intraobserver variability in both GTV and CTV delineation exists. Hermans et al. (1998) investigated the interand intraobserver variability of CT based volume measurement of 13 laryngeal tumours by five different observers, who repeated the delineation four different times. They found that both interobserver variability and, to a lesser extent, intraobserver variability had a statistically significant effect on volume measurement. They also found that the most experienced observer obtained the most stable mean tumour volume over all sessions. This led them to conclude that variability in the CT-based volume measurements can be reduced by having the measurements done by a single experienced observer. However, this is not evident since not all radiation oncologists are evenly talented in CT image interpretation. Several groups have therefore published guidelines on both delineation of primary tumour CTV and nodal regions, based on CT images (Eisbruch et al. 2002; Gregoire et al. 2003; Chao et al. 2002).