Malignant Tumors of the Temporal Bone Treatment & Management

Primary radiation is ineffective for curative treatment. In the most extreme cases in which contraindications to surgery are serious deterrents to an operation, palliative radiation and chemotherapy may be offered. The literature supports a beneficial effect of adjunctive radiation on survival, but no well-controlled studies have been performed. Postoperative radiation treatment may be indicated in advanced disease. Most authors advocate full course postoperative radiation to stage T3 or T4 tumors as defined by the University of Pittsburgh staging system. Some authors also recommend radiation for T2 disease. ^[4]

The literature supports a beneficial effect of postoperative radiation on survival. ^{[6, 11]} The temporal bone and neck should be treated with 50-60 Gy for tumors staged T3 and T4. Radiation may also be indicated for smaller lesions.

Preoperative chemotherapy was reviewed by Nakagawa et al in a retrospective series of patients treated with preoperative chemoradiation or with chemoradiation alone). ^[19] Four of 8 patients treated with chemoradiation (5-flourouracil or a fluoropyrimidine complex during external beam radiation with a dose of 40Gy), followed by chemotherapy in one case, were free of disease at 24-47 months. Pemberton et al reported 53% cancer-specific survival of 123 patients treated with radiotherapy alone (55 Gy). ^[20]

A study by Noda et al indicated that nivolumab, an immune checkpoint inhibitor used against platinum-refractory metastatic or recurrent head and neck squamous cell carcinoma, has some therapeutic effect in temporal bone squamous cell carcinoma. The drug was administered to nine patients in whom recurrent or residual temporal bone squamous cell carcinoma was found following platinum-including chemotherapy and/or chemoradiotherapy. The investigators determined that one patient showed a partial response, two had stable disease, and four demonstrated progressive disease, with the size having not been assessed in two cases. Moreover, the 1-year overall survival rate was greater in the patients on nivolumab than in five patients who were not treated with the agent (33.3% vs 20.0%, respectively). ^[21]

Based on a retrospective study and literature review of patients with temporal bone paragangliomas, Prasad et al recommended that elderly patients with advanced forms of these tumors be managed with a wait-and-scan approach, with radiotherapy reserved for the treatment of fast-growing tumors. In the study, among patients with class C or D tumors who underwent wait-and-scan management, the investigators found that the tumor remained stable in 22 of 24 patients who were followed up for less than 3 years and that the paraganglioma remained stable or regressed in 10 of 12 patients who were followed up for 3-5 years. In addition, the tumor remained stable or regressed in five of 11 patients who were followed up for more than 5 years. ^[22]

A literature review, Prasad and colleagues stated, revealed no conclusive evidence that radiotherapy is an effective primary modality for the treatment of either class C or D temporal bone paragangliomas. ^[22]

In general, all patients who are medically able should undergo surgical treatment. The optimal surgery removes all of the cancer en bloc because positive margins are associated with poor survival rates. ^[5] The resection procedures that can be performed for the temporal bone include a modified lateral temporal bone resection, lateral temporal bone resection, subtotal temporal bone resection, and total temporal bone resection. The specific procedures and nomenclature vary among surgeons. Adjunctive surgical procedures, including neck dissection, parotidectomy, and craniotomy, should be performed when indicated. Advanced tumors with intracranial invasion have a grave prognosis, and treatment should probably be limited to palliation with less extensive (and less morbid) surgical procedures.

Determination of tumor stage and medical status assists the surgeon in surgical planning. The goal should be complete tumor removal with preservation of CNs and other vital structures whenever possible. Preoperative planning includes mapping of disease extent by both clinical and radiographic evaluation. Tumor encroachment to the region of the internal carotid artery, sigmoid sinus, or jugular vein requires further investigation such as balloon test occlusion with xenon/CT scan (demonstrating the integrity of the contralateral cerebral artery) or angiography with venous phase (to determine dominance of the cerebral outflow). Consultation with a neurosurgeon may be necessary if involvement of the dura is suspected. The patient's medical status plays a major role in his or her tolerance of a long surgical procedure, postoperative recovery, healing, and postoperative rehabilitation.

Management of the primary site

Hirsch and Chang have described the operative procedures in detail and the indications based on the location and stage of the tumor. ^[23] Medina (1990) described several modifications of the lateral temporal bone dissection (LTBR) based on the location of disease. ^[24]

A modified LTBR removes the EAC and leaves the uninvolved tympanic membrane intact. This type of resection is appropriate for tumors originating in the concha without involvement of the EAC.

The LTBR includes resection of the EAC, tympanic membrane, malleus, and incus. The boundaries are the middle ear cavity and stapes medially, the mastoid cavity posteriorly, the epitympanum and zygomatic root superiorly, the temporomandibular joint (TMJ) capsule anteriorly, and the medial tympanic ring or infratemporal fossa (ITF) inferiorly. The lateral margin depends on the extent of spread. The otic capsule and facial nerve are preserved. The LTBR is appropriate for T1 and T2 tumors.

The LTBR begins with a long, postauricular incision extending from the temporal fossa into the neck. If the pinna is to be preserved, a second incision is made within the concha lateral to the lesion. If the pinna is to be resected, a preauricular incision is incorporated to the postauricular incision allowing the pinna and surrounding skin to be included in the specimen. A cortical mastoidectomy is performed and the facial nerve identified. Bone removal is extended into the zygomatic root and to the digastric ridge. An extended facial recess is made, and the incudostapedial joint is separated. The facial recess is continued inferiorly and anteriorly lateral to the facial nerve, but medial to the annulus, until the specimen is attached only at the anterior canal bony wall at the level of the temporomandibular capsule. An osteotome is used to separate the bony specimen. The parotidectomy is performed en bloc.

A subtotal temporal bone resection (STBR) is performed when invasion medial to the tympanic membrane or into the mastoid (T3 disease) is evident. In this case, the medial margin may be obtained in a piecemeal fashion, usually with a drill. The specimen includes the LTBR with additional dissection of the otic capsule and the medial bony wall of the middle ear and mastoid. The margins of resection are the sigmoid sinus and posterior fossa dura posteriorly, middle fossa dura superiorly, internal carotid artery anteriorly, jugular bulb inferiorly, and petrous apex medially. Based on the extent of tumor spread, dissection may include the condyle of the mandible, the facial nerve, dura, sigmoid sinus, and contents of the infratemporal fossa. The carotid artery is skeletonized and becomes the medial margin.

Tumor involvement of the jugular bulb requires ligation of the inferior jugular vein and proximal control of the sigmoid sinus. The facial nerve is traditionally sacrificed, with the proximal margin taken in the labyrinthine or internal auditory canal segment. However, the surgeon may elect to preserve the nerve if no indication of nerve involvement exists. The medial extent of dissection at the level of the otic capsule depends on the depth of involvement and is done piecemeal. Tumor extension into the protympanum, eustachian tube, or carotid artery is addressed with an infratemporal fossa dissection. The temporalis muscle is reflected and the zygomatic arch removed. The mandibular condyle is resected. The dissection proceeds based on the extent of disease but may include identification of the pterygoid plate, the mandibular nerve (V3), and the horizontal carotid artery and may include a temporal craniotomy.

A total TBR can be used to address T4 disease. However, this procedure is associated with significant morbidity and may not significantly improve survival in these cases of advanced disease. The total TBR includes the STBR with the additional resection of the petrous apex. The internal carotid artery may be isolated, mobilized, and preserved or resected. The sigmoid sinus, jugular vein, carotid artery, dura and CNs are removed as indicated by the extent of the tumor.

Management of the parotid and temporomandibular joint

The intraparotid lymph nodes are a first echelon drainage site for cancers of the EAC and middle ear. An adequate anterior margin for the temporal bone resection routinely involves resection of the parotid gland, temporomandibular joint, and condyle. Resection of these soft tissues will also address minimal soft tissue extension beyond the temporal bone. Ideally, this is performed en bloc with the temporal bone. A superficial parotidectomy is performed with preservation of the facial nerve for T1 and T2 tumors. When the facial nerve is resected for more advanced lesions, a total parotidectomy may be performed.

Management of the neck

Although metastasis to the neck is uncommon in limited cancers of the temporal bone, neck dissections are routinely performed. With more extensive cancers, dissection of the neck offers staging and provides control of the great vessels and exposure to the skull base. However, the presence of metastasis is associated with a poor prognosis, and neck dissection does not improve survival. ^{[11, 6]}

Management of the dura and brain

Although involvement of the dura and brain portend for a poor prognosis, an aggressive approach includes resection of the dura and a small volume of the temporal lobe with a healthy margin.

Reconstruction

Facial nerve grafting is usually not performed in the presence of a malignant lesion. Management of facial nerve paralysis may include CN XII to VII grafting, cross facial grafting, and static procedures. Extensive resections may result in large soft tissue defects. A temporalis muscle flap can be used to fill small to medium defects. The pedicled myocutaneous trapezius flap is an excellent option for reconstruction of the soft tissue and skin defect. The pectoralis flap has limited distant reach to the resected margin. The rectus abdominus free flap and radial forearm flap are particularly suited for the area. Dural defects should be repaired primarily or with graft reconstruction.

Postoperative care consists of monitoring wound complications, flap viability, intracranial complications, and complications of CN deficits. If the dura was resected and repaired, the wound should be observed for a cerebrospinal fluid leak. Supportive care for dizziness, nausea, and vertigo is needed when the otic capsule is entered during the resection. Eye care should be instituted if postoperative facial paralysis develops or if the facial nerve is resected. Resection of CN X requires swallowing and vocal fold rehabilitation and observation for aspiration or airway complications. If the temporomandibular joint was removed, the mandible should be mobilized early to prevent contralateral dysfunction.

Complications of treatment depend on the extent of resection and the use of adjunctive radiation. Postoperative hearing loss, facial nerve paralysis, vertigo, and other CN deficits (eg, CN V, VII, VIII, IX, X, XI) may occur. Dural resection may predispose to cerebral spinal fluid leaks, meningitis, or intracranial complications. Significant complications can result from trauma to or resection of the carotid artery. Radiation has known complications of fibrosis of soft tissues, destruction of salivary gland tissue, osteoradionecrosis of the temporal bone, and possibly central nervous system effects if the field of radiation extends to intracranial tissues.

Prognosis is related to the primary site, the histologic type, and treatment. ^{[25, 26]} The outcome of treatment for early stage tumors is favorable, with most series reporting an 80-100% survival rate. Later stage cancers after adequate surgery and radiation treatment have a survival between 50% and 80%. Advanced lesions have a poor prognosis despite aggressive treatment, with 2-year survival of 0-40%. ^{[11, 6]} Salvage surgery after an incomplete resection is associated with a poorer prognosis compared to a definitive procedure in an undisrupted field. ^[6] A mastoidectomy or limited excision performed by an outside institution prior to referral complicates preoperative assessment and staging, disrupts margins, and forces the surgeon to operate in an inflamed field with interrupted landmarks. Positive margins, nodal disease, dural involvement, and advanced disease are associated with poorer survival. ^{[11, 6]}

A retrospective study by Komune et al of outcomes and prognostic factors in temporal bone squamous cell carcinoma found the 5-year disease-specific survival rate to be higher in stage T1 to T3 cases than in patients with stage T4 tumors, the rates being 100% (T1), 92% (T2), 86% (T3), and 51% (T4). No correlation was found between poor survival and extension of the tumor to the middle ear cavity, as occurred in 13 of 17 stage T3 cases. ^[27]

Another study by Komune et al found, through univariate Cox regression analysis, that in patients with temporal bone squamous cell carcinoma, a poor prognosis is associated with high ratios of neutrophils to lymphocytes and platelets to lymphocytes, a low ratio of lymphocytes to monocytes, a Glasgow Prognostic Score of 2, and a Systemic Inflammation Score of 2. Thus, the report indicated a link between inflammation-based prognostic markers and survival in temporal bone squamous cell carcinoma. ^[28]

A study by Hongo et al indicated that in temporal bone squamous cell carcinoma, the tumor’s immune microenvironment can help to predict prognosis. For example, the investigators reported an association between a high density of CD8⁺ tumor-infiltrating lymphocytes (TILs) and a complete response to chemoradiotherapy. On the other hand, a poorer prognosis was associated with expression of programmed death ligand 1 (PD-L1) (1% or more) and a high density of Foxp3⁺ TILs. ^[29]

A study by Marioni et al indicated that in patients with advanced, aggressive temporal bone squamous cell carcinoma, the risk for tumor recurrence after postoperative radiotherapy is increased in those with a primary tumor classification of 4, a pathologic grade of 2 or 3, and dura mater involvement. ^[30]

The optimal management of temporal bone cancer remains unclear because of continued debate regarding staging, the utility of preoperative radiographic evaluation, the extent and nomenclature of surgical procedures, and the use of adjuvant radiation. The limited number of cases of temporal bone malignancies at each individual institution precludes definitive conclusions regarding the optimum protocol for management. The future of improved treatment strategies lies in a multi-institutional effort to adopt a staging system and develop prospective trials.