Combined treatment of adenoid cystic carcinoma of the salivary glands

Copyright© Munksgaard2000

Int. J. OralMaxlllofae. Surg. 2000,"29:277-279 Printed in Denmark. All rights reserved

IntemationaIJoumdof

Oral& MaxillofacialSurgery ISSN 0901-5027

Combined treatment of adenoid cystic carcinoma of the salivary glands

C. M. E. Avery 1, A. B. Moody 1, F. E. McKinna 2, J. Taylor ~, J. M. Henk 2, J, D, Langdon ~ 1Department of Oral and Maxillofacial Surgery, King's College Hospital, London; 2Department of Clinical Oncology, The Royal Marsden Hospital, London, UK

C. M. E. Avery, A. B. Moody, F. E. McKinna, J. Taylor, J. M. Henk, J. D. Langdon: Combined treatment o f adenoid cystic carcinoma o f the salivary glands. Int. J. Oral Maxillofac. Surg. 2000; 29: 277-279. © Munksgaard, 2000 Abstract. A retrospective review of the experience of a single surgeon over a 20year period is presented. Fifteen patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands underwent combined treatment with wide local excision and radical postoperative radiotherapy. The actuarial survival is 100% at 5 years and 62% at 10 and 15 years. The disease-specific survival is 100% at 5 years and 86% at 10 and 15 years. There were no loco-regional recurrences. Wide local excision and radical postoperative radiotherapy seems to be an effective treatment for adenoid cystic carcinoma of the salivary glands.

A d e n o i d cystic carcinoma of the salivary glands is a slow-growing malignant t u m o u r characterised by wide local infiltration, perineural spread and a propensity for local recurrence. Locoregional lymphatic disease is uncomm o n but late distant metastases are relatively frequent 6. Typical survival figures are 73%, 45% and 35% at 5, 10 and 15 years, respectively 14. Several authors have reported improved control of local disease with a combination of surgery and radiotherapyl,S 8,10 i2,14. However, the indications for radiotherapy and the regimens used have varied considerably. There have been no reports o f a single surgeon using a combination of surgery and radical postoperative radiotherapy for all patients. We report the experience of the senior surgical author (JDL) over a 20-year period.

were treated (Table 1). The mean age at presentation was 53 years and 1 month (51 years 6 months for women, 54 years 7 months for men, range 34 70 years). The male (5) to female (10) ratio was 1 to 2. The mean followup was nine years (range: 3 years 5 months to 18 years 11 months). Five additional patients were excluded, 2 because they did not receive radiotherapy (one was too frail and the second declined treatment) and 3 because they had less than 1 year follow-up. The database is regularly updated by the senior surgical author (JDL), and a chest radiograph and liver function tests are performed annually. Tumours were clinically and pathologically staged according to the International Union Against Cancer TNM classification, 5th edition 13. Sixty-six percent (4) of the major salivary gland disease was stage 2 and fifty-five percent (5) of palatal and buccal lesions were stage 4 (Table 1). All specimens were independently examined by at least two pathologists and the majority were reviewed by the United Kingdom salivary gland tumour panel. A diagnosis of low-grade polymorphous adenocarcinoma was specifically excluded.

Material and methods

Combined treatment

Between 1978 and 1998, 15 consecutive patients with primary adenoid cystic carcinoma of the major (6) or minor (9) salivary glands

Fifteen patients underwent combined treatment with surgery and postoperative radiotherapy.

Key words: adenoid cystic carcinoma; salivary glands; surgery; radiotherapy. Accepted for publication 29 September 1999

Surgical treatment The aim was wide local excision with a margin of 1 to 2 cm depending on the site of the primary tumour. Lesions of the palate were excised by palatal fenestration or partial maxillectomy, submandibular and sublingual glands by extra-capsular dissection and the single parotid tumour by superficial parotidectomy. None of the patients presented with cervical lymphadenopathy and elective neck dissection was not performed.

Radiotherapy Twelve patients received radical postoperative radiotherapy with a daily fractionation of 2 Gy up to a maximum dose of 65 Gy (range 54-65 Gy); 3 patients received a slightly lower dose in 15 fractions (range 50-53 Gy). The mean dose was 59 Gy (Table 1). The radiotherapy field included the primary tumour site and the skull base or neck as required. There were no significant complications. One patient had radiotherapy abroad and the details were not available (patient 11), while another had additional chemotherapy (patient 5). Kaplan-Meier actuarial survival and disease-specific survival curves were generated.

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Table 1. Patient details Site 1. Parotid 2. Submandibular 3. Submandibular 4. Sublingual 5. Sublingual 6. Sublingual 7. Palate 8. Palate 9. Buccal 10. Palate 11. Palate 12. Buccal 13. Buccal 14. Palate 15. Palate

Pathological stage

Procedure

Radiotherapy (Gy/fraction/days)

Margin

Local recurrence

2 1 2 2 2 1 4 1 4 1 4 1 4 4 1

Parotidectomy Excision Excision Excision Excision Excision Partial maxillectomy Fenestration Partial maxillectomy Fenestration Partial maxillectomy Excision Excision Partial maxillectomy Excision

60130/42 60130/44 53/16139 64/321124 61/31156" 50/15/42 60/30/42 60/30/51 60]27/46 52/15/43 ** 65132/49 54/27/37 60/30/42 60/30/42

Not clear Clear Clear Not clear Clear Clear Clear Not clear Not clear Clear Not clear Not clear Not clear Not clear Not clear

-

Distant metastases

Follow-up

2 yr 3 m 2 yr 5 m 18 yr 11 m 7 yr 11 m 16 yr 4 m Lung at 5 yrs 8 yr 1 m 13 yr 4 m 4 yr 8 m 6 yr 10 m 16 yr 3 m 14 yr 9 yr 1 m 5 yr 9 m 5 yr 5 m 4 yr 3 m

Outcome ANED ANED ANED ANED ANED DWED ANED ANED ANED ANED ANED DNED DNED ANED ANED

ANED: Alive and no evidence of disease. DNED: Dead with no evidence of disease. DWED: Dead with evidence of disease. * Chemotherapy. ** Radiotherapy unknown.

Results The actuarial survival figures are 100% at 5 years and 62% at 10 a n d 15 years (Fig. 1). The disease-specific survival is 100% at 5 years and 86% at 10 a n d 15 years. There have been no local or regional recurrences. One patient developed lung metastases at 5 years a n d died 8 years after treatment. Two patients have died o f unrelated disease, with no evidence o f recurrent or distant disease, a l t h o u g h autopsies were n o t obtained. Histological typing revealed 1 solid, 9 c r i b r i f o r m and 5 tubular p a t t e r n tu-

100 90

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80 >

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mours. The excision m a r g i n s were n o t clear o f microscopic disease in 9 o f the 15 patients. There was invasion o f a n a m e d nerve in 9 cases and vascular invasion in 2.

Discussion C u r r e n t m a n a g e m e n t concepts favour c o m b i n e d t r e a t m e n t rather t h a n supraradical surgery. C o m b i n a t i o n treatment with b o t h surgery a n d r a d i o t h e r a p y has improved the control o f local disease but n o t necessarily survival 1'3 8,10 12,14 However, the indications for radiotherapy often d e p e n d on putative prog-

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60 50 40 30 L)

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Death 1 -- Relapse~

20 10 0

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5

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10

15

20

T i m e post operation (years)

Fig. 1. Kaplan-Meier actuarial survival curve. Actuarial survival is 100% at 5 years, 62% at 10 and 15 years. Disease-specific survival is 100% at 5 years and 86% at 10 and 15 years.

nostic indicators and a variety o f radiotherapy regimens have been used. The m a i n prognostic indicators are t u m o u r site, stage, histological type, microscopic or gross disease at the surgical m a r g i n a n d perineural or perivascular invasion1-12,14,16. FORDICE et al. 3 recently r e p o r t e d a large series o f 140 patients with a d e n o i d cystic carcinoma o f the h e a d a n d neck treated with surgery and postoperative r a d i o t h e r a p y over a 20-year p e r i o d at the D e p a r t m e n t o f H e a d and N e c k Surgery at the M. D. A n d e r s o n Cancer Centre. Loc0-regional control was achieved in 85% o f patients a n d diseasespecific survival at 5, 10 and 15 years was 89%, 67.4% a n d 39.6%, respectively. Perineural invasion o f a n a m e d nerve, positive surgical m a r g i n s a n d tum o u r s with solid p a t t e r n histology were associated with an increased rate o f t r e a t m e n t failure. Multiple presenting s y m p t o m s , positive l y m p h nodes, perineural invasion o f a n a m e d nerve and t u m o u r s with solid p a t t e r n histology were associated with increased m o r tality. There were n o specific indicators o f isolated loco-regional recurrence. GARDEN et al. 4 have also r e p o r t e d an earlier series o f 198 patients f r o m the D e p a r t m e n t o f R a d i o t h e r a p y at the M. D. A n d e r s o n Cancer Centre treated with c o m b i n e d surgery and p o s t o p e r a tive r a d i o t h e r a p y over a 30-year period. In b o t h o f these studies, r a d i o t h e r a p y was used for all cases except small lowgrade lesions with clear m a r g i n s a n d n o perineural invasion. Local control was

Combined treatment o f adenoid cystic carcinoma o f salivary glands achieved in 95%, 86% and 79% at 5, 10 and 15 years, respectively. Local recurrence was significantly higher with positive resection margins and perineural invasion of a named nerve. Both FORDICE et al. 3 and GARDEN et al. 4 found that positive margins did not influence survival. Distant metastases were the c o m m o n e s t type of recurrent disease. The current study is the first to present the experience of a single surgeon using wide local excision combined with radical postoperative radiotherapy for all patients regardless of prognostic indicators. To date no local recurrences have occurred and the survival figures compare favourably with the published data. A contributory factor may be that all of the cases treated were new prim a r y tumours and only one had a solid histological pattern. However, the majority also had perineural invasion of a named nerve (9/15) and one-third were stage 4 disease; these latter factors have been associated with increased treatment failure 3,4,14. FOP.DICE et al. 3 and others 5,7,9 have noted increased local recurrence and decreased survival with a solid histological pattern, but this has not been supported by other investigators 1,s,11,14. The m e a n follow-up in the current series is 9 years, but most local recurrences occur within 10 years of treatment 1,11,14-16. We have been unable to identify prognostic indicators in this series because there have been no loco-regional recurrences and the incidence of distant treatment failure is low. The results support the continued use of wide local excision and radical postoperative radiotherapy for the treatment of all adenoid cystic carcinomas regardless of prognostic factors.

Acknowledgments. Statistical analysis by Dr Richard Hooper, King's College School of Medicine and Dentistry, London.

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Address: Mr CME Avery Senior Registrar in Maxillofacial Surgery Queen Victoria Hospital East Grinstead West Sussex RH19 3DZ UK Tel." +44 1342 410210 e-maik chrisavery@ eastgrinsteaduk.freeserve, co. uk