Practical Essentials of Intensity Modulated Radiation Therapy, 3 Ed.

6. Nasopharynx

Tony J. C. Wang • K. S. Clifford Chao

Nasopharyngeal Cancer – Highlights

Key Recent Clinical Studies

Lin et al. (NEJM 2004) demonstrated that pretreatment EBV DNA may reflect microscopic residual tumor and was useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment. (PMID 15190138)

Kam et al. (JCO 2007) and Pow et al. (IJROBP 2006) showed in their phase III studies that early-stage nasopharyngeal carcinoma treated with IMRT alone showed improvement in xerostomia without compromising local control. (PMID 17971582 and PMID 17145528)

New Target Delineation Contours

FIGURE 6-12. CTV1, CTV2, and CTV3 delineation in a patient with clinically T2N3aM0 left nasopharyngeal carcinoma who received definitive IMRT.

1. ANATOMY

• The nasopharynx is roughly cuboidal; its borders are the posterior choanae anteriorly, the body of the sphenoid superiorly, the clivus and first two cervical vertebrae posteriorly, and the soft palate inferiorly (Fig. 6-1).

• The lateral and posterior walls are composed of the pharyngeal fascia, which extends outward bilaterally along the undersurface of the apex of the petrous pyramid just medial to the carotid canal. The roof of the nasopharynx slopes downward and is continuous with the posterior wall.

• The eustachian tube opens into the lateral wall; the posterior portion of the eustachian tube is cartilaginous and protrudes into the nasopharynx, making a ridge just posterior to the torus tubarius. Just posterior to the torus is a recess called Rosenmüller fossa.

• The roof and the posterior wall of the nasopharynx consist of the clivus and basisphenoid, which are the foundation of the central skull base and cavernous sinus; the bony portion of the eustachian tube lies lateral to the carotid canal.

• Many foramina and fissures are located in the base of the skull, through which several structures pass (Table 6-1). Some are potential routes of spread of nasopharyngeal carcinoma (Fig. 6-2).

• The jugular fossa, which lies just posterior to the carotid foramen, is usually larger on the right side. The jugular spur separates the pars nervosa from the pars venosum of the fossa.

• Cranial nerve IX lies within the pars nervosa of the jugular fossa, whereas cranial nerves X through XII lie within the pars venosum along with the jugular vein.

• The base of the pterygoid plates is part of the basisphenoid; the pterygopalatine fossa lies between the pterygoid processes and the maxillary sinus and is contiguous with the inferior orbital fissure superiorly and the infratemporal fossa laterally. The foramen rotundum can be seen just above the base of the pterygoid processes.

• The upper pharyngeal musculature attaches to the basisphenoid and styloid process. Levator and tensor veli palatini muscle attachments are visualized along the inferior petrous apex and basisphenoid, respectively.

• An extensive submucosal capillary lymphatic plexus exists in the nasopharyngeal region. This can explain the high incidence of neck node metastasis at initial presentation of patients. The tumor initially spreads to the retropharyngeal, junctional, and jugulodigastric lymph nodes, and then along the internal jugular and spinal accessory chains. Incidence and distribution of clinically positive neck nodes in nasopharyngeal carcinoma are shown in Table 6-2.1

FIGURE 6-1. (A) Nasopharynx and related structures in the midsagittal section of the head. (From Agur AMR, Dailey AF. Grant’s Atlas of Anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:694, with permission.)

FIGURE 6-1. (B) Medial section of the head and neck. (From Moore KL, Dalley AF. Clinical Oriented Anatomy, 4th ed. Baltimore, MD: Lippincott Williams & Wilkins, 1999.)

• Lymphatics of the nasopharyngeal mucosa run in an anteroposterior direction to meet in the midline; from there, they drain into a small group of nodes lying near the base of the skull in the space lateral and posterior to the parapharyngeal or retropharyngeal space. This group lies close to cranial nerves IX, X, XI, and XII, which run through the parapharyngeal space (Fig. 6-2B,C).

• Figure 6-3 shows a drawing of the nasal cavity and nasopharynx and also an axial MRI of the same structures.

• The retropharyngeal lymph nodes are an important route of spread. The lateral retropharyngeal lymph nodes are located in the retropharyngeal space near the lateral border of the posterior pharyngeal wall and medial to the carotid artery. Directly behind them (Rouviere nodes) are the lateral masses of the atlas (C1). Usually one node occurs on each side, but occasionally two and very rarely three are found, and they can be found even at the level of the hyoid bone (C3). These nodes atrophy with age and may be absent unilaterally, but are rarely absent entirely. Incidence of retropharyngeal lymphadenopathy in nasopharyngeal cancers is shown in Table 6-3.

• Clinically, lymph nodes of the parotid area may also be involved. This route of spread is possible from the lymphatics of the eustachian tube, which may drain by way of the lymph vessels of the tympanic membrane and external auditory canal to the periparotid lymph nodes.

• Another lymphatic pathway from the nasopharynx leads to the deep posterior cervical node at the confluence of the spinal accessory and jugular lymph node chains.6

• A third pathway is to the jugulodigastric node, which is frequently involved in nasopharyngeal carcinoma, according to Lederman.7

2. NATURAL HISTORY

• Carcinoma of the nasopharynx frequently arises from the lateral wall, with a predilection for the fossa of Rosenmüller and the roof of the nasopharynx.

• Tumor may involve the mucosa or grow predominantly in the submucosa, invading adjacent tissues including the nasal cavity. In approximately 5% of patients, tumor may extend into the posterior or medial walls of the maxillary antrum and ethmoids.

• In more advanced stages, tumor may involve the oropharynx, particularly the lateral or posterior wall.

• Superior extension of tumor through the foramen lacerum may result in cranial nerve involvement and destruction of the middle fossa (Figs. 6-2 and 6-4).

• Figure 6-5 graphically illustrates typical patterns of spread in nasopharyngeal cancer.

• The floor of the sphenoid may occasionally be involved.

• Approximately 90% of patients develop lymphadenopathy, which is present in approximately 70% at initial diagnosis.8

• The American Joint Commission on Cancer (AJCC) 2010 staging has some notable changes including the removal of prior T2a disease which is now T1, and therefore stage IIA is now part of stage I. Furthermore, unilateral or bilateral retropharyngeal nodes are classified as N1.

• The incidence of distant metastasis is not related to the stage of the primary tumor, but correlates strongly with the degree of cervical lymph node involvement. In 63 patients with N0 neck, 11 (17%) developed metastatic disease, in contrast to 69 of 93 (74%) with N3 cervical lymphadenopathy.9 The most common site of distant metastasis is bone, followed by lung and liver.10

FIGURE 6-2. (A) Cranium, inferior views. (From Agur AMR, Dalley AF. Grant’s Atlas of Anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:616.)

FIGURE 6-2. Cranium, inferior view. Ibid., 617.

FIGURE 6-2. (B) Superior view of the interior of the base of the skull showing the cranial nerves, dura mater, and blood vessels. On the left side, the dura is cut away to expose the trigeminal cave (cavity) housing the trigeminal ganglion and its roots and the nerves arising from it: CN V1, CN V2, and CN V3. The cerebellar tentorium (L. tentorium cerebelli) is also removed on the left side to show the nerves exiting the internal acoustic meatus (CN VII and CN VIII) and jugular foramen (CN IX, CN X, and CN XI), as well as the transverse and superior petrosal dural venous sinuses. (From Moore KL, Dalley AF II. Clinical Oriented Anatomy, 4th ed. Baltimore, MA: Lippincott Williams & Wilkins, 1999.)

3. DIAGNOSIS AND STAGING SYSTEM

3.1. Signs and Symptoms

• Tumor growth into the posterior nasal fossa can produce nasal obstruction, discharge, or epistaxis. In some cases, the voice may develop a nasal twang.

• The orifice of the eustachian tube can be obstructed by a relatively small tumor; ear pain or a unilateral decrease in hearing can occur. Sometimes blockage of the eustachian tube may produce a middle ear transudate.

• Headache or pain in the temporal or occipital region can occur. Proptosis sometimes results from direct extension of tumor into the orbit.

• Sore throat can occur when tumor involves the oropharynx.

• Although a neck mass elicits medical attention in only 18% to 66% of cases, clinical involvement of cervical lymph nodes on examination at presentation ranges from 60% to 87%.7,11

• Some patients present with cranial nerve involvement. In 218 patients, 26% had cranial nerve involvement, but it was present at initial diagnosis in only 3% of patients.7 Leung et al. reported a 12% incidence of cranial nerve involvement in 564 patients with primary nasopharyngeal carcinoma; it was higher in patients staged with computed tomography (CT) (52 of 177, 29%).12

FIGURE 6-2. (C) Illustration of cranial nerves and the functions they control. (From Rubin P, Hansen JT. TNM Staging Atlas with Oncoanatomy, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2012:15.)

• Cranial nerves III through VI are involved by extension of tumor up through the foramen lacerum to the cavernous sinus. Cranial nerves VII, VIII, and I are rarely involved (Figs. 6-2C and 6-4).

3.2. Physical Examination

• The flexible fiberoptic nasopharyngolarnygoscope is the main tool to completely examine the upper aerodigestive tract including the nasopharynx. Early lesions mostly occur on the lateral walls or roof of the nasopharynx.

• In early cases, only slight fullness in the Rosenmüller fossa or a submucosal bulge or asymmetry in the roof may be the only evidence of disease. Lymphomas and minor salivary gland tumors have a tendency to remain submucosal until gross progression.

• The site of origin is rarely the nasopharyngeal surface of the soft palate, nor is it often invaded secondarily, even by advanced tumors.

• Nasoscopes may aid us by showing tumor growth into the anterior and superior portions of the nasal cavity. Tumor may be seen submucosally infiltrating along the posterior tonsillar pillars and occasionally down the posterior pharyngeal wall.

• Palpation of neck nodes and measuring the size and lowest extent of lymphadenopathy are important.

• Evaluation of the cranial nerves is essential. The fifth and sixth cranial nerves are most commonly involved. Otitis media and decreased hearing can be found on ear examination. Table 6-4 summarizes functions of the cranial nerves, which should be examined during the initial consultation.

3.3. Imaging

• Imaging evaluation is necessary for staging and treatment planning in all nasopharyngeal carcinomas as well as in posttreatment evaluation.

• The main imaging tools of the nasopharyngeal region are CT, magnetic resonance imaging (MRI), and positron emission tomography (PET).

• CT scan thickness should be 3 mm or less for treatment planning. The normal anatomy of the nasopharynx as seen on CT is shown in Figure 6-6.

• Unless medically contraindicated, MRI is the preferred primary examination for disease in the nasopharynx, which provides higher sensitivity for deep tumor infiltration (Figs. 6-7 and 6-8).13

• The neck is always included when imaging is performed. Coronal and sagittal sections should be evaluated for all imaging modalities.

• The torus tubarius, eustachian tube orifice, and fossa of Rosenmüller are often asymmetric in appearance. Lymphoid tissue has a tendency to atrophy with age, which can be responsible for superficial contour variation of the nasopharyngeal region. Lymphoid tissue is better visualized with MRI.

• The carotid artery and jugular veins should always be clearly visible in the poststyloid parapharyngeal space, along with at least some surrounding fatty tissue. The intervening cranial nerves IX through XII and the sympathetic chain can sometimes be seen in high-resolution MRI.

• The retropharyngeal lymph nodes are visible on MRI medial to the carotid artery at the border between the poststyloid parapharyngeal and retropharyngeal spaces (Fig. 6-9A,B). The nodes are normally 3 to 5 mm in size in adults and 10 to 15 mm in infants and children.

• The fifth nerve ganglion, within Meckel’s cave, and its branches both inside and outside the cavernous sinus are easily recognized on good-quality MRI and CT.

• The third, fourth, and sixth cranial nerves, along with the first division of the trigeminal nerve, are best visualized on coronal MRI as they go through the wall of the cavernous sinus.

• The fat within nasopharyngeal spaces is normally symmetric, although the size of vessels coursing through the spaces may vary slightly; obliteration of fat in MRI or CT is a sign of pathologic involvement.

FIGURE 6-3. Transverse section and MR imaging of nasal cavity and nasopharynx (A) Transverse section of the left side of the head (B) Transverse (axial) MRI scan. (From Agur AMR, Dalley AF. Grant’s Atlas of Anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:720.)

• The third division of the trigeminal nerve exiting the foramen ovale is often seen on MRI.

• Perineural enhancement within the cranial nerve exit and the foramina and prominent enhancement of venous plexuses just below the skull base are normal variants.

3.4. Staging

• There have been some changes in the latest AJCC 2010 staging system from the previous AJCC 2002 staging system. Previous T2a lesions are now designated as T1; therefore stage IIA will now be stage I. Lesions previously staged as T2b are now T2 and therefore stage IIB is now designated as stage II.

• Retropharyngeal lymph nodes are considered N1, regardless of unilateral or bilateral location. The prognostic value was similar to that of unilateral cervical involvement.14

4. PROGNOSTIC FACTORS

• Epidemiological factors: Race, age, and gender have prognostic significance.5 Perez et al. found that patients younger than 50 years had better survival and local control.1 Sham and Choy found similar results in their retrospective analysis of 759 patients.15

• Stage: Sham and Choy and Perez et al. showed stage as a significant factor determining survival and local control.1,15

• Cranial nerve involvement: This was significantly associated with decreased survival in several series. Lee et al., Sham and Choy, and Perez et al. found it to be a significant prognostic factor.1,15,16 However, Chu et al. did not conclude that it was a prognostic factor.17

• Lymph node metastasis: Survival decreases as cervical lymph node involvement progresses from the upper to the middle and lower nodes.8

• Bilateral cervical lymph node involvement: Bilateral neck node metastasis was found to be an ominous prognostic factor by Lee et al., demonstrating that bilaterality was associated with a higher risk of nodal failure.16 However, Sham and Choy did not find bilaterality to be a prognostic factor.15

• Histology: In 122 patients with localized nasopharyngeal carcinoma, histology was the most important prognostic factor for survival; the relative risk of death was 3.4 and 3.2 times higher for nonkeratinizing and squamous cell carcinoma, respectively, compared with undifferentiated carcinoma.16,18 On the other hand, others noted no difference in survival or incidence of distant metastasis between keratinizing and nonkeratinizing squamous cell carcinomas.1,16

• Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) levels have been shown to have prognostic value, particularly in the posttreatment setting.1921

5. GENERAL MANAGEMENT

• Because the nasopharynx is immediately adjacent to the base of the skull, surgical resection with an acceptable margin is often not achievable. Depending on the extent of disease, radiation therapy and chemoradiation have been the standard treatment for nasopharyngeal carcinoma.

• Rarely, radical neck dissection has been performed for treatment of neck node metastasis, but it is not superior to irradiation alone. The rate of metastatic spread to the level I–V neck nodes is given in Table 6-2.

• The standard management for stage I nasopharyngeal carcinoma is radiotherapy alone. Results from modern studies have shown excellent local control and overall survival at approximately 90%.22 Two phase III studies of early-stage nasopharyngeal carcinoma treated with IMRT alone showed improvement in xerostomia without reducing local control.23,24

FIGURE 6-4. Nerves and vessels of the middle cranial fossa. (A) Superficial dissection. The tentorium cerebelli is cut away. The dura mater is largely removed from the middle cranial fossa. The roof of the orbit is partly removed. (B and C) Coronal sections through the cavernous sinus. (From Agur AMR, Dalley AF. Grant’s Atlas of Anatomy, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009:644.)

FIGURE 6-5. Patterns of spread. (A) Sagittal view notes extensions into oropharynx and parapharyngeal invasion. (B) Coronal view notes invasion of the skull base, cavernous sinus, and cranial nerves. The primary cancer (nasopharynx) invades in various directions which are color-coded vectors (arrows) representing stages of progression: Tis, yellow; Tl, green; T2, blue; T3, purple; T4, red. (From Rubin P, Hansen JT. TNM Staging Atlas with Oncoanatomy, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2012:43.)

• Stage II nasopharyngeal carcinoma should be managed with chemoradiation therapy. A phase III trial randomized stage II nasopharyngeal carcinoma patients to radiotherapy alone versus radiotherapy with concurrent chemoradiation. With a median follow-up of 5 years, the study showed better overall survival and distant metastasis-free survival with chemoradiation.25

• Intergroup 0099 was one of the earliest phase III trials demonstrating advantage of chemoradiation versus radiotherapy alone in patients with stage III or stage IV nasopharyngeal cancer.26 Radiotherapy was administered in both arms for a total dose of 70 Gy by conventional techniques. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy. After completion of radiotherapy, patients received additional postradiotherapy and chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/day on days 1 to 4 every 4 weeks for three courses. The 3-year progression-free survival rate was 24% versus 69% in favor of the chemotherapy arm (P < 0.001). The 3-year overall survival rate was 47% and 78%, respectively (P = 0.005).

• A total of 10 phase III trials comparing chemoradiation versus radiotherapy alone have been published. Seven of these trials have demonstrated an overall survival benefit with chemoradiation and are shown in Table 6-5.2534

• These phase III trials have confirmed the role of chemoradiation as the standard of care for locally advanced nasopharyngeal carcinoma.

• The role of adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma has recently been questioned. A phase III study randomized 508 patients with locally advanced disease to concurrent chemoradiation followed by adjuvant chemotherapy or observation. With a median follow-up of 38 months, there was no difference in failure-free survival.35

• Many studies have reported the efficacy of IMRT for nasopharyngeal carcinoma and the outcomes are shown in Table 6-6.

FIGURE 6-6. (A–C) Anatomic line diagrams showing the different levels of the nasopharyngeal region, to correlate with the accompanying CT images at the same level.

FIGURE 6-7. (A) Axial contrast-enhanced CT showing nothing extending laterally to the line drawn between the medial pterygoid plate (thin arrow) and the lateral aspect of the carotid artery (short arrow). (B) Axial contrast-enhanced T1-weighted MRI showing that tumor had broken pharyngobasilar fascia (arrow). (From Liao et al. Int J Radiat Oncol Biol Phys 2008;72:1368–1377, with permission.)

• Neoadjuvant or adjuvant chemotherapy has been used to treat primary or recurrent nasopharynx cancer with complete response rates of 10% to 20% and partial response rates of 40%. Recently, significant impact on long-term survival has been reported.

• These phase III studies showed that concurrent chemotherapy followed by adjuvant chemotherapy yielded better therapeutic results in advanced nasopharyngeal carcinoma. Another important conclusion is that concurrent use of cisplatin during radiotherapy is essential, and chemotherapy, which is given either neoadjuvant or adjuvant to radiotherapy, has only little or no benefit in advanced nasopharyngeal carcinoma if given without concomitant cisplatin.

• A meta-analysis of 1,753 patients from eight randomized trials has shown that the addition of chemotherapy to radiotherapy for locoregionally advanced nasopharyngeal cancer increases both absolute event-free and overall survival by 10% and 6%, respectively, at 5 years. The maximum effect was seen with concurrent chemoradiotherapy.55

6. INTENSITY-MODULATED RADIATION THERAPY IN NASOPHARYNGEAL CARCINOMA

6.1. Target Volume Determination

• If chemotherapy was delivered before radiation, the targets should be outlined on the planning CT according to their prechemotherapy extent.

• Because of the high likelihood of cervical metastasis, most authors recommend electively treating all of the cervical lymphatics in N0 patients; it should be noted that sparing of level IB can be considered.

FIGURE 6-8. Axial contrast-enhanced CT of the nasopharynx in a patient with nasopharyngeal carcinoma. (A) No obvious soft-tissue mass enhanced by contrast medium (curved arrow). (B) Axial T2-weighted MRI of the same patient showing tumor invading left prevertebral muscle (hollow arrow). (From Liao et al. Int J Radiat Oncol Biol Phys 2008;72:1368–1377.)

• Lymph node groups at risk in the nasopharyngeal region include the following:

a. Submandibular nodes (surgical level I): if any node is involved.

b. Upper deep jugular (junctional, parapharyngeal) nodes: all cases.

c. Subdigastric (jugulodigastric) nodes, midjugular, lower neck, and supraclavicular nodes (levels II through IV): all cases, bilaterally.

d. Posterior cervical nodes (level V): all cases, bilaterally.

e. Retropharyngeal nodes: all cases, bilaterally.

• The target volume specification for definitive and postoperative intensity-modulated radiation therapy (IMRT) in nasopharyngeal cancer is summarized in Table 6-7.

• CTV1 (high-risk volume) includes all primary and nodal gross tumor volume (GTV) with a 10-mm margin. May consider omitting air, skin, bone, and optic pathway structures if not invaded by tumor. Gross nodal disease >1 cm or FDG avid should also be included.

FIGURE 6-9. (A) Coronal and sagittal MRI sections showing a T4 nasopharyngeal carcinoma invading the base of the skull (arrows).

FIGURE 6-9. (B) Coronal and sagittal MRI sections showing tumor extent in a nasopharyngeal carcinoma patient.

• CTV2 (intermediate-risk volume) includes a 5-mm margin on CTV1. For T3/T4 disease, the superior margin extends to include the complete sphenoid sinus. For T1/T2 disease, the superior margin extends to the floor of the sphenoid sinus.

• Include the lateral extension to the mandibular ramus and all pterygoid muscles on the involved side to the mandibular ramus. Split the pterygoid muscles on the uninvolved side.

• Nodal CTV2 includes medial retropharyngeal nodes inferior to the superior edge of the hyoid bone. Nodal CTV2 of the involved neck extends up to the base of the skull.

• Nodal CTV2 extends inferiorly to the sternoclavicular joint when the lower neck is treated with IMRT.

• CTV2 should include high-risk subclinical disease which covers the entire nasopharynx, anterior clivus, skull base, inferior sphenoid sinus, cavernous sinus, pterygoid fossae, parapharyngeal space, posterior nasal cavity and maxillary sinus, retropharyngeal nodes, and levels II through V. If a patient has N+ disease, level IB should be covered. If sphenoid sinus is involved, the entire sphenoid sinus should be included. If clivus is involved the entire clivus should be included.

• CTV3 (low-risk volume) includes contralateral uninvolved nodal disease and includes nodal level V. Level IB of the contralateral neck may be optionally excluded.

• CTV3 also includes medial retropharyngeal nodes to the superior edge of the hyoid bone. The inferior margin extends to 2 cm above the sternoclavicular joint.

6.2. Clinical Target Volume Delineation

• CTV1 and CTV2 delineation in a patient with AJCC 2010 clinical stage T2N3a squamous cell carcinoma of the nasopharynx receiving definitive IMRT concurrent with chemotherapy is shown in Figure 6-10. For this patient, an MRI as well as positron emission tomography (PET) fusion was done, as shown in the figure.

Figures 6-11 through 6-14 illustrate CTV delineation for definitive IMRT for patients with nasopharyngeal cancer of the following stages: Figure 6-11, T2N2M0; Figure 6-12, T2N3a; Figure 6-13, T4N2; and Figure 6-14, T4N3a (all AJCC 2010).

6.3. Suggested Target and Normal Tissue Doses

• See Chapter 4 for suggested target and normal tissue doses.

6.4. Intensity-Modulated Radiation Therapy Results

• Xia et al. compared the treatment plans involving IMRT for nasopharyngeal carcinoma. In their series, coverage of the GTV as well as the CTV was superior with the inverse-planned IMRT plans. In addition, when using proper dose constraints to the normal structures, inverse-planned IMRT plans achieved the least dose delivered to the brain stem, chiasm, and optic structures, as well as to the parotid. There was substantial reduction of the mean parotid dose to as low as 21.4 Gy.56

FIGURE 6-10. CTV (clinical target volume) delineation using MRI and PET fusion in a patient with T2bN0M0 (AJCC 1997) nasopharyngeal carcinoma receiving definitive IMRT. (A) CT–MRI fusion. (B) CT–PET fusion. Here GTV is light blue, CTV1 is yellow, and CTV2 is red.

FIGURE 6-11. CTV (clinical target volume) delineation in a patient with a T2N2M0 (AJCC 2010) nasopharyngeal carcinoma receiving definitive IMRT. p, parotid gland.

FIGURE 6-12. CTV delineation in a patient with T2N3a (AJCC 2010) nasopharyngeal carcinoma receiving definitive IMRT. p, parotid gland.

FIGURE 6-13. CTV delineation in a patient with a T4N2 (AJCC 2010) nasopharyngeal carcinoma receiving definitive IMRT.

FIGURE 6-14. CTV delineation in a patient with a T4N3a (AJCC 2010) nasopharyngeal carcinoma receiving definitive IMRT.

• A classic paper by Lee et al. showed that in 87 patients treated with IMRT, the 4-year local progression-free survival, regional progression-free survival, distant metastasis recurrence-free survival, and overall survival rates were 94%, 98%, 66%, and 73%, respectively, with a median follow-up of 31 months.36 Excellent locoregional control of nasopharyngeal carcinoma was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.

• Kwong et al. presented the preliminary experience from Queen Mary Hospital in Hong Kong of 50 patients with T1-2N0-1M0 nasopharyngeal cancer who underwent IMRT. With a median time of 14 months after the completion of radiotherapy, the 2-year nasopharynx, neck, and distant failure-free survival rates were 100%, 94.1%, 94%, respectively.57

• Lee et al.58 reported on patients with recurrent disease including that of the neck (n = 21), nasopharynx (n = 21), paranasal sinus (n = 18), and oropharynx (n = 16). IMRT proved effective in improving 2-year locoregional progression-free survival compared to conventional RT (52% vs 20%).

• Wolden et al. reported the IMRT results from Memorial Sloan-Kettering with local control rates and regional control rates of 91% and 93%, respectively.39

• In RTOG 0225, a phase II feasibility study of IMRT with or without chemotherapy for nasopharyngeal carcinoma showed excellent outcomes in a multi-institutional setting, with 2-year local control rates of 93%.41

• Recent IMRT studies for nasopharyngeal cancer have looked into targeted agents with the goal of reducing distant metastasis. RTOG 0615 was a phase II trial adding bevacizumab to IMRT with standard concurrent chemotherapy. This study reported a 2-year distant metastasis-free survival rate of 91%.51 Similarly, Ma et al. added cetuximab to chemoradiation using IMRT showing distant metastasis-free survival rate of approximately 93%.50

• Two recent phase III studies from China investigated chemoradiation treatment for NPC patients. Chen et al.35 found that the addition of adjuvant cisplatin and fluorouracil chemotherapy did not provide significant improvement in failure-free survival after concurrent chemoradiotherapy in stage III–IV disease. However another group, Chen et al.,25 found survival benefits in stage II patients treated with concurrent chemoradiation compared with RT alone.

• Chao and associates previously presented results from Washington University’s Mallinckrodt Institute of Radiology (MIR).59 In their study 103 patients were treated with conventional external beam radiation therapy only (MIR-RT) and 22 patients received external beam irradiation with concomitant chemotherapy according to the Intergroup Study (IGS) 0099 regimen. Among the latter group, 13 patients were treated by conventional beam arrangement (MIR-CRT) and 9 patients were treated with IMRT (MIR-IMRT). Three-year progression-free survival for radiation therapy alone was 51% for MIR patients as compared with 24% for IGS (P < 0.05). Progression-free survival at 3 years after chemoradiotherapy was 90% for MIR patients and 69% for IGS (P < 0.05).

• In the above-mentioned study by the MIR group, G-tube was placed in two patients during the course of IMRT. No grade III–IV late complications were observed in patients treated with IMRT. Six grade II and four grade I late xerostomia occurrences were observed. Decreased hearing was common with cisplatin chemotherapy.

• Figure 6-15 shows pre- and post-IMRT MRI sections of a T4N3 nasopharyngeal carcinoma patient, showing complete regression of the tumor.

FIGURE 6-15. Pre-IMRT (A–E) and post-IMRT (F–J) MRI sections of a patient with T4N3 nasopharyngeal carcinoma showing complete regression of the tumor after a total IMRT dose of 70.3 Gy with concurrent platinum-based chemotherapy.

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