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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Larynx Cancer
111
that 2.25 Gy is more effective than 2 Gy per day for these lesions (i.e., 63 Gy at 2.25 Gy per
fraction for 28 fractions). T2 lesions of the glottic larynx can be treated to a total dose of 70
Gy at 2 Gy per day (in 35 daily fractions over 7 weeks).
For patients whom bilateral nodal irradiation is indicated, conventional radiotherapy
using parallel-opposed fields is often associated with xerostomia. This adverse effect occurs
even when treatment is limited to an elective dose of 46–50 Gy. Xerostomia is resulted of
irradiation of substantial parts of both the parotid and submandibular salivary glands, located
in close proximity to level II neck nodes. IMRT allows unilateral and, in some cases (N0
patients where the superior limit of level II nodes for the electively irradiated neck is set at the
inferior aspect of the transverse process of C1), bilateral parotid gland sparing. The posterior
border of the submandibular gland represents the anterior boundary of level II neck nodes,
making them difficult to spare even with IMRT.
Partial organ radiation of early tumors is possible with IMRT. However, organ motion on
swallowing and the steep dose gradients created with IMRT in a small volume would make
geographical miss a real possibility and, therefore, it is not advised at present. For us, any
reduction in the PTV should be done in the context of clinical studies. Thus, we suggest the
inclusion of the entire larynx, including the thyroid cartilage, in the primary CTV. Other
authors, however, have suggested the inclusion of only the ipsilateral hemi-hypopharynx and
hemi-larynx in piriform fossa and lateral pharyngeal wall tumors.
For locally advanced tumours, at our institution, the entire larynx/hypopharynx complex
is included within the radical CTV, from the tip of the epiglottis to the cricoid cartilage or 2
cm above or below the superior and inferior extent of the tumor; whichever is larger (figure –
6).
Figure 6. Isodose lines distribution of IMRT planning for locally advanced laryngeal cancer.
For standard fractionation a total dose of 70 Gy at 2 Gy per daily fraction (in 35 fractions
over 7 weeks) to gross disease is indicated. The prescribed dose to subclinical disease is 4450 Gy at 2 Gy per daily fraction. For concomitant boost radiotherapy therapy a total dose of
72.0 Gy is given in 42 fractions over 6 weeks as 32.4 Gy in 18 fractions in 3 weeks (1.8
Gy/fraction/day) to a large field including subclinical disease followed by another 21.6 Gy in
12 fractions (1.8 Gy/fraction) to the same field, and a second daily fraction at least 6 h later
consisting of 18.0 Gy in 12 fractions (1.5 Gy/fraction) to a small “boost field”. For adjuvant
irradiation a Standard fractionation is recommended with a total dose of 60– 66 Gy at 2 Gy
Gustavo Arruda Viani
112
Organ at risk
Decription
Spinal cord
Maximum dose ≤ 45–50 Gy.
Brainstem
Dose ≤ 54 Gy.
Parotid glands
50% of the volume of each parotid receiving ≤ 20 Gy (if possible) and mean dose
< 26 Gy.
Mandible
Mandible maximum dose ≤ 70 Gy.
Brachial plexus
Brachial plexus dose <60 Gy.
Tracheostomas
Tracheostomas are limited to ≤ 50 Gy unless in tumors with significant subglottic
extension, or emergent tracheostomy, or tumors with extranodal extension in neck
level VI, or with close/+ margin, in which case it is boosted to 60–66 Gy.
Larynx
For other head and neck primary sites, the goal mean dose to the larynx should be
kept below 50 Gy for 2/3 of organ.
But, 70 Gy carries 5% risk of laryngeal cartilage necrosis.
per fraction (in 30–33 fractions over 6–6. weeks), as used in the RTOG randomized trial.
Cisplatin-based chemotherapy (100 mg/m2 IV on days 1, 22, 43) or cisplatin 30 mg/m2 IV
weekly with concurrent radiation therapy is the regimen best supported by the available
literature.
The organs at risk are the spinal cord, brain stem, parotid glands, submandibular glands,
mandible, and esophagus. A margin is added to spinal cord and brain stem to obtain a PRV
according to ICRU 62. Dose-limitation guidelines in radiation therapy of hypopharyngeal
malignancies are described in table-9.
Table 9. Limit doses for organ at risks
Conclusion
• In the last decades the treatment of laryngeal cancer has substantially involved. At
the beginning of the century, the most part of patients were treated by surgery, and
now, chemoradiation has been the treatment choice for locally advanced disease.
• Total and partial laryngectomy surgeries were and still are the mainstream surgical
procedures to treat malignant tumors of the larynx.
• In the early 1990s, the organ preservation treatments using concurrent chemo-
radiation therapy were introduced, and a paradigm change in treatment was
experienced.
• Chemoradiation treatment have demonstrated survival rates similar to total
laryngectomy , while preserving the larynx of the patients.
• In addition, new developments in molecular tumor biology are opening a new era in
the treatment of malignant tumor of the larynx.
Nasopharyngeal Cancer
Uncommon in most countries (Highest incidences in China, SE Asia &
Eskimos) with a peak incidence in 4 - 5th decades of life.
In US 7/1,000,000,000 people will get NPC with 2600 cases in 2010, being 2X
more common in males over females .
Almost all NPC patients have evidence of exposure to the virus – connection not
completely understood. if a family member has NPC increase risk for relatives
(possible that shared diet or environmental exposure).
Symptoms from nasopharyngeal cancer are normally seen later in the course of
disease. The symptoms associated with nasopharynx tumors include:
Nasal stuffiness, discharge, or epistaxis which occurs from tumor growth in the
posterior nasal fossa.The nasopharynx lesions cause unilateral serous otitis
media or nasal obstruction or epistaxis.Headache, pain in the occipital or
temporal area. Cervical lymph node involvement (seen in physical examination
60%-87% of the time).
An intake of the patient's thorough medical history must be performed as well as
a physical examination.The physical exam is done to assess the primary tumor
extent, palpate the neck node(s),test the cranial nerve(s) for assessment of
vision, and inspect the tympanic membranes for hearing functions. While
palpating the neck node(s) the following must be recorded: the size, laterality
and lowest extent of enlarged node.
Examinations include nasopharyngoscopy and biopsies of the nasopharynx and
adjacent suspicious areas. A Panendoscopy may or may not be done as well.
Radiographic studies of the head and neck are used to assess the locoregional
extent. MRI is the study of choice because of it's superior sensitivity. CT with
contrast is an acceptable substitute.
The treatment is guided by clinical staging. Patients with T1N0M0 disease are
better treated with radiation therapy alone (IMRT preferred) than
chemoradiation. All other clinical stages should be treated with the combination
between radiotherapy and chemotherapy.
Chapter 8
Abstract
Gustavo Arruda Viani
114
Introduction
Nasopharygeal cancer is a relatively uncommon disease in Western countries. However,
it is the most commonly diagnosed head and neck malignancy in Southeast Asia. The
majority of diagnosed nasopharyngeal cancers are of epithelial origin. In Southeast Asia the
nonkeratinizing poorly or undifferentiated squamous cell carcinoma [i.e., World Health
Organization (WHO) type II and III diseases] are the more commonly diagnosed being
responsible by up to 95% of all cases. On the other hand, in North America, 75% of cases are
WHO type I. Radiation therapy with or without chemotherapy association remains as the
primary treatment for nasopharyngeal cancer. As nasopharyngeal cancer tends to present with
regional lymphnodal metastasis, and is sensitive to both chemotherapy and radiation therapy,
multidisciplinary management is usually required for locally advanced disease.
1. Epidemiology
• In the Western hemisphere nasopharyngeal carcinoma (NPC) is rare with an annual
incidence of around 0.5/100,000, accounting for 2% of all head and neck cancers.
• On the other hand, in southern China and Hong Kong the disease is endemic with
annual incidence rates of up to 20–30/100,000.
• This disparity is related to histopathological subtypes. In North American series
keratinizing SCCs account for up to 68% of cases while in the Far East over 95% are
WHO type 2–3. The incidence of WHO type II and III is also high in Eskimo and
Native Alaskan populations and moderately increased in Malaysia, north Africa and
southern Europe.
• Age of diagnosis shows a bimodal distribution that peaks at 50–60 years of age, with
a small peak among adolescents in the low- to medium-incidence area, with a
male:female ratio of NPC is 2–3:1.
References
Parkin D, Muir C, Whelan S, et al: Cancer incidence in five continents. Lyon, France, IARC
Scientific Publications, 1992.
Lanier A, Bender T, Talbot M, et al: Nasopharyngeal carcinoma in Alaskan Eskimos Indians,
and Aleuts: a review of cases and study of Epstein-Barr virus, HLA, and environmental
risk factors. Cancer 1980; 46:2100-2106.
2. Risk Factors
A number of risk factors have been associated with nasopharyngeal cancers (Table 1).
Nasopharyngeal Cancer
115
Asiatic patients
Incidence higher in Asians, particularly those from southern China, Eskimos, and
Icelanders. This risk prevails in first generation immigrants to other parts of the
world.
Epstein –Barr
virus
Nonkeratinizing nasopharyngeal carcinomas are uniformly associated with Epstein-
Barr virus (EBV).
Patients usually have increased levels of immunoglobulin A antibody to the viral
capsid antigen and early antigen.
Monitoring EBV DNA in the serum of affected patients using real-time polymerase
chain reaction technology appears to be useful tool for gauging responses to therapy.
Familiary
history
Incidence in 1st-degree relatives is 4- to 10-fold that of the control population
Food
High consumption of salted fish and pickled food was suggested as a risk factor in
southern China and Hong Kong
Alcohol and
smoking
The association between smoking and alcohol consumption and NPC is
controversial; smoking may increases NPC by 2- to 6-fold
Table 1. Risk factors associated with nasopharyngeal cancer
References
Tai TM: Analytical epidemiology: risk factors for nasopharyngeal carcinoma. Curr Opin
Oncol 2001; 8:156.
Tai TM: Descriptive epidemiology of nasopharyngeal cancer. Curr Opin Oncol 2001; 8:114.
Parkin D, Muir C, Whelan S, et al: Cancer incidence in five continents. Lyon, France, IARC
Scientific Publications, 1992.
Lanier A, Bender T, Talbot M, et al: Nasopharyngeal carcinoma in Alaskan Eskimos Indians,
and Aleuts: a review of cases and study of Epstein-Barr virus, HLA, and environmental
risk factors. Cancer 1980; 46:2100-2106.
Liebowitz D: Nasopharyngeal carcinoma: the Epstein-Barr virus association. Semin Oncol
1994; 21:376-381.
Lo YM: Quantitative analysis of Epstein-Barr virus DNA in plasma and serum: applications
to tumor detection and monitoring. Ann N Y Acad Sci 2001; 945:68-72.
3. Anatomy
The nasopharynx lies beneath the skull base, posterior to and continuous with the nasal
cavities (Figure-1). It is lined in part by pseudostratified columnar respiratory-type epithelium
and also in part by non-keratinizing stratified squamous epithelium.
4. Clinical Features
• The most common presenting complaint is a painless upper neck mass with ~ 43% of
patients present with unilateral or bilateral cervical mass on examination.
• Nasal obstruction, epistaxis, and otitis media may be observed. Sore throat occurs in
about 15% of patients and is related to spread into the oropharyngeal wall. About
Gustavo Arruda Viani
116
30% patients present with blood-stained nasal discharge, uni- or bilateral nasal
obstruction (which may induce a nasal twang), or posterior nasal discharge
• Headache in NPC is usually unilateral and temporoparietal in location, and usually
indicates skull base involvement with disease. Facial pain may be referred from any
of the three divisions of the trigeminal nerve. Occipital or temporal headache
frequently is seen. Proptosis occurs with posterior orbital invasion and displaces the
eyeball anteriorly. Trismus is related to the invasion of the pterygoid region.
• Neurologic symptoms and signs occur in about 25% of patients. Involvement of
cranial nerves II to VI indicates extension into the cavernous sinus. Cranial nerves IX
to XII and the sympathetic chain are involved in the lateral pharyngeal space.
• Petrosphenoidal syndrome of Jacod (unilateral trigeminal type neuralgia, unilateral
ptosis, complete ophthalmoplegia, and amaurosis) results from CN II–VI by direct
intracranial extension of NPC.
• Villaret’s syndrome (difficulty in swallowing; perversion of taste; problem in
salivation; paralysis and atrophy of the trapezius and SCM muscle; unilateral
weakness and atrophy of the soft palate or tongue; and hyperesthesia, hypoesthesia,
or anesthesia of the mucous membranes of the soft palate, pharynx, and larynx).
• Horner’s syndrome usually presents in conjunction with deficits of CN IX–XII
when cervical sympathetic nerves are also involved.
Figure 1. The nasopharynx. A Nasopharynx anatomy. B Nasopharynx on CT.
References
Skinner DW, Van Hasselt CA: Nasopharyngeal carcinoma: methods of presentation. Ear
Nose Throat J 1990; 69:237-240.
Lindberg R: Distribution of cervical lymph node metastases from squamous cell carcinoma of
the upper respiratory and digestive tracts. Cancer 1972; 29:1446-1449.
Nasopharyngeal Cancer
117
Benign tumours
Juvenile angiofibroma
Malignant tumours
Nasopharyngeal carcinoma (NPC) 85%*
WHO type 1—keratinizing squamous cell carcinoma
WHO type 2—non-keratinizing (differentiated) carcinoma
WHO type 3—undifferentiated carcinoma
Non-Hodgkin’s lymphoma
(Hodgkin’s lymphoma rare) 10%
Adenoid cystic carcinoma
Adenocarcinoma and minor salivary gland tumours
Plasmacytoma
Melanoma
Sarcoma (especially rhabdomyosarcoma)
Chordoma
5. Pathology
The WHO classification is the most widely used histopathological classification system
(Table-2). This system essentially differentiates between tumors that do or do not produce
keratin. Although the WHO classification is practical and simple, it does not give detailed
information on the cell type and degree of anaplasia. Therefore, this system is considered
inadequate to determine prognosis in regions where nasopharyngeal cancer is endemic.
Table 2. Pathological classification for nasopharyngeal tumors
References
International histological classification of tumors: Histological typing of upper respiratory
tract tumors, World Health Organization, 1991.
Marks JE, Phillips JL, Menck HR: The National Cancer Data Base report on the relationship
of race and national origin to the histology of nasopharyngeal carcinoma. Cancer
1998; 83:582-588.
6. Diagnostic and Evaluation
Diagnosis and evaluation of nasopharyngeal cancer initiates with a complete history and
physical examination. Table-3 summarizes the laborial tests and imaging studies to diagnosis
and to evaluate the nasopharyngeal cancers.
Gustavo Arruda Viani
118
History and
phisical
examination
The most common presenting symptom is a neck mass, while cervical lymph
adenopathy occurs in nearly 90% of patients, and 50% of cases present with bilateral
involvement.
Direct fiberoptic endoscopy of the nasopharynx, oropharynx, and hypopharynx is
required to evaluate the extent of the disease (figure-2)
Laboratory
Tests
Initial lab tests should include a complete blood count, basic blood chemistry, liver
function tests, and renal function tests.
EBV-specific serologic tests, which are usually positive in WHO type II and III
nasopharyngeal cancers, are also recommended.
Imaging
Studies
Imaging studies with MRI and/or CT of the head and neck areas are mandatory to
evaluate the extent of disease at the primary site.
MRI is preferred over CT as it is more sensitive for detecting soft tissue extension
(such as parapharyngeal space) and bone involvement. The sensitivity and specificity
of MRI for detecting locoregional extension has been repeatedly demonstrated in
both prospective and retrospective studies.
Chest X-ray is indicated to rule out pulmonary metastasis, while CT with IV contrast
of the thorax is required if the chest X-ray is equivocal.
The incidence of distant metastases is associated with the extent of regional lymph
node involvement. Results from a prospective trial revealed that the yield of bone
scan, liver ultrasound, and chest X-ray combined was 0%, 1.8%, 4.8%, and 14.3% for
N0, N1, N2, and N3 disease, respectively.
FDG-PET is valuable for detecting local and regional disease as well as distant
metastasis, and can be considered for initial evaluation and staging (figure-3)
Table 3. Evaluation for patients with nasopharyngeal cancer
Figure 2. Endoscopic view of an exophytic nasopharyngeal carcinoma (T), endoscope inserted through
the right nasal cavity. (B) Contrast-enhanced CT scan showing invasion of the left lateral wall of the
oropharynx by UCNT (T). Note the enlarged lymph nodes (N).
Figure 3. CT and PET-CT from a nasopharynx cancer with multiple nodes in both exams.
Nasopharyngeal Cancer
119
Tumor
T1 Tumor confined to the nasopharynx
T2 Tumor extends to soft tissues
T2a Tumor extends to the oropharynx and/or nasal cavity without parapharyngeal extensiona
T2b Any tumor with parapharyngeal extensiona
T3 Tumor involves bony structures and/or paranasal sinuses
T4 Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx,
orbit, or
masticator space
Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossab
N2 Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
N3 Metastasis in a lymph node(s)b more than 6cm and/or to supraclavicular fossa
N3a Greater than 6 cm in dimension
N3b Extension to the supraclavicular fossa
Distant metastases
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
References
Neel 3rd HB: Nasopharyngeal carcinoma: diagnosis, staging, and management. Oncology
(Williston Park) 1992; 6:87-95.
Gordin A, Golz A, Daitzchman M, et al: Fluorine-18 fluorodeoxyglucose positron emission
tomography/computed tomography imaging in patients with carcinoma of the
nasopharynx: diagnostic accuracy and impact on clinical management. Int J Radiat Oncol
Biol Phys 2007; 68:370-376.
7. Staging
NPC is staged clinically, as surgery has a limited role in the initial treatment of the
disease. Clinical staging utilizes information from patient history and physical examinations,
imaging studies, laboratory tests, and endoscopy. The American Joint Committee on Cancer
(AJCC) Tumor Node Metastasis (TNM) staging system is the accepted standard for staging of
NPC (Table-4).
Table 4. Clinical staging according to AJCC
Reference
Edge SB, Byrd DR, Compton CC et al (2010) American Joint Committee on Cancer,
American Cancer Society. AJCC cancer staging manual, 7th edn. Springer, Berlin
Heidelberg New York.
Gustavo Arruda Viani
120
8. Routes of Spread
The classification of the various neck node groups (the Robbins Classification)
is illustrated in Figure-4.
Figure 4. Schematic description of the neck node groups: submental (Ia) and submandibular (Ib), upper
jugular (II), mid jugular (III), lower jugular (IV), posterior triangle (V), and anterior compartments (VI).
Lymph node involvement is seen in ~90% of cases at diagnosis; ~50% have bilateral
neck node spread with Level II and retropharyngeal nodes (lateral groups) being considered
the first- nodal groups (figure-5). Dissemination with “skip metastasis” in cervical lymph
nodes is rare. NPC follows an orderly fashion to dissemination generally in the craniocaudal
direction. Isolated contralateral cervical nodal metastasis is uncommon and mediastinal node
spread may occur in patients with supraclavicular adenopathy. Between 1–5% of patients
present with distant metastasis (DM) at diagnosis; but 20–50% present during the course of
the disease. Hematogenous metastases usually occur after cervical lymph node (especially
lower neck nodes) metastases.
Figure 5. Distribution of neck node metastases in nasopharyngeal carcinoma. The size of the nodes is
proportional to the frequency of involvement of the different lymph-node groups.