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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Oral Cavity Cancer
61
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.
Table 13. Limit doses for organ at risks
Figure 7. The homogeneity and highly conformal dose distributions for oral cavity cancer.
Conclusion
• A single modality treatment, as surgery or radiation therapy, can be preferred for
early-stage oral cavity SCC.
• On the other hand, a combination between surgery followed by adjuvant therapy or
chemoradiation alone is routinely indicated for more advanced disease.
• Nonsurgical organ preservation therapy with chemoradiation therapy is preferred for
most oropharyngeal cancer cases rather than a primary surgery approach.
• Improvements in radiation techniques, as intensity-modulated radiation therapy, and
the use of combined chemotherapy and biological therapy have substantially
improved treatment outcomes.
Oropharyngeal Cancer
In the western world, oropharyngeal carcinomas account for about 5% of all
cancers, and approximately 10,000 new cases of oropharyngeal cancer are
diagnosed in U.S.A. annually.
The majority of patients feel a mass in throat posteriorly. Lymph node
metastasis at diagnostic is frequent. Thus, neck mass may be the first symptom
at presentation.
Histologic confirmation (fine-needle aspiration [FNA] of a suspected lymph
node or open biopsy of the primary disease) is sufficient and critical in
determining the histopathology and extent of disease spread to radiologically
indeterminate nodes.
Squamous cell carcinomas account for more than 90 percent of the lesions in the
orapharynx.
Local extension and lymphatic spread are the most common patterns of
dissemination. Regional spread is predictable and orderly dependent on location
in the oropharynx, the laterality of the tumor, the depth of invasion, and the
presence of ipsilateral nodal disease
Nodal involvement is the single most important prognostic factor, which
determines survival and upstages to advanced disease.
Early squamous cell carcinomas of the oropharynx can be treated with either
surgery or radiation therapy (RT) as a single modality. Definitive RT and
primary surgery have yielded similar rates of local control and survival.
For most patients with locally advanced oropharyngeal cancer, an organ
preservation strategy rather than surgical resection have been suggested.
Concurrent chemoradiation and sequential therapy (induction chemotherapy
followed by concurrent chemoradiotherapy) are effective organ function
preservation approaches.
Chapter 5
Abstract
Introduction
The management of oropharynx cancer remains difficult despite recent advances in
surgical and radiotherapy techniques. Many patients present at an older age with advanced
Gustavo Arruda Viani
64
Tobacco
smoking
It is the single most important etiologic factor.
Tobacco contains more than 19 known carcinogens and more than 4,000 chemicals
carcinogenic.
Diet
Approximately 15% of oral and oropharyngeal cancers can be attributed to dietary
deficiencies.
Increase in risk has been reported with high intake of foods that represent important
source of calories, such as starchy foods, pulses, certain meats especially processed
meat, charcoal grilled
meat, pork, and eggs.
disease because of the occult nature of associated symptoms. The disease process and
treatment often affect adjacent structures, such as oral cavity and the larynx. Clinical outcome
is determined primarily by extent of disease, and treatment modality. Careful
multidisciplinary assessment and treatment selection based on the probability of cure and
preservation of function are of paramount importance in the treatment of these patients. In
this chapter we will discuss the role of radiotherapy in the management of these tumors.
1. Epidemiology
• Oropharyngeal cancer is a relatively uncommon malignancy, with approximately
123,000 cases diagnosed worldwide each year, and about 79,000 deaths.
• In the western world, oropharyngeal carcinomas account for about 5% of all cancers,
and approximately 10,000 new cases of oropharyngeal cancer are diagnosed in
U.S.A. annually.
• The incidence of oropharyngeal cancer varies considerably around the world, but in
most series it ranks second or third in order of frequency of head and neck cancers
and in general is not as common as laryngeal or oral cavity tumors.
• The disease is more common in males with the male/ female ratio ranging between 2
and 5:1 and is seen most frequently in the sixth and seventh decade in men and
women.
• Some recent reports indicate toward an increasing trend of oral and oropharyngeal
cancer among younger population around the globe.
References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin.
2005;55(2):74.
2. Risk Factors
Several risk factors have been identified for head and neck cancer from oropharynx
(Table-1).
Table 1. Risk factors for oropharyngeal cancer
Oropharyngeal Cancer
65
Alcohol
Alcohol use has a synergistic effect with tobacco and is known to increase the risk of
developing head and neck SCC (HNSCC) up to 20 to 120 times than of nonsmoker and
nonalcoholic person
Human
papilloma virus
(HPV)
HPV infection is particularly associated with young, sexually active, nonsmoker males
and may be responsible for changing trends of oral and oropharyngeal cancers toward
younger nonsmoking population
Other factors
Chronic irritants, poor dental hygiene, candidiasis, syphilis, and marijuana smoking
References
Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, Boyle P. Tobacco
smoking and cancer: a meta-analysis. Int J Cancer. 2008;122(1):155.
Hashibe M, Brennan P, Benhamou S et al. Alcohol drinking in never users of tobacco,
cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis
in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer
Inst. 2007;99(10):777.
3. Anatomy
The pharynx is a musculomembranous tube suspended from the skull base to the level of
the sixth cervical vertebra, supported by overlapping constrictor muscles (superior, middle,
and inferior) and other muscles arising from the styloid process and skull base. This
musculomembranous conduit communicates with the oral cavity anteriorly, the nasopharynx
superiorly, and the hypopharynx and larynx inferiorly. It is divided into four sites of clinical
importance: the tonsillar area, which makes up the major portion of the lateral pharyngeal
wall and blends with the tongue base, soft palate, and retromolar trigone; the tongue base; the
soft palate; and the posterior pharyngeal wall. Innervation of the pharynx is via the
pharyngeal plexus, with contributions from the glossopharyngeal (sensory) and vagus nerves
(figure – 1).
4. Clinical Features
• The majority of patients feel a mass in throat posteriorly. Lymph node metastasis at
diagnostic is frequent.
• Thus, neck mass may be the first symptom at presentation. Only 4 to 10% of patients
are stage I at presentation, roughly 10 to 20% are stage II, and about 70% are stage
III and IV.
• The reason for late presentation of disease is the vagueness of initial presenting
symptoms such as soreness or discomfort in the throat particularly on swallowing
and otalgia that are reported in about 38 and 6% of the patients, respectively.
• The risk of bilateral neck node metastases is very high, especially in base of tongue
cancers.
• In more advanced disease, dysfunctions in swallowing, oral fetor, bleeding,
hemoptysis, fixed tongue, trismus, and weight loss may be seen.
Gustavo Arruda Viani
66
• The risk of distant metastasis is higher than that for the oral cavity. Furthermore, the
presence of a secondary malignancy or later development in the upper or lower
airways is also higher.
Figure 1. Oropharyngeal anatomy.
5. Diagnosis and Evaluation
• Histologic confirmation (fine-needle aspiration [FNA] of a suspected lymph node or
open biopsy of the primary disease) is sufficient and critical in determining the
histopathology and extent of disease spread to radiologically indeterminate nodes.
• Indirect laryngoscopy with a mirror should be performed to see the base of the
tongue and vallecula.
• A tumor in this region may easily invade the surrounding soft tissues and present at
more advanced stages. However, the actual size of the tumor is determined by
bimanual palpation and advanced imaging modalities (MRI, CT), as described in
figure-2.
• Evaluation of the upper aerodigestive tract is crucial to evaluate the primary site of
disease and the presence of synchronous primaries.
• CT scans of the neck and chest are appropriate to evaluate and stage head and neck
cancer. FDG-PET/CT scan is recommended for diagnosis, staging, and surveillance
of head and neck cancer.
• After treatment, PET/CT may be used to monitor for persistent disease in the neck or
primary site and is best done 3 months after the end of radiation therapy.
Oropharyngeal Cancer
67
a b
Figure 2. base of tongue cancer imaged with(a) CT and (b) MRI showing a large mass on the left side
of the oropharynx involving the base of tongue and the left tonsillar fossa with invasion of the left
parapharyngeal space. The base of tongue mass extends past the midline. These features are better
visualized using MRI than CT.
References
Tandon S, Shahab R, Benton JI, Ghosh SK, Sheard J, Jones TM. Fine-needle aspiration
cytology in a regional head and neck cancer center: comparison with a systematic review
and meta-analysis. Head Neck. 2008;30(9):1246.
Prehn RB, Pasic TR, Harari PM, Brown WD, Ford CN. Influence of computed tomography
on pretherapeutic tumor staging in head and neck cancer patients. Otolaryngol Head
Neck Surg. 1998;119(6):628.
Rasch C, Keus R, Pameijer FA et al. The potential impact of CT-MRI matching on tumor
volume delineation in advanced head and neck cancer. Int J Radiat Oncol Biol Phys.
1997;39(4):841.
6. Pathology
Squamous cell carcinomas account for more than 90 percent of the lesions in the oral
cavity. These tumors can be categorized as well differentiated (greater than 75 %
keratinization), moderately differentiated (25-75 % keratinization) and poorly differentiated
(less than 25 percent keratinization) tumors. Other less common histologies include verrucous
carcinoma, a variant of squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma,
and mucoepidermoid carcinomas. In additional, some Premalignant lesions of the oral cavity
have a potential for malign transformation (table-2).
Gustavo Arruda Viani
68
Type
Description
Leukoplakia.
It is the most common premalignant lesion in the head–neck region.
The white macules may have several histological features, from simple
hyperkeratosis, dysplasia and carcinoma in situ to invasive carcinoma.
The risk of malignant transformation in these lesions is higher in smokers and in
women.
Erythroplakia.
It is less common than leukoplakia. The risk of malignant transformation is much
higher, and biopsy is essential for histological evaluation.
Lichen planus.
Erosive lichen planus in the oral cavity may transform into malignancy.
The erosive type is seen in the floor of the mouth. Biopsy is essential to
determine lichen type and for differential diagnosis from leukoplakia.
Table 2. Premalignant lesions for oropharyngeal cancer
Reference
World Heath Organization Classification of Tumors: Pathology and Genetics: Head and Neck
Tumors, Barnes L, Everson JW, Reichart P, Sidransky D (Eds), WHO Press, Switzerland
2005.
7. Routes of Spread
• Local extension and lymphatic spread are the most common patterns of
dissemination.
• Regional spread is predictable and orderly dependent on location in the oropharynx,
the laterality of the tumor, the depth of invasion, and the presence of ipsilateral nodal
disease (Table-3 and 4).
• The incidence of nodal metastases in oropharyngeal SCC is reported to vary from 12
to 85%.
• In majority of cases it is nearer to the higher values of spectrum (50%–85%) (Table-
3) and may be influenced by a number of potential tumor factors including grade of
differentiation, site, and size of the tumor.
• Despite numerous lymphatic pathways and cervical lymph nodes, the lymphatic
spread of oropharyngeal cancers usually occurs in a predictable way from superior to
inferior, the upper deep cervical lymph nodes (level II) being the first echelon at risk.
References
Shah JP, Candela FC, Poddar AK (1990) Patterns of cervical lymph node metastases from
SCC of the oral cavity. Cancer 66:109–113;
Shah JP (1990) Patterns of cervical lymph node metastasis from SCC of the upper
aerodigestive tract. Am J Surg 160:405–409
Oropharyngeal Cancer
69
Primary tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 2 cm or less in greatest dimension
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3 Tumor more than 4 cm in greatest dimension or extension to lingual surface of epiglottis
T4a Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible*
T4b Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid
artery
Regional lymph nodes (N)•
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or
in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral
lymph nodes, none more than 6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Distant metastasis (M)
M0 No distant metastasis
M1 Distant metastasis
8. Staging
The tumor node metastases (TNM) system of the American Joint Committee on Cancer
(AJCC) and the International Union for Cancer Control (UICC) have been used to stage
hypopharyngeal cancers (table-3).
Table 3. TNM staging system for oropharyngeal cancer
Reference
American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton
CC, et al (Eds), Springer, New York 2010.
9. Prognostic Factors
• Staging. The AJCC stage represents an important prognostic factor. Nodal
involvement is the single most important prognostic factor, which determines
survival and upstages to advanced disease.
• Postoperative finds. Presence of extracapsular extension or positive margins is
important predictors of locoregional recurrence and survival.
• Performance status and gender. Other negative factors include poor performance
status and male gender.
• HPV. Human papilloma virus is implicated in the transformation of oropharynx with
the subtype HPV-16 most associated with malignancy. HPV-positive oropharyngeal
cancers have an improved prognosis related either to the biology of these tumors or
the lack of associated.
Gustavo Arruda Viani
70
Studies
Description
Chera et al
(2008)
145 patients treated with curative intent were included. Potential follow-up was>or =2
years.
Local control rates at 5 years were: T1, 90%; T2, 91%; T3, 67%; T4, 57%. Nodal
control rates at 5 years were: N0, 90%; N1, 82%; N2, 68%; N3, 71%.
Ultimate local-regional control rates at 5 years were: stage I, 89%; stage II, 88%;
stage III, 96%; stage IVA, 63%; stage IVB, 43%.
In multivariate analysis, overall treatment time significantly affected local and
ultimate local-regional control, and nodal stage significantly affected overall survival.
Overall survival rate at 5 years was 44%. Cause-specific survival rate at 5 years was
73%.
Erkal et al.
(2001)
107 patients treated with curative intent with RT alone or followed by neck dissection
from were included. All patients had follow-up for at least 2 years.
Local control rates at 5 years were 86% for T1, 91% for T2, 67% for T3, and 36% for
T4 carcinomas. T-stage and overall treatment time significantly affected local control
in multivariate analysis.
Nodal control rates at 5 years were 86% for NO, 76% for N1, 61% for N2, and 67%
for N3 carcinomas.
Ultimate local-regional control rates at 5 years were 90% for Stage I, 92% for Stage
II, 84% for Stage III, and 60% for Stage IV disease.
The overall survival rate at 5 years was 42% for all patients.
Reference
Sessions DG, Lenox J, Spector GJ, Chao C, Chaudry OA. Analysis of treatment results for
base of tongue cancer. Laryngoscope. 2003;113(7):1252.
10. Treatment
10.1. Early Stage Disease
Soft Palate
• Early squamous cell carcinomas of the oropharynx can be treated with either surgery
or radiation therapy (RT) as a single modality.
• Definitive RT and primary surgery have yielded similar rates of local control and
survival in retrospective studies, although there are no prospective randomized trials
comparing the two approaches.
• The morbidity associated with each treatment approach is an important factor in
making treatment decisions.
• RT is used more commonly, but surgery may be preferred in selected situations. The
risk of occult neck metastases in a patient with oropharyngeal cancer and a clinically
negative neck is relatively high. Thus, elective treatment of the neck is generally
performed (table-4).
Table 4. Clinical evidence for curative treatment in soft palate cancer