The importance of flaps in reconstruction of locoregionally advanced lateral skull-base cancer defects: a tertiary otorhinolaryngology referral centre experience

Lateral skull-base cancer can be classified according to the anatomical site into five categories (an adaptation of Homer et al.³):

The cancer histological type depends upon the abovementioned site.³ Regardless the site, the squamous cell carcinoma is the most common type which accounts for more than 40% of all primary lateral skull-base cancers, followed by basal cell carcinoma in 10%, adenoid cystic carcinoma in 8–10% and melanoma is less than 5%.⁷

The clinical presentation of lateral skull-base cancer is not pathognomonic since it can mimic the chronic inflammatory diseases, such as chronic otitis media, chronic otitis externa, necrotising otitis externa or vasculitis (e.g., granulomatosis with polyangiitis). For that reason, bloody otorrhoea, hearing loss, bleeding, chronic otalgia, facial swelling or palsy and mass should be attributed to the lateral skull-base cancer until proven otherwise. Granulation tissue, nonhealing ulcer or erosion should be elucidated by histopathological examination. In case of progressive pain in the temporomandibular joint area, trismus, facial pain and fullness or subtle mass immediately above zygoma, suspicion of infratemporal fossa cancer should be raised.³

Diagnosis of lateral skull-base cancer mainly comprises histopathological or cytopathological verification, high-resolution computed tomography (CT) and magnetic resonance imaging (MRI) of skull-base and adjacent structures (i.e. parotid region, neck), neck CT or ultrasonography (US) and further evaluation of signs of systemic cancer spread (e.g., abdominal CT/US, chest CT/x-ray, positron emission tomography-CT).³

The clinical examination and diagnostic procedures enable the assessment of tumour stage according to the TNM classification system. Primary tumour (T), regional lymph node metastases (N) and distant metastases (M) can be assessed according to the primary tumour site: e.g. for skin carcinoma of the head and neck, major salivary glands, malignant melanoma of the skin, tumours of bone and soft tissue. EACC and MEC deserve particular emphasis in T, N and M assessment as the AJCC and UICC grading systems do not include these cancer types. EACC should be graded with the modified Pittsburgh staging system (Table 1)^8,9, which has the highest prognostic accuracy.¹⁰ This staging system should be used in pathological TNM staging also.¹¹ MEC has been graded with many staging systems including modified Pittsburgh staging system^18,9 and Stell and McCormick grading system.¹²

After the diagnosis has been established, the patient should be presented at the multidisciplinary tumour board to determine the treatment modalities and goals.³ In our tertiary referral centre, the board, usually consists of an otorhinolaryngologist subspecialised in otologic and lateral skull-base surgery, otorhinolaryngologist subspecialised in head and neck surgery and free flap reconstruction, radiation oncologist and medical oncologist.

The best prognosis of lateral skull-base cancer is achieved with the radical surgical treatment, which depends on the tumour’s extent and presence of regional lymph node metastasis.⁷ Therefore, it can include for an example wide local excision of the tumour, temporal bone resection (lateral, subtotal or total), parotidectomy (superficial or total), neck dissection (selective, modified radical, radical) and temporomandibular joint resection. When the histopathological examination of the resected specimen implies an increased risk of local/regional tumour re-appearance, adjuvant treatment must be considered. Other non-surgical treatment modalities (i.e., radiotherapy, systemic therapy), when indicated, can significantly improve the rate of local and/or regional control.⁷

Since the extensive surgery of locoregionally advanced lateral skull-base cancer results in large tissue defects, the reconstruction should be planned immediately. An assortment of free flaps can be considered to aid the reconstruction such as radial forearm free flap (RFFF), deep inferior epigastric perforator flap, latissimus dorsi free flap and anterolateral thigh free flap (ALT).³ ALT is considered a workhorse in lateral skull-base reconstruction since it provides an adequate tissue bulk to fill the tissue defect. Additionally, the donor site (i.e., thigh wound) can be used to harvest fascia lata to reconstruct dural defect or statically suspend the oral commissure if the facial nerve has been sacrificed. Moreover, ALT can be harvested as chimaeric, i.e. incorporating the lateral cutaneous femoral nerve, which can be used as interposition nerve graft in facial nerve reanimation. It is recommended that facial nerve reanimation should be initiated at primary surgery. However, in certain circumstances (i.e., peripheral arterial occlusive disease, head and neck scarring after the previous radiotherapy) free flaps cannot be used or have failed to reconstruct the defect.³ For that reason, regional flaps such as the pectoralis major myocutaneous flap (PM) should be harvested.^3,13,14

The treatment of lateral-skull base cancer should be reserved for highly specialised centres. This manuscript aims to provide an experience of a single tertiary otorhinolaryngology referral centre in the treatment of this pathology, emphasising the role of regional and free flaps in reconstruction after resection of locoregionally advanced lateral skull-base cancer.

A retrospective case review of patients treated at the Institute of Oncology Ljubljana, Slovenia and/or Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre, Ljubljana, Slovenia was performed. Inclusion criteria were:

The data were collected from the Cancer Registry, Slovenia, databases of Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Slovenia and Institute of Oncology Ljubljana, Slovenia.

Figure 1

Included patients were analysed for the gender, age, symptoms at presentation, date of cancer diagnosis, ICD-10 diagnosis, histology, clinical and pathological TNM stage (utilising the University of Pittsburgh TNM staging system (Table 1) for EACC and MEC or 8th edition of UICC staging system for aEEC and aPC), tumour localisation according to the abovementioned classification, preoperative head and neck imaging modalities and preoperative pure tone audiometry. Pure tone average was calculated for the affected ear (for bone and air conduction) as an average of hearing levels of pure tone audiometry at speech frequencies (i.e., 500 Hz, 1000 Hz, 1500 Hz, 2000 Hz, 3000 Hz and 4000 Hz). The average air-bone gap was calculated from pure tone average for bone and air conduction.

Moreover, date of surgery, treatment modalities employed (i.e., surgery, radiotherapy, systemic therapy), residual tumour classification according to the UICC staging system (i.e., R0 no residual tumour, R1 microscopic residual tumour and R2 macroscopic residual tumour), and date of the last recorded check-up or date and reason of death were analysed. Cancer recurrence was defined as the re-appearance of cancer in the surgical bed after the treatment was completed, and cancer was considered cured.

Listed data was used to analyse age at the cancer diagnosis, age at death, postoperative follow-up period and survival. Local control and overall survival crude rates and estimates using the Kaplan-Meier method were determined. Patients were considered cancer-free if there was no cancer recorded at five years after the surgery.

Statistical analysis was performed using Microsoft Excel for Mac (version 16 and later, Microsoft Corporation, Redmond, Washington) and SPSS (version 23, IBM Corp., Armonk, New York). Basic descriptive statistics were reported with means (M) and standard deviations (SD) and a p-value (p) below 0.05 was considered statistically significant.

Data collection was cut off on September 14^th, 2020. Initially, 177 patients were included in the study. Seventeen (10%) patients with lateral skull-base cancer were treated with curative intent between 2011 and 2019, and in 12 of them, the tumour was locally advanced (Table 2).

At the admission, 12 (71%) patients reported discharge, 10 (59%) crusting or nonhealing lesion, 10 (59%) pain, 6 (35%) bleeding, 5 (29%) hearing loss and 2 (12%) itching. A patient (6%) with aPC extending to the lateral skull-base reported the unilateral facial muscle weakness. None reported vertigo or other symptoms related to other cranial nerves involvement.

There was no left to right predominance (53% left and 47% right). Seven patients (41%) had an aEEC. Basal cell carcinoma was present in four (57%) and squamous cell carcinoma in three (43%) patients (Table 2).

Six patients (35%) suffered from EACC. The latter was classified as C44.2 in 100%. The cancer was squamous cell carcinoma in three (50%), basal cell carcinoma in two (33%) and adenoid cystic carcinoma in one patient (17%).

Figure 2

Both (12%) MECs were squamous cell carcinoma and two (12%) aPCs were mucoepidermoid carcinoma (50%) and adenocarcinoma (50%).

Disregarding the tumour localisation squamous cell carcinoma was the most common type (8 patients, 47%), followed by basal cell carcinoma (6 patients, 35%), and others (adenoid cystic carcinoma (6%), mucoepidermoid carcinoma (6%) and adenocarcinoma (6%).

In twelve patients (71%), the tumour was locoregionally advanced (i.e., grades III and IV). Preoperative skull-base imaging (i.e., CT or MRI) was performed in all of them. Pure tone average for air and bone conduction and air-bone gap could be calculated in eight patients (67%). Average value of pure tone average was 69 dB (SD = 39 dB) for air conduction, 43 dB (SD = 19 dB) for bone conduction and average air-bone gap was 26 dB (SD = 20 dB).

The primary surgery was the only treatment modality in five patients (42%) patients. Other treatment modalities employed were salvage surgery in three (25%) patients (i.e., one after radiotherapy, one after radiotherapy and electrochemotherapy, one after surgery and radiotherapy) and postoperative radiotherapy in four patients (33%) (Table 2). None received postoperative chemotherapy.

Wide local excision only was performed in two (16.7%), mastoidectomy in one (8.3%) and lateral temporal bone resection with obliteration in nine patients (75%). Additional partial parotidectomy was performed in six (50%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection of regions II–IV in eight (66.7%) and ipsilateral modified radical neck dissection including resection of the sternocleidomastoid muscle in one patient (8.3%).

The post-resection lateral skull-base defect was reconstructed with primary closure in five (41.7%) and flap in six (50%) patients with locoregionally advanced cancer. The wound was left to heal by secondary intention in one (8.3%) patient with T1N1M0 (stage III) EACC.

Reconstruction with ALT (Figure 3), RFFF (Figure 4) and PM (Figure 5) was performed in two patients each. There was no flap failure. In five patients (83%) with flap reconstruction, the resection was R0. Postoperative photon radiotherapy with a dose of 60 Gy and 64 Gy in 2 Gy daily fractions was performed in two patients, including the one with R1 resection.

The mean follow-up time (i.e., the mean overall survival time) of twelve patients after locoregion ally advanced lateral skull-base cancer resection was 2.9 years (SD = 2.6 years, range: 0.3 years – 8.1 years). At the data collection cut-off date, ten of these patients (83%) were alive and had no cancer recurrence (Table 2) (Figure 6A). Two patients (27%) died, but no recurrence was detected. One patient died with MEC since the resection was R1, and the patient did not receive planned postoperative radiotherapy due to generalised weakness. One patient after R0 resection of MEC died due to comorbidities. The survival was 100% in patients treated with flap reconstruction and 67% in patients treated with other reconstruction modalities (Figure 6B).

Figure 3

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Figure 5