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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4505_Библиотеки_им_академика_М_И_Перельмана
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Part 2 Site-Specifi c Indications and Techniques
C
E
Figure 7.5C-F
D
F
Chapter 7 Nasopharynx
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G
I
Figure 7.5G-J
H
J
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Part 2 Site-Specifi c Indications and Techniques
Case
Study
7-6
tumor showed nonkeratinizing poorly di erentiated squamous cell carcinoma.
A lateral view of the PET scan (Fig. 7.6A) shows the
primary tumor and extensive adenopathy including level
V nodes, and an axial image of PET-CT scan (Fig. 7.6B)
demonstrates the extent of the adenopathy in the posterior neck. Not shown are bilateral retropharyngeal and
contralateral neck nodes. An MRI was also performed and
demonstrated erosion of the clivus. Given the extent of the
disease with skull base involvement, she was dispositioned
for induction cisplatin and docetaxel, which caused renal
function impairment a er one cycle. erefore, cisplatin was replaced by carboplatin for two additional cycles.
Chemotherapy yielded a complete response of the primary
A 50-year-old woman presented with a le
upper neck mass and decreased hearing.
Examination revealed multiple nodes in the
le neck including level V region and a tumor
in the nasopharynx. Biopsy of the primary
tumor and partial response of the neck nodes. She was then
treated with IMRT and concurrent carboplatin.
Prechemotherapy gross disease in the nasopharynx
and neck with margin were outlined as CTV
and CTV
was placed above the thyroid notch, and the low neck was
treated with parallel opposed anterior and posterior portals. A larynx block was used for the rst 40 Gy, and then
a full midline block was added for 10 Gy. e elds were
reduced o level IV and 10 Gy was given to level III nodes
bilaterally, and then an additional 10 Gy was administered
to the right mid neck. Isodose distributions on axial images
of the treatment plan are shown (Fig. 7.6C–G). Views of
the roof of the nasopharynx (Fig. 7.6C), midnasopharynx (Fig. 7.6D), retropharyngeal region anterior to C1
(Fig. 7.6E), and upper (Fig. 7.6F), and mid neck (Fig. 7.6G)
are shown. e residual posterior node can be seen in
Figure 7.6F and G, black arrow. e patient remains with-
out disease 2 years from therapy.
(60 Gy) added additional margins. Isocenter
ID
(70 Gy)
HD
Figure 7.6A,B
BA
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C
D
FE
G
Figure 7.6C-G
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demonstrate the full thickness destruction of the clivus (note the absence of bone). e isodose distribution
A 40-year-old man was diagnosed with poorly
di erentiated carcinoma of the nasopharynx,
stage T3, N2, M0. He received concurrent
radiation and chemotherapy.
e sagittal and axial images (Fig. 7.7A,B)
demonstrates the ability of IMRT to provide conformal
coverage in this di cult case. e tumor extent necessitated taking the surface of the brain stem to 60 Gy to yield
reasonable tumor coverage. e patient was without disease at the follow-up visit 3 years out from therapy without
neurologic de cit.
AB
Figure 7.7A,B
Case
Study
7-8
and roof. A biopsy was positive for undi erentiated NPC,
WHO type 3. MRI revealed a large, le -sided nasopharyngeal tumor with destruction of the ipsilateral clivus, oor
of the sella, and oor of the medial portion of middle fossa,
with tumor extending into the adjacent sphenoid sinus.
ere was minimal asymmetrical plaquelike thickening
along the le parasellar dura suggesting intracranial tumor
invasion. e le petrous apex was irregularly eroded. e
tumor in ltrated the le prevertebral muscle and was associated with large le lateral retropharyngeal lymphadenopathy. e clinically apparent 4-cm lymph node in the upper
A 30-year-old Asian man presented with a
le neck mass and headaches. Examination
revealed a 4-cm le neck node and a nasopharyngeal mass that involved the le torus
tubarius, fossa of Rosenmüller, posterior wall,
jugular region was seen along with multiple additional nodes
suspicious for metastatic lymphadenopathy. Stage: T4, N1,
M0. e treatment consisted of a combination of concurrent cisplatin and radiation. IMRT with nine separate beam
angles was delivered with “step and shoot” collimation.
A separate isocentrically matched anterior eld treated the
low neck and supraclavicular fossa to 50 Gy.
Figure 7.8 shows isodoses on a coronal (Fig. 7.8A)
and axial (Fig. 7.8B) image through the primary tumor
and neck. e primary nasopharynx tumor and involved
neck nodes received 70 Gy, and subclinical disease in the
contralateral neck received 57 Gy. e brain stem and optic
chiasm doses were limited to 54 Gy and the spinal cord to
45 Gy. He is without disease 9 years out from treatment
with only grade-1 xerostomia.
Chapter 7 Nasopharynx
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AB
109
Figure 7.8A,B
Case
Study
7-9
of the right palate.
A biopsy of the primary tumor was positive for moderately di erentiated squamous cell carcinoma. An axial MRI
image (Fig. 7.9A) demonstrates tumor extension adjacent
to Meckel’s cave, and a coronal image (Fig. 7.9B) demonstrates the bulky disease with extension through the middle
cranial fossa. He was staged T4, N1, M0 and treated with
IMRT and three cycles of high-dose cisplatin.
A 47-year-old man presented with epistaxis
and hearing loss for nearly a year. Examination
revealed right neck adenopathy and a tumor
lling the nasopharynx. He also had atrophy
of the right tongue and diminished elevation
CTVHD (70 Gy) and CTVID (60 Gy) were delineated,
isocenter was placed above the thyroid notch, and the low
neck was treated with an anterior beam. A larynx block was
used for the rst 40 Gy; then a full midline block was added
for 10 Gy. Figure 7.9C-E shows axial (Fig. 7.9C), sagittal
(Fig. 7.9D), and coronal (Fig. 7.9E) isodose distributions
through the nasopharynx. e blue arrows (italics) show
the disease along the middle cranial fossa oor. An axial
isodose (Fig. 7.9F) at the level of intracranial extension
is also shown. He was restaged and found to have a partial response. He received adjuvant chemotherapy, which
was poorly tolerated, and died due to complications from
therapy.
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A
C
B
D
E
Figure 7.9A-F
F
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imaging (MRI) is generally better for delineating the disease
extent, particularly at the skull base region, it is crucial to
incorporate diagnostic MRI ndings into the planning process, preferably by fusion.
Gross Target Volume
GTV represents all areas determined from clinical examination and imaging studies to contain macroscopic disease.
Any cervical lymph node >1 cm or retropharyngeal lymph
node >0.5 cm is considered to contain a tumor.
Clinical Target Volume
Two CTVs are generally delineated.
• CTVHD or CTV1 delineates volumes to receive the highest
dose, usually 70 Gy, which includes the primary tumor and
involved nodes with 0.5- to 1.0-cm margins. Protection of
neural structures may necessitate tighter margins on the
GTV. e entire nasopharynx is encompassed unless the
tumor is well lateralized.
• CTVID or CTV2 delineates volumes to receive an interme-
diate dose, usually around 60 Gy. e general guidelines
for delineating CTVID to provide additional margin on the
primary tumor are as follows:
Anterior: posterior third of the nasal cavity and maxil-
°
lary sinuses, or 1 cm beyond CTVHD if these structures
are encompassed by CTVHD.
Posterior: retropharyngeal regions and clivus.
°
Lateral: parapharyngeal regions extending to the middle
°
of the pterygoid muscles or more laterally as dictated by
the extent of the tumor.
Superior: inferior half of the sphenoid sinus, and adja-
°
cent skull base, or 1 cm superior to CTVHD for T3 to T4
tumors.
Inferior: 1-cm margin beyond the nasopharynx or infe-
°
rior to CTVHD.
Elective Nodal Irradiation
In the absence of clinical nodal involvement, levels II to
V receive elective irradiation. ese levels are generally
included in CTV
as radiation is given in 33 to 35 frac-
ID
tions over 6.5 to 7 weeks. In the presence of involved nodes,
CTVID includes levels IB to V outside CTVHD. In situations
where IMRT is used only for the primary tumor and upper
neck nodes, the lower neck lymphatics are irradiated with
a matching anterior portal. However, an apposed posterior
beam is o en required to achieve adequate dosing to positive
posterior cervical, level V nodes.
Background Data
Table 7.1
Stage (1992 AJCC
System)
T1 55 87
T2 138 75
T3 67 63
T4 118 45
Total 378 66
Ajcc, American Joint Committee on Cancer.
Data from M.D. Anderson Cancer Center.
Adapted from Sanguineti G, Geara FB, Garden AS, et al. Carcinoma of
the nasopharynx treated by radiotherapy alone: determinants of local
and regional control. Int J Radiat Oncol Biol Phys 1997;37:985–996, with
permission.
Table 7.2
Stage (1992
AJCC System)
N0 80 95
N1 32 94
N2a 38 91
N2b 50 80
N2c 80 77
N3 70 71
AJCC, American Joint Committee on Cancer.
Data from M.D. Anderson Cancer Center.
Adapted from Sanguineti G, Geara FB, Garden AS, et al. Carcinoma of
the nasopharynx treated by radiotherapy alone: determinants of local
and regional control. Int J Radiat Oncol Biol Phys 1997;37:985–996, with
permission.
Failures at the Primary Site in Tumors of
the Nasopharynx
No. of
Patients
Nodal Recurrence By Lymph Node Stage
and Histology
No. of
Patients
10-yr Actuarial
Local Control (%)
10-yr Actuarial
Regional Control (%)
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Table 7.3
Review on Squamous Cell Carcinoma of the Nasopharynx: Survival and Cumulative Incidence (%) of
Persistence and Relapse
Author
No. of
Cases
Persistence Relapse Survival
L R M L R M 5 yr 10 yr
Baker 99 — — — 32 34 38 24 —
Cellai et al. 138 20 18 — 17 12 18 40 —
Hagbhin et al. 79 — — — 25 4 24 33 19
Hoppe et al. 82 — — — 21 9 18 62 55
Mesic et al. 251 — — — 20 13 29 52 —
Moench and Phillips 146 — — — 38 14 22 38 —
Rahima et al. 91 — — — 35 30 35 62 42
Sham and Choy 759 — — — 18 21 24 — —
Stein et al. 49 — — — 22 8 14 42 —
Vikram et al. 107 — — — 31 4 17 56 —
Yamashita et al. 77 — — — 58 39 16 25 —
Lee et al. 5,037 13 13 6 18 17 30 52 42
L, local; R, regional; M, distant metastases.
From Lee AWM, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985. Overall survival and
patterns of failure. Int J Radiat Oncol Biol Phys 1992;23:261, with permission.
Table 7.4
Results of Adjuvant and Neoadjuvant Chemotherapy and Radiation: Randomized Trialsa (Literature Review)
No. of Patients
First Author Chemotherapy: No. of Cycles Radiation (Gy)
Randomized Survival
Rossi VCA: ×6 after RT 60–70 229 RT: 67%
RTC: 59% (4Y-A)
Chan CF: ×2 before, ×4 after RT 66 82 RT: 81%
RTC: 80% (2Y-A)
Chua CE: ×2–3 before RT 66–74 334 RT: 71%
RTC: 78% (3Y-A)
INCSG BEC: ×3 before RT 65–70 339 RT: 45%
RTC: 67% (Crude-DFS)
Ma CBF: ×2–3 before RT 68–72 456 RT: 56%
RTC: 63% (5Y-A)
a
All trials randomized patients to radiation alone or radiation and chemotherapy.
INCSG, International Nasopharynx Cancer Study Group; VCA, vincristine, cyclophosphamide, adriamycin; CF, cisplatin, 5-FU; CE, cisplatin, epirubicin; BEC,
bleomycin, epirubicin, cisplatin; CBF, cisplatin, bleomycin, 5-FU; C, cisplatin; RT, radiation alone; RTC, radiation and chemotherapy; Y-A, year actuarial; DFS,
disease-free survival.
Data from Rossi A, Molinari R, Boracchi P, et al. Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in localregional nasopharyngeal cancer: results of a 4-yr multicenter randomized study. J Clin Oncol 1988;6:1401–1410; Chan AT, Teo PM, Leung TW, et al. A
prospective randomized study of chemotherapy adjunctive to defi nitive radiotherapy in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys
1995;33:569–577; Chua DT, Sham JS, Choy D, et al. Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing
cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal
carcinoma: Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Cancer 1998;83:2270–2283; INCSG. Preliminary results of
a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV (N2, M0)
undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. Int J Radiat Oncol Biol Phys 1996;35:463–469; and Ma J, Mai HQ,
Hong MH, et al. Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with
locoregionally advanced nasopharyngeal carcinoma. J Clin Oncol 2000;19:1350–1357.
Chapter 7 Nasopharynx
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Table 7.5
Results of IMRT in the Treatment of Nasopharyngeal Carcinoma (Literature Review)
Authors Patient No. Median Follow-Up % Local Control % Nodal Control
Lee et al. 67 31 mo 97% (4 yr) 98
Kam et al. 63 29 mo 92% (3 yr) 98
Kwong et al. 33 24 mo 100% (3 yr) 100
Wolden et al. 74 35 mo 91% (3 yr) 93
Tham et al. 195 37 mo 90% (3 yr) ND
Lee et al. 68 2.6 yr 93% (2 yr) 91
Lin et al. 370 31 mo 95% (3 yr) 97
Han et al. 305 35 mo 94% (3 yr) 98
Ng et al. 193 31 mo 95% (2 yr) 96
IMRT, intensity-modulated radiation therapy; ND, not described.
Data from Lee N, Xia P, Quivey JM, et al. Intensity-modulated radiation therapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF
experience. Int J Radiat Oncol Biol Phys 2002;53:12–22; Kam MK, Teo PM, Chau RM, et al. Treatment of nasopharyngeal carcinoma with intensitymodulated radiation therapy: the Hong Kong experience. Int J Radiat Oncol Biol Phys 2004;60:1440–1450; Kwong DL, Pow EH, Sham JS, et al. Intensitymodulated radiation therapy for early-stage nasopharyngeal carcinoma: a prospective study on disease control and preservation of salivary function. Cancer
2004;101:1584–1593; Wolden SL, Chen WC, Pfi ster DG, et al. Intensity-modulated radiation therapy (IMRT) for nasopharynx cancer: update of the Memorial
Sloan-Kettering experience. Int J Radiat Oncol Biol Phys 2006;64:57–62; Tham IW, Hee SW, Yeo RM, et al. Treatment of nasopharyngeal carcinoma using
intensity-modulated radiotherapy-the National Cancer Centre Singapore experience. Int J Radiat Oncol Biol Phys 2009;75:1481–1486; Lee N, Harris J, Garden
AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial
0225. J Clin Oncol 2009;27:3684–3690; Lin S, Lu JJ, Han L, et al. Sequential chemotherapy and intensity-modulated radiation therapy in the management of
locoregionally advanced nasopharyngeal carcinoma: experience of 370 consecutive cases. BMC Cancer 2010;10:39; Han L, Lin SJ, Pan JJ, Chen CB et al.
Prognostic factors of 305 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy. Chin J Cancer 2010;29:145–150; and Ng WT, Lee
MC, Hung WM, et al. Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol
Phys 2010; Epub.
Table 7.6
First Author, Year Pt Number Concurrent Approach
Randomized Trials of Concurrent Chemotherapy and Radiation for Nasopharyngeal Cancer
Adjuvant
Chemotherapy
Survival (Experimental
vs. Control)
Al-Sarraf et al., 1998 147 CDDP wk 1, 4, and 7 Yes 78% vs. 47% (p = 0.05)
Lin et al., 2003 284 CDDP and 5-FU wk 1 and 5 No 72% vs. 53% (p = 0.002)
Chan et al., 2005 350 CDDP every week No 70% vs. 59% (p = 0.065)
Zhang et al., 2005 115 Oxaliplatin every week No 96% vs. 83% (p = 0.02)
Wee et al., 2005 221 CDDP wk 1, 4, and 7 Yes 80% vs. 65% (p = 0.006)
Lee et al., 2005 354 CDDP wk 1, 4, and 7 Yes 78% vs. 78% (p = 0.97)
CDDP, cisplatin; 5-FU, 5-fl uorouracil.
Data from Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III
randomized intergroup study 0099. J Clin Oncol 1998;16:1310–1317; Lin J, Jan J, Hsu C, et al. Phase III study of concurrent chemoradiotherapy versus
radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect onoverall and progression-free survival. J Clin Oncol 2003;21:631–637; Chan AT,
Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal
carcinoma. J Natl Cancer Inst 2005;97:536–539; Zhang L, Zhao C, Peng P, et al. Phase III study comparing standard radiotherapy with or without weekly
oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 2005;23:8461–8468; Wee J, Tan EH, Tai BC,
et al. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee
on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol 2005;23:6730–6738; and Lee AW,
Lau WH, Tung SY, et al. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal
carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol 2005;23:6966–6975.
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