Cancers of the Nasopharynx

General

  • Highest incidence in China and Eskimos.
  • Peak years in the 4th and 5th decades.
  • Etiology includes viral (EBV), genetic (HLA A2 and HLA BSIN2), and environment (dust and diet due salted fish).
  • 2.4 male:: 1 female

Pathology

WHO classification Prevalence Former Terminology Risk Factors Radiosensitivity and control
Type 1. keratinizing Squamous cell carcinoma 20% US Squamous cell Associated with EtOH and Tob but not EBV Same as other H&N cancers
Type 2. Nonkeratinizing Squamous cell carcinoma +/- lymphoid stroma 30-40% US Transitional cell, Intermediate cell, Lymphoepithelial (Regaud) Positive for anti-EBV See note
Type 3. Undifferentiated carcinoma +/- lymphoid stroma 40-50% US; 99% in endemic areas (eg. SE China) Anaplastic
Clear cell
Lymphoepithelial (Schminke)
Positive for anti-EBV see note

Note: Lymphoepithelioma may be radiosensitive and have better LRC but same OS due to distant failures; Lymphoepithelial more often small, submucosal, and sometimes difficult to detect; indeed, they may be clinically occult.

  • Rare tumors are lymphoma, adenocarcinoma, plasmacytoma, melanoma, and sarcoma.

Juvenile Nasopharyngeal Fibroma (Non-malignant)

  • also called angiofiromas
  • benign, strongly vascularized tumors in H&N region
  • intracranial spread occurs in 25% of cases
  • JNF require several months after RT to remit
  • sometimes complete remission does not occur after years, although there is no further growth.

Anatomy

  • Cuboid area from the base of skull behind the nasal cavity.
    • begins anteriorly at the posterior choana
    • soft palate
    • lateral walls (vault)

Clinical Presentation

  • epitaxis, decreased hearing, and nasal obstruction.

Routes of Spread

  • Inferior: orophaynx
  • Anterior: nasal cavity
  • Posterior: clivus

Superior

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  • superiorly the spinoid sinus (CN VI and V2 are most commonly involved).
  • Petrosphenoidal Syndrome: all the of the cavernous sinuses are involved. CN III, IV, VI ,V1, & V2.

Lateral

  • The lateral walls, which is the most common site for NPX CA, contain the Eustachian tube and the fossa of Rosenmuller.
  • The upper lateral walls only have 2 layers the pharyngeal aponeurosis and the mucous membrane.

Parapharyngeal space

  • contains the lateral retropharyngeal nodes,
  • internal jugular vein, internal carotid artery,
  • CN IX, X, XI, XII
  • and the cervical sympathetic chain.

Nodal Risk

  • 90% ipsilateral with 50% bilateral at presentation and typically the retropharyngeal nodes are affected. Subclinical disease is about 70%.
  • elective irradiation of the level II-V nodes and retrophrengeal nodes bilaterally, regardless of the status of the neck.

Distant metastasis

  • 3% to bones, lung, and liver.

Definitive Surgery

* small tumors that are restricted to postrior nasal cavity and the nasopharynx
* 100% local control

Definitive Radiation

  • Radiotherapy is the mainstay of treatment and chemotherapy is added as an adjuvant in advanced cases.
Early Stage (T1, T2a and N0) RT alone
Advanced Stage (T3, T4 or N1+)
Intergroup (Al-Sarraf JCO 1998)
Chemoradiation
followed by adjuvant Cisplatin and 5-FU for 3 cycles.
Altered fraction/Post-operative RT No role

Radiation Dose

  • ≥ 70 Gy to tumor and gross LN
  • Lymphoepithelioma may be give 500 cGy less.
  • ≥ 50 Gy to nodal regions.

Radiation Field

  • Areas to Cover: CTV56-59.4 (RTOG 0615)
    • entire nasopharynx
    • anterior 1/2 to 2/3 of the clivus (entire clivus, if involved),
    • skull base (foramen ovale and rotundum bilaterally must be included for all cases),
    • pterygoid fossae,
    • parapharyngeal space,
    • inferior sphenoid sinus (in T3-T4 disease, the entires phenoid sinus)
    • and posterior fourth to third of the nasal cavity and maxillary sinuses (to ensure pterygopalatine fossae coverage).
    • The cavernous sinus should be included in highrisk patients (T3, T4, bulky disease involving the roof of the nasopharynx).
  • Lymph nodes groups to cover
    • bilateral submandibular Ib if LN+.
    • bilateral II-V
    • retropharyngeal LN

Complications

  • xerostomia, otitis media, trismus, neck fibrosis, STS, CN dysfunction, myelitis, retinopathy, and optic nerve - increases with increasing fraction size).

Results

T stage LC OS-5
T1 95% 75%
T2 80% 65%
T3 70% 55%
T4 70% 30%
  • Patients who do better Lymphoepithelioma (LC about 90-100%) and undifferentiated carcinoma, younger, females.

OS with RT is about 60%. For early lesions, the LC is about 80%

Reirradiation

Brachytherapy

  • Superfical persitence or recurrence (MGH)
  • 40 Gy EBRT in 20 fractions
  • 20 Gy in 2 applications to mucosal surface

EBRT

  • Deep persistence or recurrence
  • EBRT > 60 Gy (0% OS-5 < 60 Gy vs 45% for > 60 Gy)
  • total mucosal dose ~ 125 Gy.
  • Complications worse for total doses > 100 Gy

SBRT

  • SRT effective, lower risk than reported SRS [2]
  • 15-20 Gy with < 8 Gy to optic chiasm, brainstem and cavernous sinus

IMRT Re-irradiation DVH criteria[4]

  • 10 Gy and 10% for brainstem
  • 4 Gy & 5% for spinal cord
  • 8 Gy & 5% for optic nere and chiasm
  • 10 Gy and 5% for orbit
  • 10 Gy & 10% for temporal lobe

Toxicities

  • ototoxicity 10%
  • crainal neuropathy 10%
  • brain necrosis 7%
  • soft-tissue necrosis/fibrosis 3%

Studies

Study Pts, N LCR, % 5-Yr OS Complication, %
Hwang, 98 74 49 37 23
Yan, 83 162 14 23 34
Vikram, 86 15 61 55 20
Wang, 87 51 45 4
Pryzant, 92 53 35 21 15
Wei, 93 34 63 33 20

Metastatic (M1) NPC

  1. Cisplatin based chemotherapy (20% CR rates)
  2. For patients with CR some institutions give definitive RT alone to H&N as 20% have long term survival.
Bibliography
1. Italian, 1988 (1979-83): PMID 3047335 — "Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study." Rossi A et al. J Clin Oncol. 1988 Sep;6(9):1401-10.
2. Guangzhou; 2007 (China)(1999-2005) PMID 17601682 — "Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma." (Wu SX, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):761-9.)
3. Harvard; 1987 PMID 3597157 — "Re-irradiation of recurrent nasopharyngeal carcinoma—treatment techniques and results." Wang CC et al. Int J Radiat Oncol Biol Phys. 1987 Jul;13(7):953-6.
4. Chua; Reirradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy. Radiotherapy and Oncology 77 (2005): 290-294.
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