Original Research—Head and Neck Surgery
Craniofacial Resection for T4 Maxillary Sinus Carcinoma: Managing Cases with Involvement of the Skull Base
Otolaryngology– Head and Neck Surgery 2015, Vol. 153(2) 231–238 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815586770 http://otojournal.org
Naoki Nishio, MD, PhD1*, Yasushi Fujimoto, MD, PhD1*, Masazumi Fujii, MD, PhD2, Kiyoshi Saito, MD, PhD3, Mariko Hiramatsu, MD, PhD1, Takashi Maruo, MD, PhD1, Kenichiro Iwami, MD, PhD3, Yuzuru Kamei, MD, PhD4, Shunjiro Yagi, MD, PhD4, Masakatsu Takahashi, MD, PhD5, Yuichiro Hayashi, PhD6, Atsushi Ando, MD7, and Tsutomu Nakashima, MD, PhD1
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. Study Design. Case series with chart review. Setting. Tertiary university hospital. Subjects and Methods. We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. Results. Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and diseasefree survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. Conclusion. This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates. Keywords craniofacial resection, maxillary sinus carcinoma, cavernous sinus, skull base, surgical strategy
Received December 15, 2014; revised April 1, 2015; accepted April 14, 2015.
Introduction Malignant tumors of the nasal cavity and paranasal sinuses are uncommon, comprising 0.2% to 0.5% of all cancer cases and accounting for only 3% of malignant tumors in the head and neck.1 Based on data from the Surveillance, Epidemiology, and End Results (SEER) database for all sinonasal malignancies reported between 1973 and 2006, the overall incidence of sinonasal cancer was 0.556 cases per 100,000 population per year, whereas the most common primary sites were the nasal cavity (43.9%) and maxillary sinus (35.9%).2 Based on data from the Report of Head and Neck Cancer Registry of Japan Clinical Statistics of Registered Patients in 2002, the most common primary sites were the maxillary sinus (71.3%) and nasal cavity (14.9%), and maxillary sinus carcinoma (MSC) was more frequent in Japan than in the United States. 1 Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 3 Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan 4 Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 5 Department of Otorhinolaryngology, Kariya General Hospital, Aichi, Japan 6 Information & Communications, Nagoya University, Nagoya, Japan 7 Department of Otorhinolaryngology, Japan Labor Health, and Welfare, Chubu Rosai Hospital, Nagoya, Japan * These two authors contributed equally to this work.
Corresponding Author: Naoki Nishio, MD, PhD, Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: [email protected]
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Maxillary sinus carcinoma is well known to often show few if any symptoms, thus increasing the likelihood of delayed diagnosis.3 Although MSC often involves surrounding tissues such as the orbit, nasal cavity, hard palate, skin, and skull base, the incidence of cervical lymph node metastasis is reported to be 10% to 20%.4,5 Multiple therapeutic treatments have been proposed for locally advanced MSC. Treatment of MSC is always difficult, given the combination of functional and cosmetic aspects. Based on responses to the Short Form-36 questionnaire, an internationally recognized ‘‘global’’ measure of quality of life comprising 36 items in 8 domains, patients with MSC experience lower quality of life not only in relation to physical factors but also in terms of mental factors.6-8 Although surgical resection of the maxillary sinuses might result in significant functional and aesthetic problems,9,10 several studies have reported that a combination of surgery (including craniofacial resection), radiotherapy, and/or chemotherapy offers better local control than radiotherapy alone.3,11 Most authorities agree that if possible, wide en bloc resection of the tumor with free margins is the most important goal. Although craniofacial resection is increasingly safe, thanks to the development of procedures such as reconstructive free flap, several limitations are encountered in resecting these tumors in an en bloc fashion, such as involvement of the nasopharynx, internal carotid artery, clivus, sphenoid sinus, and cavernous sinus. Saito et al12 developed 3 types of surgical procedure for manipulating the cavernous sinus to achieve en bloc resection for malignant tumors of the skull base. Using these surgical procedures, total excision of the locally advanced MSC can be achieved even if the tumor is impinging on the orbital apex, anterior cranial fossa, middle cranial fossa, and dura mater.12 Many authors have recently reported the results of craniofacial resection for several tumors of the skull base, showing good prognoses and low rates of complications. However, those reports have generally described benign or malignant tumors such as meningioma, chordoma, sarcoma, olfactory neuroblastoma, and carcinoma, and few reports have concerned the prognosis or complications of craniofacial resection for locally advanced MSC. The aim of this study was to identify the clinical and histological features and treatment results of en bloc craniofacial resection for locally advanced MSC classified as T4 and to clarify methods for treating cases with involvement of the skull base.
Methods Characteristics Participants in this study comprised 40 patients with locally advanced MSC in stage T4 who underwent anterolateral craniofacial resection in the Department of Otorhinolaryngology at Nagoya University Hospital between 1992 and 2011. We retrospectively analyzed clinical and pathological characteristics such as operative data, overall survival (OS), disease-free survival (DFS), and complications for patients with locally
advanced MSC. Tumor stage was determined using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US), and TNM stage was reclassified using the American Joint Committee on Cancer seventh edition criteria. Patients who had previously been treated at another hospital with procedures such as total maxillectomy, partial maxillectomy, concurrent chemoradiotherapy (CCRT), superselective intra-arterial chemotherapy, and heavy ion therapy were included in this study as recurrent cases after previous therapy. Complications were considered if occurring within 30 days postoperatively and were categorized into 3 groups: central nervous system (CNS) complications, wound complications, and systemic complications. Cerebrospinal fluid (CSF) leakage was classified as major if it lasted more than 1 week or required any operative intervention. The major wound complications were loss of all or part of the flap used in reconstruction and the need for surgical treatment. This study was approved by the ethics review committee of Nagoya University Hospital.
Treatment Strategy Since 1992, we have performed anterolateral craniofacial resection in an en bloc fashion for locally advanced MSC at stage T4. By evaluating the lymph nodes using CT, MRI, and US, we performed therapeutic neck dissection for N1-3 disease and no elective neck dissection for N0 disease. We have not performed this operation for patients with involvement of the sphenoidal sinus or clivus; with distant metastases of the carcinoma to areas such as bone, lungs, and liver; with general condition insufficient to allow craniofacial resection (ie, worse than performance status 2 as defined by the Eastern Cooperative Oncology Group)13; or who declined to undergo surgical resection. Head and neck surgeons performed neck dissection, if N1-3, and continued facial dissection with a WeberFergusson incision. Next, neurosurgeons used an anterolateral craniofacial approach, and the greater wing of the sphenoid and root of the pterygoid process were resected in all cases. The tumor was then resected en bloc. After resection of the tumor, plastic surgeons reconstructed the defect of the cranial base using a rectus abdominis myocutaneous free flap, sometimes with a temporoparietal galeal flap. Table 1 shows our surgical strategy for locally advanced maxillary carcinoma at stage T4. Because of the difficulty with achieving en bloc resection, cases with involvement of the sphenoid sinus or clivus have not been indicated for surgical resection. For management of the cavernous sinus, we performed treatment using the resection methods described by Saito et al12 using 3 types of resection. In a type 1 procedure, the cavernous sinus was dissected epidurally and retracted posteriorly. In a type 2 procedure, the anterolateral portion of the cavernous sinus was excised and the carotid artery preserved. In a type 3 procedure, the entire cavernous sinus was resected, including the carotid artery. Since 1992, we have resected locally advanced MSC in an en bloc fashion. In the early period (1992-1997), we treated cases with total involvement of the cavernous sinus by performing a
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Table 1. Our Surgical Strategy for T4 Maxillary Sinus Carcinoma.a
Table 2. Characteristics of Cases.
T Stage
Characteristics
4a
4b
Front of the orbit Buccal skin Pterygoid process Infratemporal fossa Cribriform lamina Frontal sinus Sphenoidal sinus Orbital apex Dura mater or brain Middle parts of skull With invasion to lateral wall of CS First period (1992-1997) Second period (1998-2011) With total involvement of CS First period (1992-1997) Second period (1998-2011) Nasopharynx Clivus
Treatment CFR with type 1
Inoperable CFR with type 1 or 2 CFR with type 1 or 2b CFR with type 1 CFR with type 2 Inoperable CFR with type 3c Inoperable CFR with type 1 Inoperable
Abbreviations: CFR, craniofacial resection; CS, cavernous sinus. a Type 1: cavernous sinus was dissected epidurally and retracted posteriorly. Type 2: anterolateral portion of the cavernous sinus was excised and the carotid artery preserved. Type 3: entire cavernous sinus including carotid artery was resected. b Depending on brain involvement. c Sometimes with high-flow bypass.
type 3 procedure with high-flow bypass, while cases with invasion to the lateral wall of the cavernous sinus were treated using a type 2 procedure. In consideration of the severe complications encountered during the perioperative period and the poor prognosis resulting from craniofacial resection, cases with involvement of the cavernous sinus have not been indicated for surgical resection since 1998. In cases showing positive margins, we added radiotherapy as a postoperative treatment. Since 2005, we have advocated postoperative radiotherapy for all cases, after encountering several local recurrences even in cases showing negative margins. Adjuvant radiotherapy was then started within 6 weeks postoperatively. The surgical bed is planned to receive 40 to 60 Gy, in 2-Gy fractions at 5 fractions per week. As adjuvant chemotherapy, we have administered cisplatinbased chemoradiotherapy for cases with positive margins or extranodal spread.
Analysis Statistical analysis was performed using JMP version 10 software (SAS, Cary, North Carolina, USA). Overall survival and DFS were estimated using the Kaplan-Meier method, and differences in survival rate were estimated using the log-rank test. Overall survival was calculated from the first visit to the date of death or last follow-up. Diseasefree survival was calculated from the first visit to the date of recurrence or last follow-up.
Total Cases Age, y Mean (range) 60 \60 Sex Male Female T classification T4a T4b N classification N0 N1 N2a N2b Stage grouping IVa IVb Tumor histology Squamous cell carcinoma Adenoid cystic carcinoma Adenocarcinoma Mucoepidermoid carcinoma Myoepithelial carcinoma Undifferentiated carcinoma Traditional carcinoma
n (%) 40 (100) 58.1 (43-75) 19 (47.5) 21 (52.5) 29 (72.5) 11 (27.5) 26 (65.0) 14 (35.0) 35 3 1 1
(87.5) (7.5) (2.5) (2.5)
26 (65.0) 14 (35.0) 32 2 2 1 1 1 1
(80.0) (5.0) (5.0) (2.5) (2.5) (2.5) (2.5)
Results Case Characteristics Table 2 shows the characteristics and histological diagnoses for the 40 cases. Median duration of follow-up was 40 months (range, 1-158 months). Patients comprised 29 men and 11 women with a mean age at the time of surgery of 58.1 years (range, 43-75 years). The T classification was T4a in 26 patients and T4b in 14, and 5 cases with cavernous sinus involvement were included. Histological diagnosis was squamous cell carcinoma (SCC) in 32 patients, adenocarcinoma in 2, adenoid cystic carcinoma in 2, mucoepidermoid carcinoma in 1, myoepithelial carcinoma in 1, undifferentiated carcinoma in 1, and transitional carcinoma in 1. Table 3 shows the disease condition for the 40 patients. Thirty patients presented with previously untreated primary tumors. Before craniofacial resection, 6 patients received no prior treatment, 6 received radiotherapy, 10 received chemotherapy with cisplatin and 5-fluorouracil and/or docetaxel, and 8 received both radiotherapy and chemotherapy. Ten cases involved recurrences after previous therapy, including 6 cases with previous total maxillectomy and 2 cases with a history of heavy-ion therapy.
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Table 3. Underlying Diseases in Cases. Treatment Characteristics Cases Previously untreated tumor Prior treatment in untreated tumor No treatment RT CT CCRT Reccurrent tumor Previous treatment in recurrent tumor Total maxillectomy 1 RT CCRT (including heavy-ion therapy)
Table 4. Complications. n (%) 40 (100) 30 (75.0) 6 6 10 8 10
(15.0) (15.0) (25.0) (20.0) (25.0)
6 (15.0) 4 (10.0)
Abbreviations: CCRT, concurrent chemoradiotherapy; CT, chemotherapy; RT, radiotherapy.
For all 40 cases, mean operation time was 942 minutes (range, 616-1945 min), and the mean amount of intraoperative blood loss was 1426 ml (range, 500-6228 ml). The 40 cases included 31 (77.5%) with negative margins and 9 (22.5%) with positive margins.
Type of Complications
n (%)
Cases Mortality rate Complications Central nervous system Cerebral infarction CSF leakage major CSF leakage minor Meningitis Pseudoaneurysm of OA Hydrocephalus Pneumocephalus Wound Major Minor Systemic Pneumonia
40 (100) 2 (5.0) 24 (60.0) 15 (37.5) 4 (10.0) 4 (10.0) 3 (7.5) 2 (5.0) 2 (5.0) 1 (2.5) 1 (2.5) 9 (22.5) 5 (12.5) 4 (10.0) 3 (7.5) 3 (7.5)
Abbreviations: CSF, cerebrospinal fluid leakage; OA, ophthalmic artery.
1.0
Complications Table 4 shows the complications encountered after craniofacial resection for T4 MSC. The mortality rate for the 40 cases was 5.0%. Twenty-four cases (60.0%) developed surgical complications after craniofacial resection. Fifteen cases (37.5%) suffered CNS complications, such as cerebral infarction, meningitis, CSF leakage, and pseudoaneurysm of the ophthalmic artery. We encountered severe CNS complications in all 5 cases with cavernous sinus involvement. Excluding these 5 cases, 10 cases showed CNS complications, 1 patient died within 30 days because of severe cerebral infarction, and 1 patient left the hospital with hemiparesis. Another 2 patients developed pseudoaneurysm of the ophthalmic artery. One case was detected by following contrast-enhanced CT and was treated by intra-arterial occlusion, and the other case led to rupture of the aneurysm and epidural hemorrhage and cerebral infarction. Wound complications developed in 9 cases (22.5%), comprising major complications in 5 cases and minor complications in 4 cases. One of the 2 patients who had previously undergone heavy-ion therapy suffered local necrosis. After postoperative day 26, we removed the necrotic bone tissue within the area of heavy-ion therapy.
Recurrence Seventeen of the 40 patients (42.5%) experienced tumor recurrence, with local recurrence in 7 cases (17.5%), local and neck recurrence in 2 cases (5%), and only neck recurrence in 1 case (2.5%). Four patients (10%) showed metastasis to the node of Rouviere, including 1 case with neck recurrence. Three cases (7.5%) presented with distant metastases as the sole site of recurrence.
0.8
OS
0.6
DFS
0.4
5-year OS = 62.7%
0.2
5-year DFS = 52.6% 0.0 0
12
24
36
48
60
Months Figure 1. Kaplan-Meier survival curves for overall survival (OS) and disease-free survival (DFS) in 40 cases.
Survival Rate In all 40 patients with locally advanced MSC at stage T4, the 5-year OS and DFS rates were 62.7% and 52.6%, respectively (Figure 1). In addition, we analyzed only 32 patients with SCC, showing 5-year OS and DFS rates of 51.3% and 48.1%, respectively. A significant difference was seen with involvement of the cavernous sinus. Five-year OS rate was significantly lower in patients with cavernous sinus involvement (20%) than in patients without such involvement (72.4%; P = .012) (Figure 2). In the 35 patients without cavernous sinus involvement, the 5-year OS and DFS rates were 72.4% and 55.3%, respectively. We stopped attempting resection of the involved cavernous sinus in 1998, so all data on resected cavernous sinus are from only
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1.0
Negative (n=26) CS free (n=35)
0.8
0.8 0.6
0.6
Positive (n=9)
CS involved (n=5) 0.4
0.4
0.2
0.2
p = 0.019
p = 0.012 0.0
0.0 0
12
24
36
48
60
0
12
Figure 2. Kaplan-Meier survival curves for overall survival (OS) in 40 cases with and without cavernous sinus (CS) involvement. Cavernous sinus involvement represents a significant negative prognostic factor (P = .012).
24
36
48
60
Months
Months
Figure 4. Kaplan-Meier survival curves for overall survival (OS) in 35 cases with negative or positive margins. Positive margins represent a significant negative prognostic factor (P = .019).
Cases with Involvement of the Cavernous Sinus Table 5 shows clinical data for the 5 cases with involvement of the cavernous sinus. Case 1 showed involvement of the cavernous sinus, dura mater, and brain and was treated using a type 3 procedure but suffered substantial bleeding. This patient died 7 days postoperatively because of severe cerebral infarction. Case 2 showed involvement of the cavernous sinus, dura mater, and brain and was treated using a type 3 procedure after creating a superficial temporal artery-middle cerebral artery bypass. He experienced severe cerebral infarction, then developed right hemiparesis and dysphagia.
1.0
Previously untreated tumor (n=28) 0.8 0.6
Recurrent tumor (n=7) 0.4 0.2
p = 0.017
Illustrative Case
0.0 0
12
24
36
48
60
Months Figure 3. Kaplan-Meier survival curves for overall survival (OS) in 35 cases with previously untreated or recurrent tumor. Recurrent tumor represents a significant negative prognostic factor (P = .017).
6 years of the total 19-year period. Given cavernous sinus involvement represents a poor prognostic factor, we excluded the 5 cases with cavernous sinus involvement from the following analysis. The 35 cases without cavernous sinus involvement showed significant differences in terms of previous treatment and surgical margins. Of the 35 patients, 28 had previously untreated primary tumors, and 7 cases had recurrent tumors. The 5-year OS rate was significantly lower in patients with recurrent tumors (42.9%) than in those with previously untreated tumors (80.6%; P = .017) (Figure 3). Of the 35 patients, 26 showed negative tumor margins, while 9 showed positive margins. The 5-year OS rate was significantly lower in cases with positive margins (45.0%) than in cases displaying negative margins (79.7%; P = .019) (Figure 4).
A 52-year-old man presented with a 1-month history of nasal bleeding and left cheek swelling. The MRI showed a mass lesion in the left maxillary sinus involving the infratemporal fossa (Figure 5A).We diagnosed the locally advanced MSC as myoepithelial carcinoma, T4aN0M0. After radiotherapy, we chose to approach the tumor by craniofacial resection including removal of the left eye. First, using Weber-Fergusson incision, head and neck surgeons dissected the left face and cut the coronoid process of the mandible and zygomatic arch. Left fronto-temporal craniotomy was performed, and the anterior cranial base was exposed epidurally. The cavernous sinus was dissected epidurally and retracted posteriorly. An osteotomy was made in the anterior cranial base at the sphenoid body anterior to the foramen ovale. After cutting the hard palate and sphenoid floor, the tumor was resected en bloc (Figure 5B). Antero-middle skull base reconstruction was then performed by plastic surgeons using a rectus abdominis myocutaneous free flap and temporal fascia (Figure 5C). At 10 days after the operation, he presented with CSF leakage and resolved after bedrest in a semi-sitting position for 1 week. At 40 days after the operation, he left the hospital with no prognostic symptom. Follow-up examination and MRI after 2 years have shown no recurrent tumor (Figure 5D).
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Table 5. Cases with CS Involvement. Case Age Sex T Tumor Histology
Tumor
Management of CS
Outcome
Follow-up, d Recurrent Area
1 2 3
57 44 63
M 4b M 4b M 4b
SCC ACC SCC
Untreated Recurrent Recurrent
Type 3 Type 3 Type 2
Died Disease-free Died
7 4011 470
4 5
58 60
M 4b M 4b
SCC SCC
Untreated Recurrent
Type 2 Type 2
Died Died
1776 173
Complications
None None Local
Cerebral infarction Cerebral infarction Cerebral infarction, meningitis, pneumonia Distant Hydrocephalus Local and neck CSF leakage major
Abbreviations: ACC, adenoid cystic carcinoma; CS, cavernous sinus; CSF, cerebrospinal fluid leakage; SCC, squamous cell carcinoma.
Figure 5. (A) Preoperative T2-weighted magnetic resonance imaging (MRI). (B) Intraoperative picture after craniofacial resection. (C) Intraoperative picture after reconstruction. (D) Follow-up T2-weighted MRI.
Discussion When Ketcham et al14 first reported craniofacial resection for sinonasal carcinoma in 1963, craniofacial resection would occasionally lead to severe complications and was a challenging operation. Many recent studies have described good results for craniofacial resection of malignant skull base tumors.12,15-18 An international collaborative study showed a 5-year OS rate of 54% for malignant skull base tumors.19 Survival of patients with sinonasal malignancy has previously been studied, reporting a 5-year OS rate of 40% for all malignancies and 60% for sinonasal squamous cell carcinoma specifically.3,20 This study only included cases of locally advanced MSC classified as T4, finding a 5-year OS rate of 62.7% and, more particularly, a 5-year OS rate of 72.4% without cavernous sinus involvement. Considering the advanced stage, our outcomes were relatively favorable.
In the early period, we encountered severe CNS complications such as internal carotid artery occlusion, cerebral infarction, and meningitis, in all cases showing involvement of the cavernous sinus. Because all cases with involvement of the cavernous sinus experienced severe CNS complications, our data for CNS complications were worse than those of the international collaborative study. Although we performed excision of locally advanced MSC with involvement of the cavernous sinus in en bloc fashion using high-flow bypass in the early period of our experience, the severe perioperative complications encountered and poor postoperative prognosis led us to reconsider the surgical indications. After we stopped conducting craniofacial resection for cases with involvement of the cavernous sinus, the rate of severe CNS complications decreased, and the overall complication rate became acceptable. Medical comorbidity, prior radiation therapy, elderly patients (70 years old), and
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the extent of intracranial tumor involvement were independent predictors of postoperative complications.18,21,22 To perform accurate osteotomy around the cavernous sinus, we conducted surgical methods aimed at managing the cavernous sinus in en bloc resections of malignant skull base tumors as reported by Saito et al12 and performed craniofacial resection even if the T stage was T4b, such as with involvement of the cavernous sinus and orbital apex. By conducting the type 1 procedure for patients with involvement of the orbital apex, we can remove the tumor in an en bloc fashion completely and safely. Although technically possible, adding carotid resection to the surgical procedures increases the risk of postoperative cerebral infarction.12 Because of the severe complications in the early period and early recurrences after surgery, we are no longer performing surgical resection for patients with cavernous sinus involvement. Whether postoperative treatments such as radiotherapy and/or chemotherapy are needed after complete resection remains controversial. Outcomes after single-modality therapy are generally poor, so the postoperative period is generally considered the optimal timing for radiotherapy relative to surgery.3,23,24 Although little data are currently available regarding the efficiency of CCRT for locally advanced MSC,25 Kang et al26 reported that the combination of surgery, radiotherapy, and/or chemotherapy might be superior to CCRT for locally advanced MSC. Craniofacial resection could achieve good results for locally advanced MSC, but operative stress including excessive blood loss is never less and might lead to a fatal condition. Craniofacial resection is therefore not recommended to patients over 75 years old or with severe comorbidities. Focused on the functional and aesthetic problems, such as removal of an orbit, minimally invasive procedures have recently been reported. In well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal carcinoma results in acceptable oncologic outcomes.27,28 Superselective intra-arterial infusion of concomitant radiotherapy (RADPLAT) has been reported to result in favorable survival rates.29-31 Several papers have examined the efficiency of proton/heavy-ion therapy for managing locally advanced sinonasal malignancies.32-35 As radiotherapy, including CCRT, RADPLAT, and proton/heavy-ion therapy, becomes more popular, cases of recurrent MSC after radiotherapy therapy seem likely to increase in frequency. Few treatment options are available for patients with recurrent MSC after radiotherapy, so craniofacial resection in an en bloc fashion is set to play a more important role. This study was based on a relatively small and heterogeneous group of cases, from multiple perspectives: pathology, prior treatment, decisions about adjuvant treatment, treatment, and inclusion and exclusion criteria over the time period of the series. This represents a key weakness in our study, and the results need to be confirmed in a larger series of patients.
Conclusion The present study focused on locally advanced MSC with skull base involvement. With accurate osteotomy around the
cavernous sinus, we can remove the tumor in an en bloc fashion completely and safely. Even for cases of locally advanced MSC classified as T4, craniofacial resection in an en bloc fashion achieved a good survival rate. Author Contributions Naoki Nishio, data analysis, drafting, final approval, accountability for all aspects of the work; Yasushi Fujimoto, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Masazumi Fujii, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Kiyoshi Saito, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Mariko Hiramatsu, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Takashi Maruo, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Kenichiro Iwami, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Yuzuru Kamei, acquisition of data, design, revising critically for the area of plastic reconstructive surgery, final approval; Shunjiro Yagi, acquisition of data, design, revising critically for the area of plastic reconstructive surgery, final approval; Masakatsu Takahashi, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Yuichiro Hayashi, acquisition of data, design, revising critically for the area of navigation system, final approval; Atsushi Ando, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Tsutomu Nakashima, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval.
Disclosures Competing interests: None. Sponsorships: None. Funding source: National Cancer Center Research and Development Fund (23-A-26), JSPS Grant-in-Aid for Research Activity Start-up. Request for proof reading.
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8. McHorney CA, Ware JE, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993;31:247-263. 9. Alvarez I, Sua´rez C, Rodrigo JP, Nun˜ez F, Caminero MJ. Prognostic factors in paranasal sinus cancer. Am J Otolaryngol. 1995;16:109-114. 10. Harbo G, Grau C, Bundgaard T, et al. Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients. Acta Oncol. 1997;36:45-50. 11. Katz TS, Mendenhall WM, Morris CG, Amdur RJ, Hinerman RW, Villaret DB. Malignant tumors of the nasal cavity and paranasal sinuses. Head Neck. 2002;24:821-829. 12. Saito K, Fukuta K, Takahashi M, Tachibana E, Yoshida J. Management of the cavernous sinus in en bloc resections of malignant skull base tumors. Head Neck. 1999;21:734-742. 13. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655. 14. Ketcham AS, Wilkins RH, Vanburen JM, Smith RR. A combined intracranial facial approach to the paranasal sinuses. Am J Surg. 1963;106:698-703. 15. Shah JP, Sundaresan N, Galicich J, Strong EW. Craniofacial resections for tumors involving the base of the skull. Am J Surg. 1987;154:352-358. 16. Cantu G, Solero CL, Riccio S, et al. Surgery for malignant maxillary tumors involving the middle cranial fossa. Skull Base. 2010;20:55-60. 17. Bilsky MH, Bentz B, Vitaz T, Shah J, Kraus D. Craniofacial resection for cranial base malignancies involving the infratemporal fossa. Neurosurgery. 2005;57(suppl 4):339-347. 18. Sakashita T, Oridate N, Homma A, et al. Complications of skull base surgery: an analysis of 30 cases. Skull Base. 2009; 19:127-132. 19. Patel SG, Singh B, Polluri A, et al. Craniofacial surgery for malignant skull base tumors: report of an international collaborative study. Cancer. 2003;98:1179-1187. 20. Sanghvi S, Khan MN, Patel NR, Yeldandi S, Baredes S, Eloy JA. Epidemiology of sinonasal squamous cell carcinoma: a comprehensive analysis of 4,994 patients. Laryngoscope. 2013;124:76-83. 21. Ganly I, Patel SG, Singh B, et al. Complications of craniofacial resection for malignant tumors of the skull base: report of an international collaborative study. Head Neck. 2005;27:445-451. 22. Ganly I, Patel SG, Singh B, et al. Craniofacial resection for malignant tumors involving the skull base in the elderly: an international collaborative study. Cancer. 2011;117:563-571. 23. Jiang GL, Ang KK, Peters LJ, Wendt CD, Oswald MJ, Goepfert H. MSCs: natural history and results of postoperative radiotherapy. Radiother Oncol. 1991;21:193-200.
24. Duthoy W, Boterberg T, Claus F, et al. Postoperative intensity-modulated radiotherapy in sinonasal carcinoma: clinical results in 39 patients. Cancer. 2005;104:71-82. 25. Nishimura G, Tsukuda M, Mikami Y, et al. The efficacy and safety of concurrent chemoradiotherapy for maxillary sinus squamous cell carcinoma patients. Auris Nasus Larynx. 2009;36:547-554. 26. Kang JH, Cho SH, Pyeong-Kim J, et al. Treatment outcomes between concurrent chemoradiotherapy and combination of surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus cancer: multi-institutional retrospective analysis. J Oral Maxillofac Surg. 2012;70:1717-1723. 27. Hanna E, DeMonte F, Ibrahim S, Roberts D, Levine N, Kupferman M. Endoscopic resection of sinonasal cancers with and without craniotomy: oncologic results. Arch Otolaryngol Head Neck Surg. 2009;135:1219-1224. 28. Nicolai P, Battaglia P, Bignami M, et al. Endoscopic surgery for malignant tumors of the sinonasal tract and adjacent skull base: a 10-year experience. Am J Rhinol. 2008;22:308-316. 29. Samant S, Robbins KT, Vang M, Wan J, Robertson J. Intraarterial cisplatin and concomitant radiation therapy followed by surgery for advanced paranasal sinus cancer. Arch Otolaryngol Head Neck Surg. 2004;130:948-955. 30. Shiga K, Yokoyama J, Hashimoto S, et al. Combined therapy after superselective arterial cisplatin infusion to treat maxillary squamous cell carcinoma. Otolaryngol Head Neck Surg. 2007; 136:1003-1009. 31. Homma A, Oridate N, Suzuki F, et al. Superselective high-dose cisplatin infusion with concomitant radiotherapy in patients with advanced cancer of the nasal cavity and paranasal sinuses: a single institution experience. Cancer. 2009;115:4705-4714. 32. Mock U, Georg D, Bogner J, Auberger T, Po¨tter R. Treatment planning comparison of conventional, 3D conformal, and intensity-modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma. Int J Radiat Oncol Biol Phys. 2004;58:147-154. 33. Weber DC, Chan AW, Lessell S, et al. Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons. Radiother Oncol. 2006;81:243-249. 34. Fukumitsu N, Okumura T, Mizumoto M, et al. Outcome of T4 (International Union Against Cancer Staging System, 7th edition) or recurrent nasal cavity and paranasal sinus carcinoma treated with proton beam. Int J Radiat Oncol Biol Phys. 2012; 83:704-711. 35. Resto VA, Chan AW, Deschler DG, Lin DT. Extent of surgery in the management of locally advanced sinonasal malignancies. Head Neck. 2008;30:222-229.
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Craniofacial Resection for T4 Maxillary Sinus Carcinoma: Managing Cases with Involvement of the Skull Base
Otolaryngology– Head and Neck Surgery 2015, Vol. 153(2) 231–238 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815586770 http://otojournal.org
Naoki Nishio, MD, PhD1*, Yasushi Fujimoto, MD, PhD1*, Masazumi Fujii, MD, PhD2, Kiyoshi Saito, MD, PhD3, Mariko Hiramatsu, MD, PhD1, Takashi Maruo, MD, PhD1, Kenichiro Iwami, MD, PhD3, Yuzuru Kamei, MD, PhD4, Shunjiro Yagi, MD, PhD4, Masakatsu Takahashi, MD, PhD5, Yuichiro Hayashi, PhD6, Atsushi Ando, MD7, and Tsutomu Nakashima, MD, PhD1
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. Study Design. Case series with chart review. Setting. Tertiary university hospital. Subjects and Methods. We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. Results. Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and diseasefree survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. Conclusion. This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates. Keywords craniofacial resection, maxillary sinus carcinoma, cavernous sinus, skull base, surgical strategy
Received December 15, 2014; revised April 1, 2015; accepted April 14, 2015.
Introduction Malignant tumors of the nasal cavity and paranasal sinuses are uncommon, comprising 0.2% to 0.5% of all cancer cases and accounting for only 3% of malignant tumors in the head and neck.1 Based on data from the Surveillance, Epidemiology, and End Results (SEER) database for all sinonasal malignancies reported between 1973 and 2006, the overall incidence of sinonasal cancer was 0.556 cases per 100,000 population per year, whereas the most common primary sites were the nasal cavity (43.9%) and maxillary sinus (35.9%).2 Based on data from the Report of Head and Neck Cancer Registry of Japan Clinical Statistics of Registered Patients in 2002, the most common primary sites were the maxillary sinus (71.3%) and nasal cavity (14.9%), and maxillary sinus carcinoma (MSC) was more frequent in Japan than in the United States. 1 Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 3 Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan 4 Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 5 Department of Otorhinolaryngology, Kariya General Hospital, Aichi, Japan 6 Information & Communications, Nagoya University, Nagoya, Japan 7 Department of Otorhinolaryngology, Japan Labor Health, and Welfare, Chubu Rosai Hospital, Nagoya, Japan * These two authors contributed equally to this work.
Corresponding Author: Naoki Nishio, MD, PhD, Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Email: [email protected]
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Maxillary sinus carcinoma is well known to often show few if any symptoms, thus increasing the likelihood of delayed diagnosis.3 Although MSC often involves surrounding tissues such as the orbit, nasal cavity, hard palate, skin, and skull base, the incidence of cervical lymph node metastasis is reported to be 10% to 20%.4,5 Multiple therapeutic treatments have been proposed for locally advanced MSC. Treatment of MSC is always difficult, given the combination of functional and cosmetic aspects. Based on responses to the Short Form-36 questionnaire, an internationally recognized ‘‘global’’ measure of quality of life comprising 36 items in 8 domains, patients with MSC experience lower quality of life not only in relation to physical factors but also in terms of mental factors.6-8 Although surgical resection of the maxillary sinuses might result in significant functional and aesthetic problems,9,10 several studies have reported that a combination of surgery (including craniofacial resection), radiotherapy, and/or chemotherapy offers better local control than radiotherapy alone.3,11 Most authorities agree that if possible, wide en bloc resection of the tumor with free margins is the most important goal. Although craniofacial resection is increasingly safe, thanks to the development of procedures such as reconstructive free flap, several limitations are encountered in resecting these tumors in an en bloc fashion, such as involvement of the nasopharynx, internal carotid artery, clivus, sphenoid sinus, and cavernous sinus. Saito et al12 developed 3 types of surgical procedure for manipulating the cavernous sinus to achieve en bloc resection for malignant tumors of the skull base. Using these surgical procedures, total excision of the locally advanced MSC can be achieved even if the tumor is impinging on the orbital apex, anterior cranial fossa, middle cranial fossa, and dura mater.12 Many authors have recently reported the results of craniofacial resection for several tumors of the skull base, showing good prognoses and low rates of complications. However, those reports have generally described benign or malignant tumors such as meningioma, chordoma, sarcoma, olfactory neuroblastoma, and carcinoma, and few reports have concerned the prognosis or complications of craniofacial resection for locally advanced MSC. The aim of this study was to identify the clinical and histological features and treatment results of en bloc craniofacial resection for locally advanced MSC classified as T4 and to clarify methods for treating cases with involvement of the skull base.
Methods Characteristics Participants in this study comprised 40 patients with locally advanced MSC in stage T4 who underwent anterolateral craniofacial resection in the Department of Otorhinolaryngology at Nagoya University Hospital between 1992 and 2011. We retrospectively analyzed clinical and pathological characteristics such as operative data, overall survival (OS), disease-free survival (DFS), and complications for patients with locally
advanced MSC. Tumor stage was determined using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US), and TNM stage was reclassified using the American Joint Committee on Cancer seventh edition criteria. Patients who had previously been treated at another hospital with procedures such as total maxillectomy, partial maxillectomy, concurrent chemoradiotherapy (CCRT), superselective intra-arterial chemotherapy, and heavy ion therapy were included in this study as recurrent cases after previous therapy. Complications were considered if occurring within 30 days postoperatively and were categorized into 3 groups: central nervous system (CNS) complications, wound complications, and systemic complications. Cerebrospinal fluid (CSF) leakage was classified as major if it lasted more than 1 week or required any operative intervention. The major wound complications were loss of all or part of the flap used in reconstruction and the need for surgical treatment. This study was approved by the ethics review committee of Nagoya University Hospital.
Treatment Strategy Since 1992, we have performed anterolateral craniofacial resection in an en bloc fashion for locally advanced MSC at stage T4. By evaluating the lymph nodes using CT, MRI, and US, we performed therapeutic neck dissection for N1-3 disease and no elective neck dissection for N0 disease. We have not performed this operation for patients with involvement of the sphenoidal sinus or clivus; with distant metastases of the carcinoma to areas such as bone, lungs, and liver; with general condition insufficient to allow craniofacial resection (ie, worse than performance status 2 as defined by the Eastern Cooperative Oncology Group)13; or who declined to undergo surgical resection. Head and neck surgeons performed neck dissection, if N1-3, and continued facial dissection with a WeberFergusson incision. Next, neurosurgeons used an anterolateral craniofacial approach, and the greater wing of the sphenoid and root of the pterygoid process were resected in all cases. The tumor was then resected en bloc. After resection of the tumor, plastic surgeons reconstructed the defect of the cranial base using a rectus abdominis myocutaneous free flap, sometimes with a temporoparietal galeal flap. Table 1 shows our surgical strategy for locally advanced maxillary carcinoma at stage T4. Because of the difficulty with achieving en bloc resection, cases with involvement of the sphenoid sinus or clivus have not been indicated for surgical resection. For management of the cavernous sinus, we performed treatment using the resection methods described by Saito et al12 using 3 types of resection. In a type 1 procedure, the cavernous sinus was dissected epidurally and retracted posteriorly. In a type 2 procedure, the anterolateral portion of the cavernous sinus was excised and the carotid artery preserved. In a type 3 procedure, the entire cavernous sinus was resected, including the carotid artery. Since 1992, we have resected locally advanced MSC in an en bloc fashion. In the early period (1992-1997), we treated cases with total involvement of the cavernous sinus by performing a
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Table 1. Our Surgical Strategy for T4 Maxillary Sinus Carcinoma.a
Table 2. Characteristics of Cases.
T Stage
Characteristics
4a
4b
Front of the orbit Buccal skin Pterygoid process Infratemporal fossa Cribriform lamina Frontal sinus Sphenoidal sinus Orbital apex Dura mater or brain Middle parts of skull With invasion to lateral wall of CS First period (1992-1997) Second period (1998-2011) With total involvement of CS First period (1992-1997) Second period (1998-2011) Nasopharynx Clivus
Treatment CFR with type 1
Inoperable CFR with type 1 or 2 CFR with type 1 or 2b CFR with type 1 CFR with type 2 Inoperable CFR with type 3c Inoperable CFR with type 1 Inoperable
Abbreviations: CFR, craniofacial resection; CS, cavernous sinus. a Type 1: cavernous sinus was dissected epidurally and retracted posteriorly. Type 2: anterolateral portion of the cavernous sinus was excised and the carotid artery preserved. Type 3: entire cavernous sinus including carotid artery was resected. b Depending on brain involvement. c Sometimes with high-flow bypass.
type 3 procedure with high-flow bypass, while cases with invasion to the lateral wall of the cavernous sinus were treated using a type 2 procedure. In consideration of the severe complications encountered during the perioperative period and the poor prognosis resulting from craniofacial resection, cases with involvement of the cavernous sinus have not been indicated for surgical resection since 1998. In cases showing positive margins, we added radiotherapy as a postoperative treatment. Since 2005, we have advocated postoperative radiotherapy for all cases, after encountering several local recurrences even in cases showing negative margins. Adjuvant radiotherapy was then started within 6 weeks postoperatively. The surgical bed is planned to receive 40 to 60 Gy, in 2-Gy fractions at 5 fractions per week. As adjuvant chemotherapy, we have administered cisplatinbased chemoradiotherapy for cases with positive margins or extranodal spread.
Analysis Statistical analysis was performed using JMP version 10 software (SAS, Cary, North Carolina, USA). Overall survival and DFS were estimated using the Kaplan-Meier method, and differences in survival rate were estimated using the log-rank test. Overall survival was calculated from the first visit to the date of death or last follow-up. Diseasefree survival was calculated from the first visit to the date of recurrence or last follow-up.
Total Cases Age, y Mean (range) 60 \60 Sex Male Female T classification T4a T4b N classification N0 N1 N2a N2b Stage grouping IVa IVb Tumor histology Squamous cell carcinoma Adenoid cystic carcinoma Adenocarcinoma Mucoepidermoid carcinoma Myoepithelial carcinoma Undifferentiated carcinoma Traditional carcinoma
n (%) 40 (100) 58.1 (43-75) 19 (47.5) 21 (52.5) 29 (72.5) 11 (27.5) 26 (65.0) 14 (35.0) 35 3 1 1
(87.5) (7.5) (2.5) (2.5)
26 (65.0) 14 (35.0) 32 2 2 1 1 1 1
(80.0) (5.0) (5.0) (2.5) (2.5) (2.5) (2.5)
Results Case Characteristics Table 2 shows the characteristics and histological diagnoses for the 40 cases. Median duration of follow-up was 40 months (range, 1-158 months). Patients comprised 29 men and 11 women with a mean age at the time of surgery of 58.1 years (range, 43-75 years). The T classification was T4a in 26 patients and T4b in 14, and 5 cases with cavernous sinus involvement were included. Histological diagnosis was squamous cell carcinoma (SCC) in 32 patients, adenocarcinoma in 2, adenoid cystic carcinoma in 2, mucoepidermoid carcinoma in 1, myoepithelial carcinoma in 1, undifferentiated carcinoma in 1, and transitional carcinoma in 1. Table 3 shows the disease condition for the 40 patients. Thirty patients presented with previously untreated primary tumors. Before craniofacial resection, 6 patients received no prior treatment, 6 received radiotherapy, 10 received chemotherapy with cisplatin and 5-fluorouracil and/or docetaxel, and 8 received both radiotherapy and chemotherapy. Ten cases involved recurrences after previous therapy, including 6 cases with previous total maxillectomy and 2 cases with a history of heavy-ion therapy.
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Table 3. Underlying Diseases in Cases. Treatment Characteristics Cases Previously untreated tumor Prior treatment in untreated tumor No treatment RT CT CCRT Reccurrent tumor Previous treatment in recurrent tumor Total maxillectomy 1 RT CCRT (including heavy-ion therapy)
Table 4. Complications. n (%) 40 (100) 30 (75.0) 6 6 10 8 10
(15.0) (15.0) (25.0) (20.0) (25.0)
6 (15.0) 4 (10.0)
Abbreviations: CCRT, concurrent chemoradiotherapy; CT, chemotherapy; RT, radiotherapy.
For all 40 cases, mean operation time was 942 minutes (range, 616-1945 min), and the mean amount of intraoperative blood loss was 1426 ml (range, 500-6228 ml). The 40 cases included 31 (77.5%) with negative margins and 9 (22.5%) with positive margins.
Type of Complications
n (%)
Cases Mortality rate Complications Central nervous system Cerebral infarction CSF leakage major CSF leakage minor Meningitis Pseudoaneurysm of OA Hydrocephalus Pneumocephalus Wound Major Minor Systemic Pneumonia
40 (100) 2 (5.0) 24 (60.0) 15 (37.5) 4 (10.0) 4 (10.0) 3 (7.5) 2 (5.0) 2 (5.0) 1 (2.5) 1 (2.5) 9 (22.5) 5 (12.5) 4 (10.0) 3 (7.5) 3 (7.5)
Abbreviations: CSF, cerebrospinal fluid leakage; OA, ophthalmic artery.
1.0
Complications Table 4 shows the complications encountered after craniofacial resection for T4 MSC. The mortality rate for the 40 cases was 5.0%. Twenty-four cases (60.0%) developed surgical complications after craniofacial resection. Fifteen cases (37.5%) suffered CNS complications, such as cerebral infarction, meningitis, CSF leakage, and pseudoaneurysm of the ophthalmic artery. We encountered severe CNS complications in all 5 cases with cavernous sinus involvement. Excluding these 5 cases, 10 cases showed CNS complications, 1 patient died within 30 days because of severe cerebral infarction, and 1 patient left the hospital with hemiparesis. Another 2 patients developed pseudoaneurysm of the ophthalmic artery. One case was detected by following contrast-enhanced CT and was treated by intra-arterial occlusion, and the other case led to rupture of the aneurysm and epidural hemorrhage and cerebral infarction. Wound complications developed in 9 cases (22.5%), comprising major complications in 5 cases and minor complications in 4 cases. One of the 2 patients who had previously undergone heavy-ion therapy suffered local necrosis. After postoperative day 26, we removed the necrotic bone tissue within the area of heavy-ion therapy.
Recurrence Seventeen of the 40 patients (42.5%) experienced tumor recurrence, with local recurrence in 7 cases (17.5%), local and neck recurrence in 2 cases (5%), and only neck recurrence in 1 case (2.5%). Four patients (10%) showed metastasis to the node of Rouviere, including 1 case with neck recurrence. Three cases (7.5%) presented with distant metastases as the sole site of recurrence.
0.8
OS
0.6
DFS
0.4
5-year OS = 62.7%
0.2
5-year DFS = 52.6% 0.0 0
12
24
36
48
60
Months Figure 1. Kaplan-Meier survival curves for overall survival (OS) and disease-free survival (DFS) in 40 cases.
Survival Rate In all 40 patients with locally advanced MSC at stage T4, the 5-year OS and DFS rates were 62.7% and 52.6%, respectively (Figure 1). In addition, we analyzed only 32 patients with SCC, showing 5-year OS and DFS rates of 51.3% and 48.1%, respectively. A significant difference was seen with involvement of the cavernous sinus. Five-year OS rate was significantly lower in patients with cavernous sinus involvement (20%) than in patients without such involvement (72.4%; P = .012) (Figure 2). In the 35 patients without cavernous sinus involvement, the 5-year OS and DFS rates were 72.4% and 55.3%, respectively. We stopped attempting resection of the involved cavernous sinus in 1998, so all data on resected cavernous sinus are from only
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1.0
Negative (n=26) CS free (n=35)
0.8
0.8 0.6
0.6
Positive (n=9)
CS involved (n=5) 0.4
0.4
0.2
0.2
p = 0.019
p = 0.012 0.0
0.0 0
12
24
36
48
60
0
12
Figure 2. Kaplan-Meier survival curves for overall survival (OS) in 40 cases with and without cavernous sinus (CS) involvement. Cavernous sinus involvement represents a significant negative prognostic factor (P = .012).
24
36
48
60
Months
Months
Figure 4. Kaplan-Meier survival curves for overall survival (OS) in 35 cases with negative or positive margins. Positive margins represent a significant negative prognostic factor (P = .019).
Cases with Involvement of the Cavernous Sinus Table 5 shows clinical data for the 5 cases with involvement of the cavernous sinus. Case 1 showed involvement of the cavernous sinus, dura mater, and brain and was treated using a type 3 procedure but suffered substantial bleeding. This patient died 7 days postoperatively because of severe cerebral infarction. Case 2 showed involvement of the cavernous sinus, dura mater, and brain and was treated using a type 3 procedure after creating a superficial temporal artery-middle cerebral artery bypass. He experienced severe cerebral infarction, then developed right hemiparesis and dysphagia.
1.0
Previously untreated tumor (n=28) 0.8 0.6
Recurrent tumor (n=7) 0.4 0.2
p = 0.017
Illustrative Case
0.0 0
12
24
36
48
60
Months Figure 3. Kaplan-Meier survival curves for overall survival (OS) in 35 cases with previously untreated or recurrent tumor. Recurrent tumor represents a significant negative prognostic factor (P = .017).
6 years of the total 19-year period. Given cavernous sinus involvement represents a poor prognostic factor, we excluded the 5 cases with cavernous sinus involvement from the following analysis. The 35 cases without cavernous sinus involvement showed significant differences in terms of previous treatment and surgical margins. Of the 35 patients, 28 had previously untreated primary tumors, and 7 cases had recurrent tumors. The 5-year OS rate was significantly lower in patients with recurrent tumors (42.9%) than in those with previously untreated tumors (80.6%; P = .017) (Figure 3). Of the 35 patients, 26 showed negative tumor margins, while 9 showed positive margins. The 5-year OS rate was significantly lower in cases with positive margins (45.0%) than in cases displaying negative margins (79.7%; P = .019) (Figure 4).
A 52-year-old man presented with a 1-month history of nasal bleeding and left cheek swelling. The MRI showed a mass lesion in the left maxillary sinus involving the infratemporal fossa (Figure 5A).We diagnosed the locally advanced MSC as myoepithelial carcinoma, T4aN0M0. After radiotherapy, we chose to approach the tumor by craniofacial resection including removal of the left eye. First, using Weber-Fergusson incision, head and neck surgeons dissected the left face and cut the coronoid process of the mandible and zygomatic arch. Left fronto-temporal craniotomy was performed, and the anterior cranial base was exposed epidurally. The cavernous sinus was dissected epidurally and retracted posteriorly. An osteotomy was made in the anterior cranial base at the sphenoid body anterior to the foramen ovale. After cutting the hard palate and sphenoid floor, the tumor was resected en bloc (Figure 5B). Antero-middle skull base reconstruction was then performed by plastic surgeons using a rectus abdominis myocutaneous free flap and temporal fascia (Figure 5C). At 10 days after the operation, he presented with CSF leakage and resolved after bedrest in a semi-sitting position for 1 week. At 40 days after the operation, he left the hospital with no prognostic symptom. Follow-up examination and MRI after 2 years have shown no recurrent tumor (Figure 5D).
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Table 5. Cases with CS Involvement. Case Age Sex T Tumor Histology
Tumor
Management of CS
Outcome
Follow-up, d Recurrent Area
1 2 3
57 44 63
M 4b M 4b M 4b
SCC ACC SCC
Untreated Recurrent Recurrent
Type 3 Type 3 Type 2
Died Disease-free Died
7 4011 470
4 5
58 60
M 4b M 4b
SCC SCC
Untreated Recurrent
Type 2 Type 2
Died Died
1776 173
Complications
None None Local
Cerebral infarction Cerebral infarction Cerebral infarction, meningitis, pneumonia Distant Hydrocephalus Local and neck CSF leakage major
Abbreviations: ACC, adenoid cystic carcinoma; CS, cavernous sinus; CSF, cerebrospinal fluid leakage; SCC, squamous cell carcinoma.
Figure 5. (A) Preoperative T2-weighted magnetic resonance imaging (MRI). (B) Intraoperative picture after craniofacial resection. (C) Intraoperative picture after reconstruction. (D) Follow-up T2-weighted MRI.
Discussion When Ketcham et al14 first reported craniofacial resection for sinonasal carcinoma in 1963, craniofacial resection would occasionally lead to severe complications and was a challenging operation. Many recent studies have described good results for craniofacial resection of malignant skull base tumors.12,15-18 An international collaborative study showed a 5-year OS rate of 54% for malignant skull base tumors.19 Survival of patients with sinonasal malignancy has previously been studied, reporting a 5-year OS rate of 40% for all malignancies and 60% for sinonasal squamous cell carcinoma specifically.3,20 This study only included cases of locally advanced MSC classified as T4, finding a 5-year OS rate of 62.7% and, more particularly, a 5-year OS rate of 72.4% without cavernous sinus involvement. Considering the advanced stage, our outcomes were relatively favorable.
In the early period, we encountered severe CNS complications such as internal carotid artery occlusion, cerebral infarction, and meningitis, in all cases showing involvement of the cavernous sinus. Because all cases with involvement of the cavernous sinus experienced severe CNS complications, our data for CNS complications were worse than those of the international collaborative study. Although we performed excision of locally advanced MSC with involvement of the cavernous sinus in en bloc fashion using high-flow bypass in the early period of our experience, the severe perioperative complications encountered and poor postoperative prognosis led us to reconsider the surgical indications. After we stopped conducting craniofacial resection for cases with involvement of the cavernous sinus, the rate of severe CNS complications decreased, and the overall complication rate became acceptable. Medical comorbidity, prior radiation therapy, elderly patients (70 years old), and
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the extent of intracranial tumor involvement were independent predictors of postoperative complications.18,21,22 To perform accurate osteotomy around the cavernous sinus, we conducted surgical methods aimed at managing the cavernous sinus in en bloc resections of malignant skull base tumors as reported by Saito et al12 and performed craniofacial resection even if the T stage was T4b, such as with involvement of the cavernous sinus and orbital apex. By conducting the type 1 procedure for patients with involvement of the orbital apex, we can remove the tumor in an en bloc fashion completely and safely. Although technically possible, adding carotid resection to the surgical procedures increases the risk of postoperative cerebral infarction.12 Because of the severe complications in the early period and early recurrences after surgery, we are no longer performing surgical resection for patients with cavernous sinus involvement. Whether postoperative treatments such as radiotherapy and/or chemotherapy are needed after complete resection remains controversial. Outcomes after single-modality therapy are generally poor, so the postoperative period is generally considered the optimal timing for radiotherapy relative to surgery.3,23,24 Although little data are currently available regarding the efficiency of CCRT for locally advanced MSC,25 Kang et al26 reported that the combination of surgery, radiotherapy, and/or chemotherapy might be superior to CCRT for locally advanced MSC. Craniofacial resection could achieve good results for locally advanced MSC, but operative stress including excessive blood loss is never less and might lead to a fatal condition. Craniofacial resection is therefore not recommended to patients over 75 years old or with severe comorbidities. Focused on the functional and aesthetic problems, such as removal of an orbit, minimally invasive procedures have recently been reported. In well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal carcinoma results in acceptable oncologic outcomes.27,28 Superselective intra-arterial infusion of concomitant radiotherapy (RADPLAT) has been reported to result in favorable survival rates.29-31 Several papers have examined the efficiency of proton/heavy-ion therapy for managing locally advanced sinonasal malignancies.32-35 As radiotherapy, including CCRT, RADPLAT, and proton/heavy-ion therapy, becomes more popular, cases of recurrent MSC after radiotherapy therapy seem likely to increase in frequency. Few treatment options are available for patients with recurrent MSC after radiotherapy, so craniofacial resection in an en bloc fashion is set to play a more important role. This study was based on a relatively small and heterogeneous group of cases, from multiple perspectives: pathology, prior treatment, decisions about adjuvant treatment, treatment, and inclusion and exclusion criteria over the time period of the series. This represents a key weakness in our study, and the results need to be confirmed in a larger series of patients.
Conclusion The present study focused on locally advanced MSC with skull base involvement. With accurate osteotomy around the
cavernous sinus, we can remove the tumor in an en bloc fashion completely and safely. Even for cases of locally advanced MSC classified as T4, craniofacial resection in an en bloc fashion achieved a good survival rate. Author Contributions Naoki Nishio, data analysis, drafting, final approval, accountability for all aspects of the work; Yasushi Fujimoto, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Masazumi Fujii, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Kiyoshi Saito, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Mariko Hiramatsu, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Takashi Maruo, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Kenichiro Iwami, acquisition of data, design, revising critically for the area of neurosurgery, final approval; Yuzuru Kamei, acquisition of data, design, revising critically for the area of plastic reconstructive surgery, final approval; Shunjiro Yagi, acquisition of data, design, revising critically for the area of plastic reconstructive surgery, final approval; Masakatsu Takahashi, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Yuichiro Hayashi, acquisition of data, design, revising critically for the area of navigation system, final approval; Atsushi Ando, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval; Tsutomu Nakashima, acquisition of data, design, revising critically for the area of otorhinolaryngology, final approval.
Disclosures Competing interests: None. Sponsorships: None. Funding source: National Cancer Center Research and Development Fund (23-A-26), JSPS Grant-in-Aid for Research Activity Start-up. Request for proof reading.
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