Chapter 27.

RECURRENT NASOPHARYNGEAL
CANCER CASE STUDY
WEI-YUAN MAI, MD, TAI-XIANG LU, MD, XIAO-WU DENG, PHD

Patient History support his head and neck. A planning CT scan was per-
formed in the treatment position on a Somatom Plus 4 CT
A 34-year-old male presented in February 1998 with a 1-
simulator (Siemens Medical Systems, Munich, Germany)
month history of right-sided tinnitus. Clinical examina-
with 3 mm slices. The anatomic extent of the scan was from
tion revealed bilateral palpable enlarged lymph nodes in
the upper neck (right 1.8 × 1.8 cm, left 1.5 × 1.5 cm).
the vertex of the head to below the clavicles. Intravenous
contrast was administered.
Endoscopic examination demonstrated a nasopharyngeal
lesion, and a biopsy was performed. The pathology was
consistent with a World Health Organization type III undif- Target and Tissue Delineation
ferentiated carcinoma. A computed tomography (CT) scan
Target volumes were delineated on each axial slice of the
revealed extension of the nasopharyngeal mass into the
planning CT scan. The gross tumor volume (GTV) in this
right parapharygneal space. The remainder of the workup
patient was defined as the gross extent of the tumor visu-
was negative for metastases. The tumor was thus staged as
alized on imaging (CT and MRI) studies. The clinical tar-
T2bN2M0.
get volume (CTV) was defined as the GTV plus a 1 cm
The patient was treated with conventional radiation
margin for potential microscopic spread, except in regions
therapy (RT). Total doses to the nasopharynx and the neck
adjacent to the brainstem and/or spinal cord, where the
lymph node were 70 and 60 Gy, respectively, delivered in
margin was reduced to 0.5 cm. A planning target vol-
2 Gy daily fractions. Chemotherapy was not administered.
ume (PTV) was generated by expanding the CTV by 0.5
The patient achieved a complete response based on clini-
to 1.5 cm. Adjacent to the brainstem and spinal cord, a
cal and follow-up CT examinations.
0.5 cm expansion was used. Figure 27.2-2 illustrates the
In December 2000, the patient presented with recurrent
GTV, margin 1, and margin 2 delineated in this patient.
right-sided tinnitus and progressive diplopia. Clinical exam-
ination demonstrated a nasopharyngeal mass and a right
cranial nerve VI deficit. A biopsy was performed, and the
pathology confirmed a local recurrence. Restaging CT and
magnetic resonance imaging (MRI) scans demonstrated a
nasopharyngeal mass involving the oropharynx and right
cavernous sinus with erosion of the skull base (foramen
lacerum, apex of the petrous temporal bone, clivus). A
metastatic workup, including chest radiography, liver ultra-
sonography, and liver function tests, was negative. His
Karnofsky Performance Score at the time of recurrence was
80. Salvage RT was performed using intensity-modulated
radiation therapy (IMRT).

Simulation
The patient was immobilized in the supine position using FIGURE 27.2-1. A thermoplastic face mask was used for immobiliza-
a thermoplastic face mask (Figure 27.2-1). A customized tion with a customized “pillow” to support the patient’s head and neck.
“pillow” made of molded polyurethane foam was used to (To view a color version of this image, please refer to the CD-ROM.)

604
 Recurrent Nasopharyngeal Cancer: Case Study / 605

FIGURE 27.2-2. Axial computed tomography slices illustrating the gross tumor volume (red), margin 1 (light red), and margin 2 (blue). Note that adja-
cent to the brainstem, a smaller expansion margin (0.5 cm) was used for both the CTV and the PTV. (A) Oropharynx; (B) nasopharynx; (C) skull base;
(D) cavernous sinus. (To view a color version of this image, please refer to the CD-ROM.)

Organs at risk (OAR) in this patient included the brain-
stem, spinal cord, optic nerves, optic chiasm, eyes, tem-
poral lobes, parotid glands, temporomandibular joints, and
mandible.
Treatment Planning
Inverse treatment planning was performed using the
CORVUS planning system, version 3.0 (North American
Scientific, NOMOS Radiation Oncology Division,
Cranberry Township, PA). The input parameters for IMRT
planning for the GTV, margin 1, and margin 2 in this patient
are summarized in Table 27.2-1. The total prescribed doses
for GTV, margin 1, and margin 2 were 70, 60, and 50 Gy,
respectively. Corresponding daily fractions were 2.3, 2.0,
and 1.7 Gy, respectively. Threshold doses to the OAR were
based on the publication of Emami and colleagues.1 In
general, we used more restricted dose limits because the
606 / Intensity-Modulated Radiation Therapy

TABLE 27.2-1. Input Parameters

Targets and Critical Structures Goal and Limit, Gy Minimum Dose, Gy Maximum Dose, Gy

GTV 70 68 74
Margin 1 60 56 64
Margin 2 50 48 54
Brainstem 30 10 46
Spinal cord 30 10 40
Optic chiasm 40 30 50
Optic nerves 40 30 50
Eye 15 10 20
Lens 3 1 5
Temporal lobe 30 10 40
Parotid gland 26 20 30
Temporomandibular joint 30 10 40
Mandible 30 20 40

GTV = gross tumor volume.

patient had undergone RT. The targets were given priori-
ty over normal structures in the planning process.
A treatment plan was generated, reviewed, and accept-
ed. Each axial image was evaluated for dosimetric cover-
age of the target volumes and avoidance of normal
structures. An optimized treatment plan is shown in Figure
27.2-3. Dose-volume histograms for the GTV, margin 1,
margin 2, and OAR are summarized in Table 27.2-2 and
Figure 27.2-4. The CTV is denoted as GTV plus margin 1,
and the PTV is denoted as CTV plus margin 2.
Treatment Delivery and Quality
Assurance
The treatment was delivered with a dynamic multileaf
intensity-modulating collimator using a segmental
tomotherapy technique (North American Scientific). The
gantry rotation arc was 105° to 255°, and beamlet patterns
changed every 5°. The patient was treated on a Varian Clinic
600C (Varian Medical Systems, Palo Alto, CA) using 6 MV
photons.
The treatment plan was verified using a film phantom.
Commercial prepackaged film (XV-2, Eastman Kodak Co.,
Rochester, NY) in a transverse orientation was used to con-
firm that the dose pattern was correct relative to the isocen-
ter of the linear accelerator. These films were qualitatively
compared for the shape and intensity with images gener-
ated by the computer.
Port films were taken for the first two fractions and week-
ly thereafter to verify isocenter placement. Six 1 cm treat-
ment arcs were used in this patient. Daily treatment delivery
time for the patient was approximately 20 minutes.
Clinical Outcome
The patient tolerated treatment well, without interruptions.
A follow-up clinical examination revealed the complete
response of the recurrent tumor. However, the cranial nerve
VI deficit did not resolve. At 3 months following completion
of IMRT, MRI demonstrated resolution of the nasopharyn-
geal lesion. However, persistent skull base destruction was
noted. MRI performed at 9 months revealed identical results.
When last seen (32 months post-treatment), the patient
remained clinically without evidence of disease recurrence.
His mucous membrane was slightly atrophic and dry. He
needed to sip liquids to swallow dry food and carry a water
bottle. However, there were no obvious RT-related side
effects to his eyes, spinal cord, or brain.
Our initial experience using IMRT in 49 patients with
recurrent nasopharyngeal carcinoma was recently present-
ed.2 The median dose to the nasopharynx in the initial con-
ventional RT treatment was 70 Gy (range 60.9–78 Gy). Using
our IMRT approach, a mean dose of 71.4 Gy was delivered
to the GTV. Three patients with positive nodes received adju-
vant chemotherapy (cisplatin, 5-fluorouracil) following
IMRT; the remainder were treated with IMRT alone.
At a median follow-up of 9 months (range 3–13
months), the locoregional control rate was 100%. Three
patients developed metastases at a distant site (two in bone,
one in the liver and lung). Overall, treatment was well tol-
erated. The percentages of patients with acute grade 2 skin
and mucosal toxicities were 2% and 43%, respectively.
Grade 3 mucosal toxicity was seen in 4% of patients.
Twenty-three patients (47%) experienced grade 2 xeros-
tomia (18 moderate, 5 severe). All patients are being fol-
lowed closely to assess late toxicity and treatment outcome.
 Recurrent Nasopharyngeal Cancer: Case Study / 607

FIGURE 27.2-3. Treatment plan and isodose distributions: 70 Gy (red), 65 Gy (pink), 60 Gy (gold), 55 Gy (yellow), and 50 Gy (green). (A) Oropharynx;
(B) nasopharynx; (C) skull base; (D) cavernous sinus. (To view a color version of this image, please refer to the CD-ROM.)
608 / Intensity-Modulated Radiation Therapy

TABLE 27.2-2. Target and Normal Tissue Doses

Mean Minimum Maximum
Critical Volume, Dose, Dose, Dose,
Structures cm3 Gy Gy Gy

GTV 38.1 70.1 63.5 74.3

Margin 1 55.6 65.4 50.9 73.1
Margin 2 89.5 57.5 36.8 72.4
Brainstem 31.3 32.1 11.1 63.5
Spinal cord 3.0 24.9 9.7 36.4
Optic chiasm 0.5 41.4 29.3 49.0
Optic nerve
L 0.8 31.2 14.9 47.9
R 0.6 32.7 14.5 56.4
Eye
L 9.8 9.3 1.5 24.1
R 9.9 10.8 1.9 28.2
Lens
L 0.2 3.0 1.9 5.2
R 0.2 3.2 2.2 5.6
Temporal lobe
L 34.5 24.5 3.3 59.7
R 27.3 28.4 3.7 67.9
Parotid gland
L 8.5 20.0 6.3 37.1 FIGURE 27.2-4. Dose-volume histograms of the target and normal tis-
R 9.2 25.0 9.3 50.1 sues. M1 = margin 1; M2 = margin 2; OC = optic chiasm; BS = brainstem;
Temporomandibular joint LP = left parotid gland; RP = right parotid gland; SC = spinal cord;
L 3.1 25.7 17.1 41.2
GTV = gross tumor volume.
R 3.7 29.9 20.8 52.3
Mandible
L 37.0 19.1 0.7 42.7
R 37.0 23.6 0.7 58.3

GTV = gross tumor volume, R = right, L = left.

Acknowledgments
We thank Bin S. Teh, MD, and E. Brian Butler, MD (Baylor
College of Medicine, Houston, TX), for their assistance
and recommendations regarding the planning and treat-
ment of this patient.
References
1. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue
to therapeutic irradiation. Int J Radiat Oncol Biol Phys
1991;21:109–22.
2. Lu TX, Mai WY, Teh BS, et al. Initial experience using intensity-
modulated radiotherapy for recurrent nasopharyngeal
carcinoma. Int J Radiat Oncol Biol Phys 2004;58:682–7.