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Nasopharyngeal Cancer (PDQ®) Treatment - Health Professionals
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Table of Contents
General Information
Cellular Classification
Stage Information
TNM definitions
AJCC stage groupings
Stage 0
Stage I
Stage IIA
Stage IIB
Stage III
Stage IVA
Stage IVB
Stage IVC
Treatment Option Overview
Stage I Nasopharyngeal Cancer
Stage II Nasopharyngeal Cancer
Stage III Nasopharyngeal Cancer
Stage IV Nasopharyngeal Cancer
Recurrent Nasopharyngeal Cancer
General Information
The nasopharynx has a cuboidal shape. The lateral walls are formed by the eustachian tube and the
fossa of Rosenmuller. The roof, sloping downward from anterior to posterior, is bordered by the
pharyngeal hypophysis, pharyngeal tonsil, and pharyngeal bursa with the base of skull above.
Anteriorly, the nasopharynx abuts the posterior choanae and nasal cavity, and the posterior boundary is
formed by the muscles of the posterior pharyngeal wall. Inferiorly, the nasopharynx ends at an
imaginary horizontal line formed by the upper surface of the soft palate and the posterior pharyngeal
wall. Unlike other squamous cell cancers of the head and neck, nasopharyngeal cancer does not appear
to be linked to excess use of
tobacco and alcohol. Factors thought to predispose to this tumor include Chinese (or Asian) ancestry,
Epstein-Barr virus(EBV) exposure, and as yet unknown factors that result in very rare familial
clusters.1
Symptoms and signs at presentation include painless, enlarged lymph nodes in the neck (present in
approximately 75% of patients and often bilateral and posterior), nasal obstruction, epistaxis,
diminished hearing, tinnitus, recurrent otitis media, cranial nerve dysfunction (usually II-VI or IXXII), sore throat, and headache. In the patient who presents with only cervical adenopathy, the finding
of EBV genomic material in the tissue after amplification of DNA with the polymerase chain reaction
lends strong evidence for a nasopharyngeal primary tumor, and a concerted search should be conducted
in that area.2
Tumors of many histologies can occur in the nasopharynx but this discussion, like the American Joint
Committee on Cancer nasopharynx staging, refers exclusively to those of squamous cell type.
Diagnosis is made by biopsy of the nasopharyngeal mass. Work-up includes careful visual examination
(by mirror or endoscopic examination); documentation of the size and location of the tumor and neck
nodes; evaluation of cranial nerve function and hearing; skull films (especially base of skull views),
evaluating neural foramina; complete computed tomographic (CT) scan or magnetic resonance imaging
(MRI) with views delineating the upper and lower extent of the lesion; chest x-ray; hemogram; and
chemistry panel. Any clinical or laboratory suggestion of distant metastasis may prompt further
evaluation of other sites. Careful dental and oral hygiene evaluation and therapy is particularly
important prior to initiation of radiation treatment. MRI is often more helpful than CT scans in
detecting abnormalities and in defining their extent.3-5
1
Major prognostic factors adversely influencing outcome of treatment include large size of the tumor,
higher T stage, and the presence of involved neck nodes.6 Other factors linked to diminished survival
in some, but not all, studies include age, nonlymphoepithelial histology, long interval between biopsy
and initiation of radiation therapy, diminished immune function at diagnosis, incomplete excision of
involved neck nodes, pregnancy during treatment, loco-regional relapse, and certain EBV antibody titer
patterns.
Small cancers of the nasopharynx are highly curable by radiation therapy, with survival rates of
80% to 90%.7 Moderately advanced lesions without clinical evidence of spread to cervical lymph
nodes are often curable, with survival rates of 50% to 70%.
Patients with advanced lesions, especially those associated with clinically positive cervical lymph
nodes, cranial nerve involvement, and bone destruction, are poorly controlled locally by radiation
therapy with or without surgery and often develop distant metastases despite local control.8,9
Although most recurrences occur within 5 years of diagnosis, relapse can be seen at longer intervals.
The incidence of second primary malignancies appears less than other head and neck sites.10
Follow-up for patients includes routine periodic examination of the original tumor site and neck, chest
x-ray, MRI or CT scan, and blood work. Monitoring of patients should include surveillance of thyroid
and pituitary function; dental and oral hygiene; jaw exercises to avoid trismus; evaluation of cranial
nerve function, especially those related to vision and hearing; and evaluation of systemic complaints to
identify distant metastasis.
Poorly differentiated squamous cancer has been associated with EBV antibodies.2,11 High titer
antibodies to virus capsid antigen and early antigen, especially of high IgA class, or high titers that
persist after therapy have been associated with a poorer prognosis. This finding remains under
evaluation.
Cellular Classification
Although a wide variety of malignant tumors may arise in the nasopharynx, only squamous cell
carcinoma is considered in this discussion because management of the others varies substantially with
histology. Subdivisions of squamous in this site include lymphoepithelioma (Schminke tumor);
transitional cell tumors, well to poorly differentiated grade; and keratinizing or nonkeratinizing
variety.1 The presence of keratin has been associated with reduced local control and survival.2,3
Stage Information
Staging systems are all clinical staging, based on the best possible estimate of the extent of disease
before treatment.1,2 Assessment of the primary tumor is based on inspection and palpation when
possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor
must be confirmed histologically, and any other pathologic data obtained on biopsy may be included.
Evaluation of the function of the cranial nerves is especially appropriate for tumors of the nasopharynx.
The appropriate nodal drainage areas are examined by careful palpation.3,4 Information from
diagnostic imaging studies may be used in staging. Magnetic resonance imaging offers an advantage
over computed tomographic scanning in the detection and localization of head and neck tumors and the
distinction of lymph nodes from blood vessels.5 If a patient has a relapse, a complete reassessment
must be done to select the appropriate additional therapy.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to
define nasopharyngeal cancer.6
2
TNM definitions
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor confined to the nasopharynx
T2: Tumor extends to soft tissues of oropharynx and/or nasal fossa
T2a: without parapharyngeal extension
T2b: with parapharyngeal extension
T3: Tumor invades bony structures and/or paranasal sinuses
T4: Tumor with intracranial extension and/or involvement of cranial nerves,
infratemporal fossa, hypopharynx, or orbit
Regional lymph nodes (N)
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 fossa
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)
N3a: greater than 6 cm in dimension
N3b: extension to the supraclavicular fossa
Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
AJCC stage groupings
Stage 0
Tis, N0, M0
Stage I
T1, N0, M0
Stage IIA
T2a, N0, M0
Stage IIB
T1, N1, M0
T2, N1, M0
T2a, N1, M0
T2b, N0, M0
T2b, N1, M0
Stage III
T1, N2, M0
T2a, N2, M0
T2b, N2, M0
T3, N0, M0
T3, N1, M0
T3, N2, M0
Stage IVA
T4, N0, M0
T4, N1, M0
T4, N2, M0
Stage IVB
3
Any T, N3, M0
Stage IVC
Any T, Any N, M1
Results of radiation therapy for nasopharyngeal carcinoma (local-regional control and survival) are
usually reported by T stage and N stage separately or by specific T and N subgroupings rather than by
numerical stages I to IV. Outcome also depends on a variety of biologic and technical factors related to
treatment.
Treatment Option Overview
High-dose radiation therapy is the primary treatment of nasopharyngeal cancer, both for the primary
tumor site and the neck. Surgery, when feasible, is usually reserved for nodes that fail to regress after
radiation or for nodes that reappear following clinical complete response. Radiation therapy dose and
field margins are individually tailored to the location and size of the primary tumor and lymph nodes.14 Although most tumors are treated with external-beam irradiation exclusively, in some tumors
radiation therapy may be boosted with radioactive intracavitary or interstitial implants when clinical
expertise is available and the anatomy is suitable.5-8 A review of published clinical results of radical
radiation therapy for head and neck cancer suggests a significant loss of local control when the
administration of radiation therapy was prolonged; therefore, lengthening of standard treatment
schedules should be avoided whenever possible.9
Accumulating evidence has demonstrated a high incidence (>30%-40%) of hypothyroidism in patients
who have received radiation that delivered external- beam irradiation to the entire thyroid gland or to
the pituitary gland. Thyroid-function testing of patients should be considered prior to therapy and as
part of post-treatment follow-up.10,11 The designations in PDQ that treatments are "standard" or
"under clinical evaluation" are not to be used as a basis for reimbursement determinations.
Stage I Nasopharyngeal Cancer
Treatment options:
Standard: High-dose radiation therapy to the primary tumor site and prophylactic radiation
therapy to the nodal drainage.1-3
Stage II Nasopharyngeal Cancer
Treatment options:
Standard:
1. Chemoradiotherapy.1[Level of evidence: 3iiiA]
2. High-dose radiation therapy to the primary tumor site and prophylactic radiation therapy to
the nodal drainage.2-4
Stage III Nasopharyngeal Cancer
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial
boards use a formal ranking system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Treatment options:
Standard:
1. Chemoradiotherapy.1,2
2. High-dose or superfractionated radiation therapy to the primary tumor site and bilateral
neck nodes that are clinically positive.3-6
3. Neck dissection may be indicated for persistent or recurrent nodes if the primary tumor site
is controlled.5
Under clinical evaluation:
Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors, thereby rendering
them more
definitively treatable with radiation. Chemotherapy is given prior to the other modalities,
hence the designation
neoadjuvant to distinguish it from standard adjuvant therapy, which is given
after or during definitive therapy with
radiation or after surgery. Many drug combinations have been
4
used in neoadjuvant chemotherapy. Two randomized
prospective trials compared combination
chemotherapy (cisplatin, epirubicin, and bleomycin or cisplatin plus 5-FU
injections) plus radiation
therapy to radiation therapy alone.1[Level of evidence: 1iiA];7[Level of evidence: 1iiDi]
Although
disease-free survival was improved in the chemotherapy group for both groups, improvement in overall
survival
was reported only from the intergroup.1
Clinical trials for advanced tumors evaluating
the use of chemotherapy before radiation therapy, concomitant with
radiation therapy, or as adjuvant
therapy after radiation therapy should be considered.8-11 References:
Stage IV Nasopharyngeal Cancer
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial
boards use a formal ranking system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Treatment options:
Standard:
1. Chemoradiotherapy.1,2
2. High-dose or superfractionated radiation therapy to the primary tumor site and bilateral
lymph nodes that are clinically positive.3-6
3. Neck dissection should be reserved for persistent or recurrent nodes.5
4. Chemotherapy for patients with stage IVC disease.
Under clinical evaluation:
Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors, thereby rendering
them more
definitively treatable with radiation. Chemotherapy is given prior to the other modalities,
hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given
after or during definitive therapy with radiation or after surgery. Many drug combinations have been
used in neoadjuvant chemotherapy. Two randomized prospective trials compared combination
chemotherapy (cisplatin, epirubicin, and bleomycin or cisplatin plus 5-FU
injections) plus radiation
therapy to radiation therapy alone.1[Level of evidence: 1iiA];7[Level of evidence: 1iiDi]
Although
disease-free survival was improved in the chemotherapy group for both groups, improvement in overall
survival
was reported only from the intergroup.1 Clinical trials for advanced tumors to evaluate the
use of chemotherapy before radiation therapy, concomitant with
radiation therapy, or as adjuvant
therapy after radiation therapy should be considered.8-11
Recurrent Nasopharyngeal Cancer
Treatment options:
Standard:
1. Selected patients may be re-treated with moderate-dose external-beam radiation therapy
using limited ports and an intracavitary or interstitial irradiation boost to the site of recurrence.1-4
2. In highly selected patients, surgical resection of recurrent lesions may be considered.
3. If a patient has metastatic disease or local recurrence that is no longer amenable to surgery
or radiation, chemotherapy should be considered.5,6
Under clinical evaluation:
Clinical trials such as those evaluating chemotherapy and interferon should be considered.7
5