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Cervical metastases from maxillary squamous cell carcinoma: retrospective analysis and review of the literature
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British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
Cervical metastases from maxillary squamous cell carcinoma: retrospective analysis and review of the literature Ayesha J. Dalal ∗ , Andrew S. McLennan Oral & Maxillofacial Surgery, Royal Devon & Exeter NHSFT, Barrack Road, Exeter EX2 5DW, United Kingdom Accepted 18 August 2013 Available online 14 September 2013
Abstract The purpose of this study was to define the incidence of cervical metastasis in squamous cell carcinoma (SCC) of the maxillary alveolus, hard palate and gingiva; to identify patterns of locoregional failure and to assess survival outcomes. We retrospectively analysed 30 patients treated for SCC of the maxillary alveolus and hard palate between 2000 and 2010. Parameters assessed included the incidence of cervical metastasis at presentation and recurrence, paying particular attention to tumour staging and survival outcomes. Of our 30 patients, 25 were confirmed to have T4 SCC of the maxillary alveolus and hard palate with bone invasion. Cervical metastases had been noted in 7 (23%) patients at initial presentation. A total of 9 (36%) patients developed regional failure in the pT4 SCC group shortly after primary resection. Patients with advanced primary SCC of the hard palate and maxillary alveolus (particularly when there was bone invasion) showed high rates of regional failure, and in most cases successful salvage was not achieved. Based on our findings and a review of the existing literature we strongly recommend elective neck dissection for patients with pT4 SCC of the maxillary alveolus and hard palate. © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: Cervical; Metastasis; Neck; Maxillary; Squamous cell carcinoma; Alveolus; Hard palate; Gingiva; Regional failure
Introduction There has been increasing interest in the management of squamous cell carcinoma (SCC) of the maxillary gingiva, alveolus and hard palate in the node negative neck. Several recently published studies have reported the incidence of cervical metastases from maxillary SCC, but to date we know of no randomised controlled trial that has validated these findings. SCC of the oral cavity has a high propensity to metastasise to cervical lymph nodes, and in their paper on the use of decision analysis in planning the management of the neck, Weiss et al.1 stated that: “if the probability of occult metastasis is greater than 20% then a neck dissection should be undertaken”. Other studies recommend elective neck dissection when the risk of occult metastasis exceeds 15–20%.2–5 ∗
Corresponding author. Tel.: +44 1392 403711; fax: +44 1392 402199. E-mail addresses: [email protected], [email protected] (A.J. Dalal), [email protected] (A.S. McLennan).
There is controversy about the treatment of the neck in patients with maxillary SCC and no sign of metastasis because of the lack of evidence of the incidence of metastasis. When there is no clinical or radiographically suspicious lymphadenopathy, management has traditionally been to watch and wait. However, we found that in an appreciable number of patients who presented with cervical metastases soon after primary resection, there had initially been no sign of metastatic disease in the neck. In this retrospective study we present our experience of the management of patients with maxillary SCC. We aim to establish the incidence of cervical metastasis and shed light on the management of the node negative neck.
Patients and methods This study includes consecutive patients with SCC of the maxillary alveolus, gingiva and hard palate, who were treated over 10 years between 2000 and 2010. Data fields included
0266-4356/$ – see front matter © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bjoms.2013.08.011
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
703
Table 1 Details of patients with maxillary squamous cell carcinoma. Case no.
Age (years)
Site
Nodal disease at presentation
TNM stage
Treatment
Recurrence
1
79
Palate
Yes
pT4N1
None
2 3
86 82
Alveolus Alveolus
No Yes
pT4 pT4N2c
4 5 6
79 81 75
Alveolus Alveolus Alveolus
No No No
pT4 pT4 pT4N0
7
65
Palate
Yes
pT4N1
8
55
Alveolus
No
pT4N0
9 10 11 12
73 70 68 69
Alveolus Alveolus Alveolus Alveolus
No No No No
pT4 pT4 pT4 pT4N0
13 14
78 75
Alveolus Palate
No No
pT4 pT4N0
15 16
69 65
Alveolus Palate
No No
pT4 pT4N0
17 18 19
60 55 52
Alveolus Alveolus Alveolus
No No Yes
pT4 pT4 pT4N2b
20
73
Alveolus
Yes
pT4N2c
21 22
80 69
No No
pT4N0 pT4N0
23
83
Alveolus Alveolus, hard palate Alveolus
Yes
pT4N1
24
62
Alveolus
Yes
pT4N2b
25 26 27 28 29 30
91 80 57 62 75 35
Alveolus Alveolus Palate Palate Palate Palate
No No No No No No
pT4 pT3 pT3 pT2 pT2 pT1
Resection, selective neck dissection Resection Resection, selective neck dissection, radiotherapy Resection, radiotherapy Resection, radiotherapy Resection, bilateral elective neck dissection, radiotherapy Resection, selective neck dissection, radiotherapy Resection, elective neck dissection Resection Resection, radiotherapy Resection, radiotherapy Resection, elective neck dissection Resection, radiotherapy Resection, elective neck dissection Resection Resection, elective neck dissection, radiotherapy Resection Resection, radiotherapy Resection, selective neck dissection, chemo radiotherapy Resection, bilateral selective neck dissection, radiotherapy Resection, radiotherapy Resection, elective neck dissection, radiotherapy Resection, selective neck dissection, radiotherapy Resection, selective neck dissection Resection Resection Resection Resection Resection Resection
age, histological type, site, staging of the primary tumour, nodal status, incidence of local, regional, or distant metastases and survival. Patients with SCC originating in the nasal cavity or maxillary sinus and other malignancies of the maxilla, were excluded. All patients had pre-operative magnetic resonance imaging (MRI) (base of skull to clavicle) or computed tomography (CT) (base of skull to diaphragm), or both, to detect the presence of bony invasion and cervical lymphadenopathy. Lymphadenopathy is defined as a lymph node with a short axis of more than 10 mm or with a central area of necrosis. Suspicious nodes were investigated using ultrasound-guided fine needle aspiration (FNA). Tumours were staged using the International
Neck Neck Alveolus and neck None None Palate None Neck None Neck None None None Neck None Neck and distant Neck and distant None
Neck None None Alveolus None None None Neck None Palate None
Union against Cancer Classification (UICC) for TNM (Table 1). Elective neck dissection was not part of our routine management but depended on the surgeon’s preference. If done, it included levels I–IV of the ipsilateral neck. The decision to offer radiotherapy was made after multidisciplinary discussion.
Results The study group comprised 30 patients. There were 21 men and 9 women, mean age 70 years (range 35–91). All patients were followed up for 60 months or until death in accordance
704
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
with guidelines approved by the National Institute for Health and Care Excellence.
Table 2 Incidence of regional recurrence in patients with pT4 SCC with respect to treatment modalities.
Management
pT4 maxillary SCC
No. of patients (n = 25)
Regional recurrence
Resection and neck dissection Resection, neck dissection and radiotherapy Resection and radiotherapy Resection only
5 8 7 5
0 2 3 4
All patients underwent resection of maxillary SCC, which included partial maxillectomy or hemimaxillectomy. Reconstruction was by means of obturation, temporalis muscle flap, or vascularised free flap. Patients with clinically invaded necks had levels I–IV neck dissection at the time of primary resection. Adjuvant radiotherapy was offered if histopathological examination confirmed multiple or extracapsular nodal disease, and was also advocated for close margins. TNM staging Of the 30 patients, maxillary SCC was confirmed as pT4 in 25, pT3 in 2, pT2 in 2, and pT1 in 1. On initial presentation 7 patients (23%) had clinically suspicious cervical lymphadenopathy. MRI or CT from the base of the skull to the clavicle showed multiple nodes larger than 10 mm, which were distributed among level I (6 nodes), level II (5 nodes), and level III (4 nodes). Ultrasound-guided fine needle aspiration cytology (FNAC) confirmed that all had metastatic SCC and selective neck dissection at the time of primary resection confirmed this. Two patients had aggressive disease (pT4N2c) with invaded ipsilateral and contralateral nodes and extracapsular spread with perineural invasion. They subsequently died of disease 2 and 8 months after operation. Patients with no sign of metastasis in the neck The 5 patients with pT1 to pT3 disease and no sign of metastases in the neck on presentation, had resection only. Of the 18 who had pT4 SCC and no sign of metastases at presentation, only 6 had elective neck dissection either at the discretion of the surgeon or to gain access to the vessels for microvascular reconstruction. They were closely followed up with clinical examination and further imaging where indicated.
Table 3 Survival status in relation to staging of neck at initial presentation. Outcome
cN0 (n = 23)
cN+ (n = 7)
Cured and discharged at 5 years Free of disease and under watchful wait Died of disease within 5-year period Died of other cause within 5-year period
11 5 5 2
1 3 2 1
were in levels I and II of the neck. Cervical metastases developed after an average of 7 months following primary resection and majority of these patients died within 18 months of recurrence. Two patients (6%) also developed distant metastases to the lung, brain, and abdomen, and died of disease soon after. Patterns of recurrence for pT4 SCC are shown in Table 2. Outcomes All patients were followed up for 5 years or until death. No cervical disease has been noted to date in the 3 patients with pT1 and pT2 disease (100% survival at 5-year follow-up). 8 of 25 patients in the pT4 group were free of disease at 5 years; survival rate 32%. However, a further 8 (32%) patients in the pT4 group remain free of disease and under close vigilance. We lost 9 (36%) patients of the pT4 group to disease or other cause. Overall outcome and survival rates are shown in Table 3.
Discussion Radiotherapy Radiotherapy alone was not offered, and surgery was the first line of treatment in all patients. Between 2000 and 2005 adjuvant radiotherapy was not considered for completely excised maxillary SCC, but from 2005 to 2010 the multidisciplinary consensus was to offer adjuvant radiotherapy to all patients with pT4 SCC. Therefore, 15 of the 25 patients with pT4 SCC were given 60 Gy of adjuvant radiotherapy aimed to include the site of the primary tumour and ipsilateral neck. Recurrence The 4 patients (13%) who had local failure underwent further resection. Regional failure was noted in 10 (33%): majority of which were in the pT4 group. Majority of the metastatic nodes
There is no consensus on the management of the neck in patients with maxillary SCC because of the scarcity of published papers on the subject. Previously it was thought that the risk of occult metastases from maxillary SCC was low in comparison with SCC of the tongue, floor of the mouth, and mandible, which have been studied extensively, and have been reported as having an incidence for occult disease of more than 20%. Elective neck dissection is widely accepted when the risk of occult metastases exceeds 15–20%.1–4 In our series the incidence of cervical metastases at presentation from SCC of the maxillary alveolus, gingiva and hard palate was 23% (7 of 30 patients). This is consistent with current studies that report incidence between 12% and 29%.5–12 The findings are also similar to the rate of occult metastases from SCC of the tongue and floor of the mouth.5
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
As we only had a few patients with pT1 to pT3 disease we felt there was no merit in including them in the discussion and from this point we discuss only those with pT4 disease. There was a 36% incidence of regional failure (9 of 25 patients) in this group. Interestingly, 4 out of the 5 patients who had resection of tumour alone went on to develop cervical metastases, which suggests a high propensity for occult disease. Of the 7 who had resection and radiotherapy (to tumour site and ipsilateral neck), 3 developed regional failure. 2 of 8 patients who had resection, elective neck dissection, and adjuvant radiotherapy presented with recurrent cervical metastases. Because of the limited sample size it was difficult to show significance regarding the role of radiotherapy and rate of cervical metastasis, but based on our findings we could hypothesise that radiotherapy to the neck with or without elective neck dissection reduces the rate of regional failure when compared with resection alone. All 5 patients who had primary resection and elective neck dissection are free of cervical disease to date. The reasons behind the different treatments were multifactorial, but mainly depended on the patient’s coexisting conditions and the surgeon’s preference. Our findings highlight the importance of careful consideration of elective neck dissection when treating pT4 maxillary SCC. Our 5 year survival rate was 54.5% which is consistent with previously reported rates of 48% to 58%.5–13 Salvage operations in the 9 patients who developed regional failure were unsuccessful, and 7 died from disease within 18 months of cervical recurrence. One patient with pT4N2c disease developed a large necrotic node in level II of the ipsilateral neck 5 months after primary operation, and MRI confirmed extensive cervical disease. Palliative radiotherapy was administered to bilateral neck but the patient died of recurrent disease one month later. Another patient developed metastatic spread to the paratracheal nodes 2 months after primary operation and died of disease soon after. One patient is currently undergoing palliative chemoradiotherapy for infratemporal metastatic spread 12 months after primary operation. These results highlight the importance of aggressive management of maxillary SCC. Recent retrospective studies have shown that maxillary SCC has a similar propensity to metastasise as SCC of the tongue and floor of the mouth. Poeschl et al.6 recently published a retrospective study of 74 patients over 15 years who were treated in Vienna for maxillary SCC. Patients with pT4 SCC and no sign of metastases in the neck were divided into 2 groups: one group had elective neck dissection (n = 27) and the other did not (n = 16). There was a 17% incidence of regional failure in those who had neck dissection and an 18% incidence in those who did not. The authors recommended elective neck dissection for advanced T4 SCC as they found that it improved overall survival. Morris et al.7 published a 21-year study of 139 cases of maxillary SCC, which is the largest published sample size. They reported regional failure in 28.4% of patients and the pT4 group showed a 37.3% incidence of cervical metastases.
705
They analysed their data using multivariate Cox regression analysis and reported that salvage was unsuccessful in 65.6% of the patients with regional recurrence. They concluded that elective neck dissection is prudent in patients with locally advanced maxillary SCC. Their findings were comparable to our study despite the difference in sample size. Mourouzis et al.8 reported a 23.5% incidence of cervical metastases at presentation with maxillary SCC. Two of 13 patients who initially had no sign of metastases in the neck developed cervical disease, which indicates the presence of occult metastases. Five-year survival was 58%. In a multicentre study over a 10-year period, Beltramini et al.9 reported on 65 patients with SCC of the maxillary alveolar ridge and hard palate. The incidence of cervical metastases on presentation was 12.3% and overall incidence was 21.5%. The groups were divided according to stage and the authors concluded that elective neck dissection should be done in those with T3 and T4 maxillary SCC, but they commented that their results could not be considered significant because of the small sample size. Yorozu et al.10 retrospectively assessed 19 patients treated only with external beam radiotherapy for SCC of the hard palate and reported 5-year survival of 48%. They commented that it was safe and tolerated well by patients. The incidence of cervical metastases in this group was 26%. Following a review of published papers and based on our own experience, we do not recommend radiotherapy as a first-line treatment for the neck when there is no sign of metastases, as the incidence of regional failure with radiotherapy alone is 42.8%. It is well known that salvage operations after radiotherapy are notoriously difficult and often unsuccessful. Ogura et al.11 looked at maxillary bony invasion by gingival SCC in 21 patients and reported a 28.5% incidence of cervical disease at presentation. They concluded that cervical spread was closely related to the presence of maxillary bony invasion. Simental et al12 studied 26 patients and reported a 27% rate of occult metastases and an overall incidence of 34.6%. In a retrospective study over 9 years, Kruse and Grätz13 analysed 30 patients with maxillary SCC. The initial rate of cervical metastasis was 13% and overall incidence was 36.7%. Montes and Schmidt14 reported on 14 patients with maxillary SCC, 20% of which had some metastases at presentation. After resection 21.4% developed cervical metastases soon after operation (average of 9.75 months). Brown et al.15 recently published their first report on elective neck dissection in the management of SCC of the maxillary sinus. They retrospectively reviewed 18 patients and reported a 12% incidence of regional recurrence and a 21% incidence overall of cervical metastases. They concluded that they had found no evidence to suggest that the operation was beneficial. In our study, primary SCC of the maxillary sinus was excluded as this is often treated by another specialty.
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A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
Conclusion This study has limitations because of its retrospective nature and small sample size. However, as maxillary SCC is rare it would be difficult to carry out a prospective study because of the time it would take to obtain a sample size large enough to obtain statistical significance. A multicentre randomised controlled trial would be required to show whether elective neck dissection improves recurrence and survival outcomes, but it would be hard to gain ethical approval for this in the UK because recent literature confirms the high incidence of regional failure. We would like to add to the literature a 36% incidence of cervical metastases in our pT4 patient group. Based on our findings we strongly recommend elective neck dissection for patients with pT4 SCC of the maxillary alveolus and hard palate.
References 1. Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg 1994;120:699–702. 2. Shah JP. Head and neck surgery and oncology. 3rd ed. Mosby: Edinburgh; 2003. p. 353–8. 3. Haddakin KJ, Soutar DS, Oliver RJ, Webster MH, Robertson AG, MacDonald DG. Improved survival for patients with clinically T1/T2, N0 tongue tumours undergoing a prophylactic neck dissection. Head Neck 1999;21:517–25. 4. Pitman KT. Rationale for elective neck dissection. Am J Otolaryngol 2000;21:31–7.
5. Shah JP, Candela FC, Poddar AK. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 1990;66:109–13. 6. Poeschl PW, Seemann R, Czembirek C, et al. Impact of elective neck dissection on regional recurrence and survival in cN0 staged oral maxillary squamous cell carcinoma. Oral Oncol 2012;48:173–8. 7. Morris LG, Patel SG, Shah JP, et al. High rates of regional failure in squamous cell carcinoma of the hard palate and maxillary alveolus. Head Neck 2011;33:824–30. 8. Mourouzis C, Pratt C, Brennan PA. Squamous cell carcinoma of the maxillary gingiva, alveolus, and hard palate: is there a need for elective neck dissection? Br J Oral Maxillofac Surg 2010;48: 345–8. 9. Beltramini GA, Massarelli O, Demarchi M, et al. Is neck dissection needed in squamous-cell carcinoma of the maxillary gingiva, alveolus, and hard palate? A multicentre Italian study of 65 cases and literature review. Oral Oncol 2012;48:97–101. 10. Yorozu A, Sykes AJ, Slevin NJ. Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases. Oral Oncol 2001;37:493–7. 11. Ogura I, Kurabayashi T, Sasaki T, et al. Maxillary bone invasion by gingival carcinoma as an indicator of cervical metastasis. Dentomaxillofac Radiol 2003;32:291–4. 12. Simental Jr AA, Johnson JT, Myers EN. Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and hard palate. Laryngoscope 2006;116:1682–4. 13. Kruse AL, Grätz KW. Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 9 years. Head Neck Oncol 2009;1:28–32. 14. Montes DM, Schmidt BL. Oral maxillary squamous cell carcinoma: management of the clinically negative neck. J Oral Maxillofac Surg 2008;66:762–6. 15. Brown JS, Bekiroglu F, Shaw RJ, et al. First report of elective selective neck dissection in the management of squamous cell carcinoma of the maxillary sinus. Br J Oral Maxillofac Surg 2013;51:103–7.
British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
Cervical metastases from maxillary squamous cell carcinoma: retrospective analysis and review of the literature Ayesha J. Dalal ∗ , Andrew S. McLennan Oral & Maxillofacial Surgery, Royal Devon & Exeter NHSFT, Barrack Road, Exeter EX2 5DW, United Kingdom Accepted 18 August 2013 Available online 14 September 2013
Abstract The purpose of this study was to define the incidence of cervical metastasis in squamous cell carcinoma (SCC) of the maxillary alveolus, hard palate and gingiva; to identify patterns of locoregional failure and to assess survival outcomes. We retrospectively analysed 30 patients treated for SCC of the maxillary alveolus and hard palate between 2000 and 2010. Parameters assessed included the incidence of cervical metastasis at presentation and recurrence, paying particular attention to tumour staging and survival outcomes. Of our 30 patients, 25 were confirmed to have T4 SCC of the maxillary alveolus and hard palate with bone invasion. Cervical metastases had been noted in 7 (23%) patients at initial presentation. A total of 9 (36%) patients developed regional failure in the pT4 SCC group shortly after primary resection. Patients with advanced primary SCC of the hard palate and maxillary alveolus (particularly when there was bone invasion) showed high rates of regional failure, and in most cases successful salvage was not achieved. Based on our findings and a review of the existing literature we strongly recommend elective neck dissection for patients with pT4 SCC of the maxillary alveolus and hard palate. © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: Cervical; Metastasis; Neck; Maxillary; Squamous cell carcinoma; Alveolus; Hard palate; Gingiva; Regional failure
Introduction There has been increasing interest in the management of squamous cell carcinoma (SCC) of the maxillary gingiva, alveolus and hard palate in the node negative neck. Several recently published studies have reported the incidence of cervical metastases from maxillary SCC, but to date we know of no randomised controlled trial that has validated these findings. SCC of the oral cavity has a high propensity to metastasise to cervical lymph nodes, and in their paper on the use of decision analysis in planning the management of the neck, Weiss et al.1 stated that: “if the probability of occult metastasis is greater than 20% then a neck dissection should be undertaken”. Other studies recommend elective neck dissection when the risk of occult metastasis exceeds 15–20%.2–5 ∗
Corresponding author. Tel.: +44 1392 403711; fax: +44 1392 402199. E-mail addresses: [email protected], [email protected] (A.J. Dalal), [email protected] (A.S. McLennan).
There is controversy about the treatment of the neck in patients with maxillary SCC and no sign of metastasis because of the lack of evidence of the incidence of metastasis. When there is no clinical or radiographically suspicious lymphadenopathy, management has traditionally been to watch and wait. However, we found that in an appreciable number of patients who presented with cervical metastases soon after primary resection, there had initially been no sign of metastatic disease in the neck. In this retrospective study we present our experience of the management of patients with maxillary SCC. We aim to establish the incidence of cervical metastasis and shed light on the management of the node negative neck.
Patients and methods This study includes consecutive patients with SCC of the maxillary alveolus, gingiva and hard palate, who were treated over 10 years between 2000 and 2010. Data fields included
0266-4356/$ – see front matter © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bjoms.2013.08.011
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
703
Table 1 Details of patients with maxillary squamous cell carcinoma. Case no.
Age (years)
Site
Nodal disease at presentation
TNM stage
Treatment
Recurrence
1
79
Palate
Yes
pT4N1
None
2 3
86 82
Alveolus Alveolus
No Yes
pT4 pT4N2c
4 5 6
79 81 75
Alveolus Alveolus Alveolus
No No No
pT4 pT4 pT4N0
7
65
Palate
Yes
pT4N1
8
55
Alveolus
No
pT4N0
9 10 11 12
73 70 68 69
Alveolus Alveolus Alveolus Alveolus
No No No No
pT4 pT4 pT4 pT4N0
13 14
78 75
Alveolus Palate
No No
pT4 pT4N0
15 16
69 65
Alveolus Palate
No No
pT4 pT4N0
17 18 19
60 55 52
Alveolus Alveolus Alveolus
No No Yes
pT4 pT4 pT4N2b
20
73
Alveolus
Yes
pT4N2c
21 22
80 69
No No
pT4N0 pT4N0
23
83
Alveolus Alveolus, hard palate Alveolus
Yes
pT4N1
24
62
Alveolus
Yes
pT4N2b
25 26 27 28 29 30
91 80 57 62 75 35
Alveolus Alveolus Palate Palate Palate Palate
No No No No No No
pT4 pT3 pT3 pT2 pT2 pT1
Resection, selective neck dissection Resection Resection, selective neck dissection, radiotherapy Resection, radiotherapy Resection, radiotherapy Resection, bilateral elective neck dissection, radiotherapy Resection, selective neck dissection, radiotherapy Resection, elective neck dissection Resection Resection, radiotherapy Resection, radiotherapy Resection, elective neck dissection Resection, radiotherapy Resection, elective neck dissection Resection Resection, elective neck dissection, radiotherapy Resection Resection, radiotherapy Resection, selective neck dissection, chemo radiotherapy Resection, bilateral selective neck dissection, radiotherapy Resection, radiotherapy Resection, elective neck dissection, radiotherapy Resection, selective neck dissection, radiotherapy Resection, selective neck dissection Resection Resection Resection Resection Resection Resection
age, histological type, site, staging of the primary tumour, nodal status, incidence of local, regional, or distant metastases and survival. Patients with SCC originating in the nasal cavity or maxillary sinus and other malignancies of the maxilla, were excluded. All patients had pre-operative magnetic resonance imaging (MRI) (base of skull to clavicle) or computed tomography (CT) (base of skull to diaphragm), or both, to detect the presence of bony invasion and cervical lymphadenopathy. Lymphadenopathy is defined as a lymph node with a short axis of more than 10 mm or with a central area of necrosis. Suspicious nodes were investigated using ultrasound-guided fine needle aspiration (FNA). Tumours were staged using the International
Neck Neck Alveolus and neck None None Palate None Neck None Neck None None None Neck None Neck and distant Neck and distant None
Neck None None Alveolus None None None Neck None Palate None
Union against Cancer Classification (UICC) for TNM (Table 1). Elective neck dissection was not part of our routine management but depended on the surgeon’s preference. If done, it included levels I–IV of the ipsilateral neck. The decision to offer radiotherapy was made after multidisciplinary discussion.
Results The study group comprised 30 patients. There were 21 men and 9 women, mean age 70 years (range 35–91). All patients were followed up for 60 months or until death in accordance
704
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
with guidelines approved by the National Institute for Health and Care Excellence.
Table 2 Incidence of regional recurrence in patients with pT4 SCC with respect to treatment modalities.
Management
pT4 maxillary SCC
No. of patients (n = 25)
Regional recurrence
Resection and neck dissection Resection, neck dissection and radiotherapy Resection and radiotherapy Resection only
5 8 7 5
0 2 3 4
All patients underwent resection of maxillary SCC, which included partial maxillectomy or hemimaxillectomy. Reconstruction was by means of obturation, temporalis muscle flap, or vascularised free flap. Patients with clinically invaded necks had levels I–IV neck dissection at the time of primary resection. Adjuvant radiotherapy was offered if histopathological examination confirmed multiple or extracapsular nodal disease, and was also advocated for close margins. TNM staging Of the 30 patients, maxillary SCC was confirmed as pT4 in 25, pT3 in 2, pT2 in 2, and pT1 in 1. On initial presentation 7 patients (23%) had clinically suspicious cervical lymphadenopathy. MRI or CT from the base of the skull to the clavicle showed multiple nodes larger than 10 mm, which were distributed among level I (6 nodes), level II (5 nodes), and level III (4 nodes). Ultrasound-guided fine needle aspiration cytology (FNAC) confirmed that all had metastatic SCC and selective neck dissection at the time of primary resection confirmed this. Two patients had aggressive disease (pT4N2c) with invaded ipsilateral and contralateral nodes and extracapsular spread with perineural invasion. They subsequently died of disease 2 and 8 months after operation. Patients with no sign of metastasis in the neck The 5 patients with pT1 to pT3 disease and no sign of metastases in the neck on presentation, had resection only. Of the 18 who had pT4 SCC and no sign of metastases at presentation, only 6 had elective neck dissection either at the discretion of the surgeon or to gain access to the vessels for microvascular reconstruction. They were closely followed up with clinical examination and further imaging where indicated.
Table 3 Survival status in relation to staging of neck at initial presentation. Outcome
cN0 (n = 23)
cN+ (n = 7)
Cured and discharged at 5 years Free of disease and under watchful wait Died of disease within 5-year period Died of other cause within 5-year period
11 5 5 2
1 3 2 1
were in levels I and II of the neck. Cervical metastases developed after an average of 7 months following primary resection and majority of these patients died within 18 months of recurrence. Two patients (6%) also developed distant metastases to the lung, brain, and abdomen, and died of disease soon after. Patterns of recurrence for pT4 SCC are shown in Table 2. Outcomes All patients were followed up for 5 years or until death. No cervical disease has been noted to date in the 3 patients with pT1 and pT2 disease (100% survival at 5-year follow-up). 8 of 25 patients in the pT4 group were free of disease at 5 years; survival rate 32%. However, a further 8 (32%) patients in the pT4 group remain free of disease and under close vigilance. We lost 9 (36%) patients of the pT4 group to disease or other cause. Overall outcome and survival rates are shown in Table 3.
Discussion Radiotherapy Radiotherapy alone was not offered, and surgery was the first line of treatment in all patients. Between 2000 and 2005 adjuvant radiotherapy was not considered for completely excised maxillary SCC, but from 2005 to 2010 the multidisciplinary consensus was to offer adjuvant radiotherapy to all patients with pT4 SCC. Therefore, 15 of the 25 patients with pT4 SCC were given 60 Gy of adjuvant radiotherapy aimed to include the site of the primary tumour and ipsilateral neck. Recurrence The 4 patients (13%) who had local failure underwent further resection. Regional failure was noted in 10 (33%): majority of which were in the pT4 group. Majority of the metastatic nodes
There is no consensus on the management of the neck in patients with maxillary SCC because of the scarcity of published papers on the subject. Previously it was thought that the risk of occult metastases from maxillary SCC was low in comparison with SCC of the tongue, floor of the mouth, and mandible, which have been studied extensively, and have been reported as having an incidence for occult disease of more than 20%. Elective neck dissection is widely accepted when the risk of occult metastases exceeds 15–20%.1–4 In our series the incidence of cervical metastases at presentation from SCC of the maxillary alveolus, gingiva and hard palate was 23% (7 of 30 patients). This is consistent with current studies that report incidence between 12% and 29%.5–12 The findings are also similar to the rate of occult metastases from SCC of the tongue and floor of the mouth.5
A.J. Dalal, A.S. McLennan / British Journal of Oral and Maxillofacial Surgery 51 (2013) 702–706
As we only had a few patients with pT1 to pT3 disease we felt there was no merit in including them in the discussion and from this point we discuss only those with pT4 disease. There was a 36% incidence of regional failure (9 of 25 patients) in this group. Interestingly, 4 out of the 5 patients who had resection of tumour alone went on to develop cervical metastases, which suggests a high propensity for occult disease. Of the 7 who had resection and radiotherapy (to tumour site and ipsilateral neck), 3 developed regional failure. 2 of 8 patients who had resection, elective neck dissection, and adjuvant radiotherapy presented with recurrent cervical metastases. Because of the limited sample size it was difficult to show significance regarding the role of radiotherapy and rate of cervical metastasis, but based on our findings we could hypothesise that radiotherapy to the neck with or without elective neck dissection reduces the rate of regional failure when compared with resection alone. All 5 patients who had primary resection and elective neck dissection are free of cervical disease to date. The reasons behind the different treatments were multifactorial, but mainly depended on the patient’s coexisting conditions and the surgeon’s preference. Our findings highlight the importance of careful consideration of elective neck dissection when treating pT4 maxillary SCC. Our 5 year survival rate was 54.5% which is consistent with previously reported rates of 48% to 58%.5–13 Salvage operations in the 9 patients who developed regional failure were unsuccessful, and 7 died from disease within 18 months of cervical recurrence. One patient with pT4N2c disease developed a large necrotic node in level II of the ipsilateral neck 5 months after primary operation, and MRI confirmed extensive cervical disease. Palliative radiotherapy was administered to bilateral neck but the patient died of recurrent disease one month later. Another patient developed metastatic spread to the paratracheal nodes 2 months after primary operation and died of disease soon after. One patient is currently undergoing palliative chemoradiotherapy for infratemporal metastatic spread 12 months after primary operation. These results highlight the importance of aggressive management of maxillary SCC. Recent retrospective studies have shown that maxillary SCC has a similar propensity to metastasise as SCC of the tongue and floor of the mouth. Poeschl et al.6 recently published a retrospective study of 74 patients over 15 years who were treated in Vienna for maxillary SCC. Patients with pT4 SCC and no sign of metastases in the neck were divided into 2 groups: one group had elective neck dissection (n = 27) and the other did not (n = 16). There was a 17% incidence of regional failure in those who had neck dissection and an 18% incidence in those who did not. The authors recommended elective neck dissection for advanced T4 SCC as they found that it improved overall survival. Morris et al.7 published a 21-year study of 139 cases of maxillary SCC, which is the largest published sample size. They reported regional failure in 28.4% of patients and the pT4 group showed a 37.3% incidence of cervical metastases.
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They analysed their data using multivariate Cox regression analysis and reported that salvage was unsuccessful in 65.6% of the patients with regional recurrence. They concluded that elective neck dissection is prudent in patients with locally advanced maxillary SCC. Their findings were comparable to our study despite the difference in sample size. Mourouzis et al.8 reported a 23.5% incidence of cervical metastases at presentation with maxillary SCC. Two of 13 patients who initially had no sign of metastases in the neck developed cervical disease, which indicates the presence of occult metastases. Five-year survival was 58%. In a multicentre study over a 10-year period, Beltramini et al.9 reported on 65 patients with SCC of the maxillary alveolar ridge and hard palate. The incidence of cervical metastases on presentation was 12.3% and overall incidence was 21.5%. The groups were divided according to stage and the authors concluded that elective neck dissection should be done in those with T3 and T4 maxillary SCC, but they commented that their results could not be considered significant because of the small sample size. Yorozu et al.10 retrospectively assessed 19 patients treated only with external beam radiotherapy for SCC of the hard palate and reported 5-year survival of 48%. They commented that it was safe and tolerated well by patients. The incidence of cervical metastases in this group was 26%. Following a review of published papers and based on our own experience, we do not recommend radiotherapy as a first-line treatment for the neck when there is no sign of metastases, as the incidence of regional failure with radiotherapy alone is 42.8%. It is well known that salvage operations after radiotherapy are notoriously difficult and often unsuccessful. Ogura et al.11 looked at maxillary bony invasion by gingival SCC in 21 patients and reported a 28.5% incidence of cervical disease at presentation. They concluded that cervical spread was closely related to the presence of maxillary bony invasion. Simental et al12 studied 26 patients and reported a 27% rate of occult metastases and an overall incidence of 34.6%. In a retrospective study over 9 years, Kruse and Grätz13 analysed 30 patients with maxillary SCC. The initial rate of cervical metastasis was 13% and overall incidence was 36.7%. Montes and Schmidt14 reported on 14 patients with maxillary SCC, 20% of which had some metastases at presentation. After resection 21.4% developed cervical metastases soon after operation (average of 9.75 months). Brown et al.15 recently published their first report on elective neck dissection in the management of SCC of the maxillary sinus. They retrospectively reviewed 18 patients and reported a 12% incidence of regional recurrence and a 21% incidence overall of cervical metastases. They concluded that they had found no evidence to suggest that the operation was beneficial. In our study, primary SCC of the maxillary sinus was excluded as this is often treated by another specialty.
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Conclusion This study has limitations because of its retrospective nature and small sample size. However, as maxillary SCC is rare it would be difficult to carry out a prospective study because of the time it would take to obtain a sample size large enough to obtain statistical significance. A multicentre randomised controlled trial would be required to show whether elective neck dissection improves recurrence and survival outcomes, but it would be hard to gain ethical approval for this in the UK because recent literature confirms the high incidence of regional failure. We would like to add to the literature a 36% incidence of cervical metastases in our pT4 patient group. Based on our findings we strongly recommend elective neck dissection for patients with pT4 SCC of the maxillary alveolus and hard palate.
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5. Shah JP, Candela FC, Poddar AK. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer 1990;66:109–13. 6. Poeschl PW, Seemann R, Czembirek C, et al. Impact of elective neck dissection on regional recurrence and survival in cN0 staged oral maxillary squamous cell carcinoma. Oral Oncol 2012;48:173–8. 7. Morris LG, Patel SG, Shah JP, et al. High rates of regional failure in squamous cell carcinoma of the hard palate and maxillary alveolus. Head Neck 2011;33:824–30. 8. Mourouzis C, Pratt C, Brennan PA. Squamous cell carcinoma of the maxillary gingiva, alveolus, and hard palate: is there a need for elective neck dissection? Br J Oral Maxillofac Surg 2010;48: 345–8. 9. Beltramini GA, Massarelli O, Demarchi M, et al. Is neck dissection needed in squamous-cell carcinoma of the maxillary gingiva, alveolus, and hard palate? A multicentre Italian study of 65 cases and literature review. Oral Oncol 2012;48:97–101. 10. Yorozu A, Sykes AJ, Slevin NJ. Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases. Oral Oncol 2001;37:493–7. 11. Ogura I, Kurabayashi T, Sasaki T, et al. Maxillary bone invasion by gingival carcinoma as an indicator of cervical metastasis. Dentomaxillofac Radiol 2003;32:291–4. 12. Simental Jr AA, Johnson JT, Myers EN. Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and hard palate. Laryngoscope 2006;116:1682–4. 13. Kruse AL, Grätz KW. Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 9 years. Head Neck Oncol 2009;1:28–32. 14. Montes DM, Schmidt BL. Oral maxillary squamous cell carcinoma: management of the clinically negative neck. J Oral Maxillofac Surg 2008;66:762–6. 15. Brown JS, Bekiroglu F, Shaw RJ, et al. First report of elective selective neck dissection in the management of squamous cell carcinoma of the maxillary sinus. Br J Oral Maxillofac Surg 2013;51:103–7.