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Clinical and oncological outcomes after surgical excision of parotid gland tumours in patients aged over 80 years
Int. J. Oral Maxillofac. Surg. 2013; 42: 1385–1390 http://dx.doi.org/10.1016/j.ijom.2013.06.010, available online at http://www.sciencedirect.com
Clinical Paper Head and Neck Oncology
Clinical and oncological outcomes after surgical excision of parotid gland tumours in § patients aged over 80 years
N. Fakhry1, B. Aldosari1, J. Michel1, R. Giorgi2,3, C. Collet1, L. Santini1, A. Giovanni1, P. Dessi1 1
Service d’ORL et de Chirurgie CervicoFaciale, Centre Hospitalier Universitaire La Timone, Marseille, France; 2LERTIM, AixMarseille Universite´, Faculte´ de Me´decine, Marseille, France; 3Service de Sante´ Publique et d’Information Me´dicale, Centre Hospitalier Universitaire La Timone, Marseille, France
N. Fakhry, B. Aldosari, J. Michel, R. Giorgi, C. Collet, L. Santini, A. Giovanni, P. Dessi: Clinical and oncological outcomes after surgical excision of parotid gland tumours in patients aged over 80 years. Int. J. Oral Maxillofac. Surg. 2013; 42: 1385– 1390. # 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The objective of this study was to evaluate the surgical and long-term outcomes of a series of patients aged over 80 years, operated on for parotid neoplasms. Among 614 parotidectomies for neoplasms performed between 1998 and 2008, 34 patients (5.5%) aged over 80 years were identified retrospectively. Pathological examination showed a malignant tumour in 24 and a benign tumour in 10 cases. Overall survival (OS) and disease-free survival (DFS) were determined by Kaplan–Meier analysis. A search for parameters that could influence the postoperative complication rate and long-term outcomes was carried out by univariate analysis. There was no postoperative death. Eight patients (24%) had postoperative complications. Malignant histopathology (P = 0.05) and radical resection (P = 0.033) were found to have a significant negative impact on the postoperative course. Focusing on malignant tumours, only histopathological type (metastasis vs primary tumour) was found to have a negative impact on OS. The 2and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05). Malignant or benign histopathology had no impact on OS. Our results showed acceptable clinical and long-term oncological outcomes in very elderly patients operated on for parotid tumours, including malignant tumours.
Introduction
Diseases affecting salivary glands include traumatic lesions, congenital diseases, and § This study was presented at the 118th annual meeting of the French ENT Society (SFORL), 15–17 October 2011, Paris, France.
0901-5027/01101385 + 06 $36.00/0
acute and chronic infections, as well as neoplastic lesions. Tumours of salivary glands are rare; they account for 0.4–6.5 cases per 100,000 persons per year and represent from 2% to 6.5% of neoplasms of the head and neck. They can occur in major salivary glands (90% cases) or in minor salivary glands (10% cases). The
Key words: surgery; cancer; age; elderly; salivary glands. Accepted for publication 20 June 2013 Available online 20 July 2013
parotid gland is by far the most frequently affected site, while the submandibular gland (9%) and sublingual glands (1%) are much less frequently involved. Malignant tumours of salivary glands represent 0.7% of all malignant tumours, approximately 3% of those affecting the head and neck, and 30% of all salivary neoplasms.
# 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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Malignant tumours of the parotid gland represent 1–3% of all tumours of the head and neck and constitute 70–80% of salivary gland tumours.1–3 The most recent proposals for classification have been submitted by the World Health Organization.4 Pleomorphic adenoma is the most frequent benign neoplasm of the salivary glands, representing between 45% and 80% of all salivary gland tumours, followed by Warthin’s tumour, which represents 10%. Among malignant tumours, mucoepidermoid carcinomas represent 30%, followed by adenoid cystic carcinomas (25%), carcinomas on pleomorphic adenoma (15%), and acinic cell carcinomas (5–10%). Tumours of the parotid gland are benign in 80% of cases, pleomorphic adenoma being the most common (80% of cases).2 It is well known that in the head and neck area, as in other human organs, malignant tumours become more frequent in old age. Likewise, tumours occurring in the parotid space increase during the last decades of life. This rise in incidence is particularly due to secondary parotid space neoplastic involvement from metastasis or primary tumours.5–7 The aim of this study was to evaluate surgical and long-term outcomes of a series of patients aged over 80 years, operated on for parotid neoplasms. Materials and methods Patients
Among 614 patients who underwent parotidectomy at our institution during the study period (1998–2008), 34 (5.5%) aged over 80 years were studied retrospectively. The mean age of these patients was 83.5 years (range 80–91 years). There were 23 males and 11 females (male to female sex ratio 2.1:1). Tumours were located in the left parotid in 18 cases and in the right parotid in 16 cases. Pathological examination showed a malignant tumour in 24 cases (71%): this was a primary tumour of the parotid gland in 11/24 cases and metastasis in 13/24 cases. Primary tumours were mucoepidermoid carcinoma in four, carcinoma ex-pleomorphic adenoma in two, basal cell carcinoma in two, sarcoma in one, and poorly differentiated carcinoma in two cases. Metastatic histopathological findings were: squamous cell carcinoma in 10, melanoma in one, Merkel cell carcinoma in one, and Hodgkin lymphoma in one case. Moreover, among malignant tumours, six patients were operated on for recurrent disease. In 10 cases the
Table 1. Characteristics of the study population. Number of patients Sex ratio Mean age (range) Cardiovascular problems Yes No ASA score ASA 2 ASA 3 Histology Malignant Benign Surgical technique Conservative surgery Radical surgery Neck dissection Yes No Postoperative complications Yes No
tumour was benign: pleomorphic adenoma in one, monomorphic adenoma in one, Warthin’s tumour in four, lipoma in one, inflammatory lesion in one, and benign cyst in two cases. The procedure consisted of a total parotidectomy with facial nerve dissection in 15 cases, radical parotidectomy in four, lateral parotidectomy in 10, and partial parotidectomy in five. Neck dissection was performed in 22 cases. Three patients initially treated at another institution had received preoperative radiotherapy and were treated surgically for a recurrence as salvage surgery. Thirteen patients received postoperative radiotherapy. Postoperative radiotherapy was discussed in all cases depending on the patient’s local and general conditions. Indications for postoperative radiotherapy were high-grade cancers, parotid metastases, and positive lymph nodes. The main characteristics of the patients are summarized in Table 1. All patients had received preoperative loco-regional and general work-ups to assess the feasibility of salvage surgery and to search for distant metastases. Moreover, all patients underwent a general health work-up including blood tests, vascular sonography, and cardiac checkup to assess the feasibility of general anaesthesia. All diagnostic and therapeutic decisions concerning patients in this study were taken at multidisciplinary meetings attended by teams representing head and neck surgery, medical oncology, radiation therapy, pathology, and radiology. This study had institutional review board approval.
34 23/11, M/F 83.5 years (80–91) 18 (53%) 16 (47%) 22 (65%) 12 (35%) 24 (71%) 10 (29%) 30 (88%) 4 (12%) 22 (65%) 12 (35%) 8 (24%) 26 (76%)
Main outcome measures
Overall survival (OS) and disease-free survival (DFS) were determined by Kaplan–Meier analysis. The impact on the postoperative complication rate of the following factors was analysed by univariate analysis: histopathology, radical surgery, lymph node surgery, radiotherapy, American Society of Anesthesiology (ASA) score, duration of general anaesthesia, and duration of hospital stay. The impact on patient outcomes (OS and DFS) of the following factors was investigated by univariate analysis: gender, co-morbidity using the ASA score, history of cardiovascular problems, duration of general anaesthesia, duration of hospital stay, postoperative complications, and histopathology. With regard to malignant tumours, the following factors were also analysed: metastases vs primary tumours, radical surgery vs limited surgery, lymph node surgery, preoperative or postoperative facial palsy, facial nerve resection, postoperative radiotherapy, and salvage surgery.
Statistical analysis
Categorical variables were described using numbers and proportions, and quantitative variables by the mean and standard deviation. Categorical variables were compared by Fisher’s exact probabilities test. OS and DFS were estimated by Kaplan–Meier analysis. Survival curves were compared using the log-rank test. The Cox model was used
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to study the effect of quantitative variables on the events considered. All statistical tests were performed with the R.2.13 software program for Windows, with a 5% threshold of significance. Results Morbidity and postoperative course
No postoperative death was observed. Eight patients (24%) had postoperative complications: two patients had unexpected temporary postoperative facial weakness after facial nerve dissection during conservative surgery, two had haematoma at the surgical site, and two patients had a postoperative local infection treated successfully with antibiotics. Moreover, two patients experienced Frey’s syndrome at the time of data collection. The average duration of general anaesthesia was 3 h 30 min (range 1 h 45 min to 4 h 45 min) and the mean hospital stay was 9 days (range 4–11 days). Regarding facial palsy, 10 patients (29%) presented with facial palsy during management: facial palsy was preoperative in three cases of malignant tumours due to a history of radiation therapy, previous surgery, or tumour recurrence, and was postoperative in seven cases. Postoperative palsies were due to nerve sacrifice during resection of malignant tumours in four cases and unexpected temporary facial palsy in three.
Fig. 1. Overall survival of the study population.
Long-term outcomes
After a median follow-up of 52 months (range 4–91 months), 12 patients (35%) had died. Among these patients, two died due to cancer recurrence: parotid melanoma metastasis in one and metastasis of cutaneous squamous cell carcinoma in the other. Of the remaining 10 patients, seven died of cardiac problems, one with pulmonary complications, one from stroke, and one from leukaemia. The mean time from surgery to death was 33 months (range 4–75 months). Six patients, all with a malignant pathology, experienced a recurrence. The median time between surgery and recurrence was 22 months. The 2- and 5-year OS rates were 77% and 52%, respectively (Fig. 1). The 2and 5-year DFS rates were 71% and 44%, respectively (Fig. 2). Predictors of postoperative complications
In our series, two variables were found to have a statistically significant negative
Fig. 2. Disease-free survival of the study population.
impact on the postoperative course. These were malignant histopathology (P = 0.05) and radical resection (P = 0.033). Other variables such as neck dissection (P = 0.17), ASA score (P = 0.21), duration of general anaesthesia (P = 0.26), duration of hospital stay (P = 0.97), and radiation therapy (P = 0.083) were not found to be significant as prognostic factors. Predictors of long-term outcomes
In our series, only the ASA score was found to have a statistically significant negative impact on OS. Indeed, 22 patients in our series had an ASA score of 2, and 12 had an ASA score of 3. Statistical analysis showed a worse prognosis of ASA 3 compared to ASA 2 (P = 0.05). Malignant or benign histopathology had no impact on OS (P = 0.79). The 2- and
5-year OS rates were 78% and 56%, respectively, for benign tumours, and 76% and 50%, respectively, for malignant tumours (Fig. 3). Sex (P = 0.13), cardiovascular history (seven patients were operated on under anticoagulation therapy due to cardiac problems and nine patients had hypertension under medication) (P = 0.47), duration of general anaesthesia (P = 0.66), duration of hospital stay (P = 0.10), and postoperative complications (P = 0.75) were not found to be significant prognostic factors (Table 2). Oncological outcomes
Focusing on malignant tumours, only histopathological type (metastasis or primary tumour) was found to have a statistically significant negative impact on OS, but not on DFS. The type of surgery (radical
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Fig. 3. Overall survival with malignant (blue) and benign tumours (red). The 2- and 5-year OS rates were 78% and 56%, respectively, for benign tumours, and 76% and 50%, respectively, for malignant tumours (P = 0.79).
Table 2. Impact of variables on overall survival and disease-free survival rates in the study population (P-value in univariate analysis). Variable
Overall survival rate
Malignant vs benign Sex Cardiac problems ASA score (2 vs 3) General anaesthesia duration Length of hospital stay Postoperative complications a
0.790 0.128 0.472 0.05a 0.664 0.103 0.746
Disease-free survival rate 0.347 0.55 0.527 0.05a 0.972 0.262 0.136
Statistically significant.
Table 3. Impact of variables on overall survival and disease-free survival rates in malignant tumours (P-value in univariate analysis). Variable
Overall survival rate
Metastasis vs primary Radical resection Lymph node dissection Postoperative complications Facial palsy Sacrifice of facial nerve Radiotherapy Recurrence a
a
0.05 0.179 0.176 0.746 0.903 0.203 0.733 0.703
Disease-free survival rate 0.282 0.604 0.708 0.136 0.254 0.473 0.859 0.824
Statistically significant.
surgery vs conservative surgery), lymph node dissection, facial palsy, facial nerve sacrifice, postoperative complications, radiotherapy, and recurrent disease were not found to be significant prognostic factors for either OS or DFS (Table 3). The 2- and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05, Fig. 4). The 2- and 5-year DFS rates were 64% and 64%, respectively, for primary tumours, and 67% and 25%, respectively, for metastasis (P = 0.28).
Discussion
The purpose of this study was to investigate the epidemiological criteria, therapeutic management, and outcome of patients over 80 years of age who underwent surgery for a tumour of the parotid gland. The parotid space is a relatively frequent site of swelling due to benign or malignant tumours. Benign neoplasms require surgical treatment in almost all cases. This consists of superficial parotidectomy or total parotidectomy, which
have no influence on survival but can cause small, often transient, functional problems. In contrast, malignant tumours may require more extensive surgery, such as radical parotidectomy with neck dissection and sometimes other procedures such as reconstructive surgery.2 It is well known that the survival of patients with malignant parotid tumours is dependent on the histotype and stage of the neoplasm, involvement of adjacent structures, and neck lymph node invasion, as well as on the patient’s general condition. The large number of subjects aged over 80 years in our series showed that parotid swellings, particularly due to malignant tumours, are relatively frequent in the last decades of life. It is known that malignant tumours of the parotid gland are more frequent in elderly than in young patients. According to the previous literature, these neoplasms are mostly secondary (intraparotid lymph node metastases), generally caused by cutaneous malignant tumours.3 It is important to point out that six patients in our series (25%) had recurrent malignant disease. All these patients were referred to our institution after initial treatment at another centre. In all cases, the initial treatment was suboptimal because of the age of the patient. Treatments were either limited surgery or radiotherapy without surgery. All patients were then referred for pain, bleeding, or facial palsy due to tumour recurrence. In all these cases, surgery was difficult to perform because of the tumour volume or preoperative radiation, and most required radical surgery. Another important point is the large number of facial palsies in our series. In three cases, patients had preoperative facial palsy mainly due to tumour recurrence. Four patients had nerve sacrifice during resection of the malignant tumours. These results highlight the need for rapid patient care. In numerous cases, the tumour was not treated because of the age of the patient, who was then referred to our institution following massive tumour evolution, pain, bleeding, or skin invasion. In cases of extirpable tumours and when patients were in good general condition, they required invasive surgery, but with poor postoperative outcomes. As we have shown, the preoperative workup is crucial, as the ASA score was the only factor influencing long-term patient survival. Interestingly, the prognosis of patients with malignant tumours was no worse than for patients with benign tumours. This could be related to the fact that survival in parotid gland tumours
Parotid surgery in patients aged over 80 years
Fig. 4. Overall survival with primary malignant tumours (blue) and metastasis (red). The 2- and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
should be studied over a longer period of time than in our study, which is not possible due to the age of the patient group. Thus, the most important criterion for patient selection should be the patient’s general condition and not tumour presentation (malignant or benign). Moreover, elderly patients often require more extensive preoperative and postoperative care than younger patients undergoing equivalent procedures. Finally, the life expectancy of these patients is not significantly different from the theoretical life expectancy of other patients of the same age.8–13 The management of parotid tumours in the very elderly is complex, as with other tumours of the head and neck. Passler et al. and Miccoli et al. previously studied surgical outcomes after thyroid surgery in elderly patients.14,15 Both showed a higher overall complication rate in elderly patients in their series. Moreover, a history of cardiovascular problems and ASA physical status were found to be the main risk factors for complications. In our series, only the ASA score was found to have a significant negative impact on OS. Others factors, including cardiovascular history, duration of general anaesthesia, and duration of hospital stay were not found to be significant prognostic factors. This can be explained by the fact that the ASA score is an overall assessment of the patient’s general condition. Moreover, all patients underwent a preoperative cardiac checkup to assess the feasibility of general anaesthesia, and surgery was contraindicated in patients with too severe cardiac problems.
In a study of 261 patients treated for head and neck cancer, Milet et al.16 compared postoperative outcomes of patients aged over 70 years (29/261) and younger patients (232/261). Variables evaluated were median length of stay, incidence of severe postoperative complications (surgical site infection, pneumonia, and infection caused by multi-resistant pathogens), and postoperative deaths. Their results showed that the postoperative course in elderly patients was not significantly different from that in younger patients. In another study, Nao et al.17 demonstrated the validity of ablative surgery and free flap reconstruction for elderly patients with oral or oropharyngeal cancer in terms of oncological and functional outcomes. Regarding our study, our results showed 2- and 5-year OS rates of 77% and 52%, respectively, which is acceptable given the age of the patients. Focusing on malignant tumours, only the histopathological type (metastasis vs primary tumour) was found to have a statistically significant negative impact on OS. Indeed, parotid metastases are the result of loco-regional tumour spread and our results are in agreement with those of previous reports.5–7 The type of surgery (radical surgery vs conservative surgery), lymph node dissection, facial palsy, facial nerve sacrifice, postoperative complications, radiotherapy, and recurrent disease were not found to be significant prognostic factors for either OS or DFS. According to the literature, surgery is the mainstay of treatment.18 Parotidectomy (total or superficial, with or without
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facial nerve preservation) is considered to be the best approach in order to achieve surgical resection with free margins.19,20 Cervical lymph node dissection is necessary in cases of clinical or radiological lymph node metastasis, and is systematic for some authors.21–24 The role of radiotherapy is becoming an important part of the treatment of parotid cancer, mostly as an adjuvant tool after surgical resection.8,25–27 In conclusion, our results showed good clinical and long-term oncological outcomes in very elderly patients operated on for parotid tumours, including malignant tumours. The management of parotid tumours in these patients remains difficult and requires a multidisciplinary approach. It should be noted that our study focused only on surgical and oncological outcomes, but not on quality of life. Further studies including patient quality of life before and after surgery should be performed in order to better select patients eligible for such procedures. Funding
None. Competing interests
None. Ethical approval
None. References 1. Dorairajan N, Periyasamy S, Muthayya P, Manikandan R, Srinivasan T, Siddharth D. Salivary gland tumors: a 10-year retrospective study of survival in relation to size, histopathological examination of the tumor, and nodal status. Int Surg 2004;89:140–9. 2. Luna MA. Pathology of tumors of the salivary glands. In: Thawley SE, Panje WR, Batsakis JG, Lindberg RD, editors. Comprehensive management of head and neck tumors. Philadelphia: WB Saunders Co; 1999. p. 1106–46. 3. Spiro RH. Salivary neoplasms: overview of a 35 year experience with 2807 patients. Head Neck Surg 1986;8:177–84. 4. Seifert G, Sobin LH. Histological typing of salivary gland tumours. World Health Organization International Histological Classification of Tumours. 2nd edition. New York: Springer; 1991. 5. Moore BA, Weber RS, Prieto V, El-Naggar A, Holsinger FC, Zhou X, et al. Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck. Laryngoscope 2005;115:1561–7.
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6. O’Brien CJ, McNeil EB, McMahon JD, Pathak I, Lauer CS, Jackson MA. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck 2002;24:417–22. 7. Croce A, D’Agostino L, Moretti A, Augurio A. Parotid surgery in patients over seventyfive years old. Acta Otorhinolaryngol Ital 2008;28:231–8. 8. Muravchik S. Pharmacological changes of aging. Proceedings of the 53rd ASA Annual Meeting, Refresher Course Lectures #19. ASA; 2002. p. 1–7. 9. Raymond R. Anesthetic management of the elderly patient. Proceedings of the 53rd ASA Annual Meeting, Refresher Course Lectures #321. 2002:1–7. 10. Warner D, Warner M. Anesthetic risk and the elderly. Syllabus on geriatric anesthesiology. ASA; 2002. p. 48–9. 11. Hosking MP, Warner MA, Lobdell CM, Offord KP, Melton 3rd LJ. Outcomes of surgery in patients 90 years of age and older. JAMA 1989;261:1909–15. 12. Liu L, Leung JM. Peri-operative complications in elderly patients. Syllabus on geriatric anesthesiology. ASA; 2002: 50–3. 13. Barnett SR. Pre-anesthetic evaluation for the elderly patient. Syllabus on geriatric anesthesiology. ASA; 2002: 54–5. 14. Passler C, Avanession R, Kaczirek K, Pragger G, Scheuba C, Niederle B. Thyroid surgery in geriatric patient. Arch Sur 2002;137:1243–8. 15. Miccoli P, Lacconi P, Cecchini PM, Caldarelli F, Ricci E, Berti P, et al. Thyroid surgery
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in patient aged over 80 years. Acta Chir Belg 1999;94:222–3. Milet PR, Mallet Y, El Bedoui S, Penel N, Servent V, Lefebvre JL. Head and neck cancer surgery in the elderly—does age influence the postoperative course? Oral Oncol 2010;46:92–5. Nao EE, Dassonville O, Poissonnet G, Chamorey E, Pierre CS, Riss JC, et al. Ablative surgery and free flap reconstruction for elderly patients with oral or oropharyngeal cancer: oncologic and functional outcomes. Acta Otolaryngol 2011;131:1104–9. Rutt AL, Hawkshaw MJ, Lurie D, Sataloff RT. Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 2011;90:174–84. John ME. Parotid cancer: a rational basis for treatment. Head Neck Surg 1980;3: 132–41. Day TA, Deveikis J, Gillespie MB, Joe JK, Ogretmen B, Osguthorpe JD, et al. Salivary gland neoplasms. Curr Treat Options Oncol 2004;5:11–26. Armstrong JG, Harrison LB, Thaler HT, Friedlander-Klar H, Fass DE, Zelefsky MJ, et al. The indications for elective treatment of the neck cancer of the major salivary glands. Cancer 1992;69:615–9. Regis De Brito Santos I, Kowalski LP, Cavalcante De Araujo V, Flavia Logullo A, Margin J. Multivariate analysis of risk factors for neck metastases in surgically treated parotid carcinomas. Arch Otolaryngol Head Neck Surg 2001;127:56–60. Frankenthalar RA, Byers RM, Luna M, Callender DL, Wolf P, Goepfert H. Predicting
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occult lymph node metastasis in parotid cancer. Arch Otolaryngol Head Neck Surg 1993;119:517–20. Terhaad CH, Lubsen H, Rasch CR, Levendag PC, Kaanders HH, Tjho-Heslinga RE, et al., Dutch Head and Neck Oncology Cooperative Group. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys 2005;61:103–11. Bell RB, Dierks EJ, Homer L, Potter BE. Management and outcome of patients with malignant salivary gland tumors. J Oral Maxillofac Surg 2005;63:917–28. Harrison LB, Armstrong JG, Spiro RH, Fass DE, Strong EW. Postoperative radiation therapy for major salivary gland malignancies. J Surg Oncol 1990;45:52–5. McNaney D, McNeese MD, Guillamondegui OM, Fletcher GH, Oswald MJ. Postoperative irradiation in malignant epithelial tumor of parotid. Int J Radiat Oncol Biol Phys 1983;9:1289–95.
Address: Nicolas Fakhry Service ORL et Chirurgie Cervico-Faciale Centre Hospitalier Universitaire la Timone Assistance Publique-Hoˆpitaux de Marseille/ Universite´ Aix–Marseille 264 rue Saint Pierre 13385 Marseille cedex 05 France Tel.: +33 4 91 38 60 71 fax: +33 4 91 38 77 57 E-mail: [email protected]
Clinical Paper Head and Neck Oncology
Clinical and oncological outcomes after surgical excision of parotid gland tumours in § patients aged over 80 years
N. Fakhry1, B. Aldosari1, J. Michel1, R. Giorgi2,3, C. Collet1, L. Santini1, A. Giovanni1, P. Dessi1 1
Service d’ORL et de Chirurgie CervicoFaciale, Centre Hospitalier Universitaire La Timone, Marseille, France; 2LERTIM, AixMarseille Universite´, Faculte´ de Me´decine, Marseille, France; 3Service de Sante´ Publique et d’Information Me´dicale, Centre Hospitalier Universitaire La Timone, Marseille, France
N. Fakhry, B. Aldosari, J. Michel, R. Giorgi, C. Collet, L. Santini, A. Giovanni, P. Dessi: Clinical and oncological outcomes after surgical excision of parotid gland tumours in patients aged over 80 years. Int. J. Oral Maxillofac. Surg. 2013; 42: 1385– 1390. # 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The objective of this study was to evaluate the surgical and long-term outcomes of a series of patients aged over 80 years, operated on for parotid neoplasms. Among 614 parotidectomies for neoplasms performed between 1998 and 2008, 34 patients (5.5%) aged over 80 years were identified retrospectively. Pathological examination showed a malignant tumour in 24 and a benign tumour in 10 cases. Overall survival (OS) and disease-free survival (DFS) were determined by Kaplan–Meier analysis. A search for parameters that could influence the postoperative complication rate and long-term outcomes was carried out by univariate analysis. There was no postoperative death. Eight patients (24%) had postoperative complications. Malignant histopathology (P = 0.05) and radical resection (P = 0.033) were found to have a significant negative impact on the postoperative course. Focusing on malignant tumours, only histopathological type (metastasis vs primary tumour) was found to have a negative impact on OS. The 2and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05). Malignant or benign histopathology had no impact on OS. Our results showed acceptable clinical and long-term oncological outcomes in very elderly patients operated on for parotid tumours, including malignant tumours.
Introduction
Diseases affecting salivary glands include traumatic lesions, congenital diseases, and § This study was presented at the 118th annual meeting of the French ENT Society (SFORL), 15–17 October 2011, Paris, France.
0901-5027/01101385 + 06 $36.00/0
acute and chronic infections, as well as neoplastic lesions. Tumours of salivary glands are rare; they account for 0.4–6.5 cases per 100,000 persons per year and represent from 2% to 6.5% of neoplasms of the head and neck. They can occur in major salivary glands (90% cases) or in minor salivary glands (10% cases). The
Key words: surgery; cancer; age; elderly; salivary glands. Accepted for publication 20 June 2013 Available online 20 July 2013
parotid gland is by far the most frequently affected site, while the submandibular gland (9%) and sublingual glands (1%) are much less frequently involved. Malignant tumours of salivary glands represent 0.7% of all malignant tumours, approximately 3% of those affecting the head and neck, and 30% of all salivary neoplasms.
# 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
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Malignant tumours of the parotid gland represent 1–3% of all tumours of the head and neck and constitute 70–80% of salivary gland tumours.1–3 The most recent proposals for classification have been submitted by the World Health Organization.4 Pleomorphic adenoma is the most frequent benign neoplasm of the salivary glands, representing between 45% and 80% of all salivary gland tumours, followed by Warthin’s tumour, which represents 10%. Among malignant tumours, mucoepidermoid carcinomas represent 30%, followed by adenoid cystic carcinomas (25%), carcinomas on pleomorphic adenoma (15%), and acinic cell carcinomas (5–10%). Tumours of the parotid gland are benign in 80% of cases, pleomorphic adenoma being the most common (80% of cases).2 It is well known that in the head and neck area, as in other human organs, malignant tumours become more frequent in old age. Likewise, tumours occurring in the parotid space increase during the last decades of life. This rise in incidence is particularly due to secondary parotid space neoplastic involvement from metastasis or primary tumours.5–7 The aim of this study was to evaluate surgical and long-term outcomes of a series of patients aged over 80 years, operated on for parotid neoplasms. Materials and methods Patients
Among 614 patients who underwent parotidectomy at our institution during the study period (1998–2008), 34 (5.5%) aged over 80 years were studied retrospectively. The mean age of these patients was 83.5 years (range 80–91 years). There were 23 males and 11 females (male to female sex ratio 2.1:1). Tumours were located in the left parotid in 18 cases and in the right parotid in 16 cases. Pathological examination showed a malignant tumour in 24 cases (71%): this was a primary tumour of the parotid gland in 11/24 cases and metastasis in 13/24 cases. Primary tumours were mucoepidermoid carcinoma in four, carcinoma ex-pleomorphic adenoma in two, basal cell carcinoma in two, sarcoma in one, and poorly differentiated carcinoma in two cases. Metastatic histopathological findings were: squamous cell carcinoma in 10, melanoma in one, Merkel cell carcinoma in one, and Hodgkin lymphoma in one case. Moreover, among malignant tumours, six patients were operated on for recurrent disease. In 10 cases the
Table 1. Characteristics of the study population. Number of patients Sex ratio Mean age (range) Cardiovascular problems Yes No ASA score ASA 2 ASA 3 Histology Malignant Benign Surgical technique Conservative surgery Radical surgery Neck dissection Yes No Postoperative complications Yes No
tumour was benign: pleomorphic adenoma in one, monomorphic adenoma in one, Warthin’s tumour in four, lipoma in one, inflammatory lesion in one, and benign cyst in two cases. The procedure consisted of a total parotidectomy with facial nerve dissection in 15 cases, radical parotidectomy in four, lateral parotidectomy in 10, and partial parotidectomy in five. Neck dissection was performed in 22 cases. Three patients initially treated at another institution had received preoperative radiotherapy and were treated surgically for a recurrence as salvage surgery. Thirteen patients received postoperative radiotherapy. Postoperative radiotherapy was discussed in all cases depending on the patient’s local and general conditions. Indications for postoperative radiotherapy were high-grade cancers, parotid metastases, and positive lymph nodes. The main characteristics of the patients are summarized in Table 1. All patients had received preoperative loco-regional and general work-ups to assess the feasibility of salvage surgery and to search for distant metastases. Moreover, all patients underwent a general health work-up including blood tests, vascular sonography, and cardiac checkup to assess the feasibility of general anaesthesia. All diagnostic and therapeutic decisions concerning patients in this study were taken at multidisciplinary meetings attended by teams representing head and neck surgery, medical oncology, radiation therapy, pathology, and radiology. This study had institutional review board approval.
34 23/11, M/F 83.5 years (80–91) 18 (53%) 16 (47%) 22 (65%) 12 (35%) 24 (71%) 10 (29%) 30 (88%) 4 (12%) 22 (65%) 12 (35%) 8 (24%) 26 (76%)
Main outcome measures
Overall survival (OS) and disease-free survival (DFS) were determined by Kaplan–Meier analysis. The impact on the postoperative complication rate of the following factors was analysed by univariate analysis: histopathology, radical surgery, lymph node surgery, radiotherapy, American Society of Anesthesiology (ASA) score, duration of general anaesthesia, and duration of hospital stay. The impact on patient outcomes (OS and DFS) of the following factors was investigated by univariate analysis: gender, co-morbidity using the ASA score, history of cardiovascular problems, duration of general anaesthesia, duration of hospital stay, postoperative complications, and histopathology. With regard to malignant tumours, the following factors were also analysed: metastases vs primary tumours, radical surgery vs limited surgery, lymph node surgery, preoperative or postoperative facial palsy, facial nerve resection, postoperative radiotherapy, and salvage surgery.
Statistical analysis
Categorical variables were described using numbers and proportions, and quantitative variables by the mean and standard deviation. Categorical variables were compared by Fisher’s exact probabilities test. OS and DFS were estimated by Kaplan–Meier analysis. Survival curves were compared using the log-rank test. The Cox model was used
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to study the effect of quantitative variables on the events considered. All statistical tests were performed with the R.2.13 software program for Windows, with a 5% threshold of significance. Results Morbidity and postoperative course
No postoperative death was observed. Eight patients (24%) had postoperative complications: two patients had unexpected temporary postoperative facial weakness after facial nerve dissection during conservative surgery, two had haematoma at the surgical site, and two patients had a postoperative local infection treated successfully with antibiotics. Moreover, two patients experienced Frey’s syndrome at the time of data collection. The average duration of general anaesthesia was 3 h 30 min (range 1 h 45 min to 4 h 45 min) and the mean hospital stay was 9 days (range 4–11 days). Regarding facial palsy, 10 patients (29%) presented with facial palsy during management: facial palsy was preoperative in three cases of malignant tumours due to a history of radiation therapy, previous surgery, or tumour recurrence, and was postoperative in seven cases. Postoperative palsies were due to nerve sacrifice during resection of malignant tumours in four cases and unexpected temporary facial palsy in three.
Fig. 1. Overall survival of the study population.
Long-term outcomes
After a median follow-up of 52 months (range 4–91 months), 12 patients (35%) had died. Among these patients, two died due to cancer recurrence: parotid melanoma metastasis in one and metastasis of cutaneous squamous cell carcinoma in the other. Of the remaining 10 patients, seven died of cardiac problems, one with pulmonary complications, one from stroke, and one from leukaemia. The mean time from surgery to death was 33 months (range 4–75 months). Six patients, all with a malignant pathology, experienced a recurrence. The median time between surgery and recurrence was 22 months. The 2- and 5-year OS rates were 77% and 52%, respectively (Fig. 1). The 2and 5-year DFS rates were 71% and 44%, respectively (Fig. 2). Predictors of postoperative complications
In our series, two variables were found to have a statistically significant negative
Fig. 2. Disease-free survival of the study population.
impact on the postoperative course. These were malignant histopathology (P = 0.05) and radical resection (P = 0.033). Other variables such as neck dissection (P = 0.17), ASA score (P = 0.21), duration of general anaesthesia (P = 0.26), duration of hospital stay (P = 0.97), and radiation therapy (P = 0.083) were not found to be significant as prognostic factors. Predictors of long-term outcomes
In our series, only the ASA score was found to have a statistically significant negative impact on OS. Indeed, 22 patients in our series had an ASA score of 2, and 12 had an ASA score of 3. Statistical analysis showed a worse prognosis of ASA 3 compared to ASA 2 (P = 0.05). Malignant or benign histopathology had no impact on OS (P = 0.79). The 2- and
5-year OS rates were 78% and 56%, respectively, for benign tumours, and 76% and 50%, respectively, for malignant tumours (Fig. 3). Sex (P = 0.13), cardiovascular history (seven patients were operated on under anticoagulation therapy due to cardiac problems and nine patients had hypertension under medication) (P = 0.47), duration of general anaesthesia (P = 0.66), duration of hospital stay (P = 0.10), and postoperative complications (P = 0.75) were not found to be significant prognostic factors (Table 2). Oncological outcomes
Focusing on malignant tumours, only histopathological type (metastasis or primary tumour) was found to have a statistically significant negative impact on OS, but not on DFS. The type of surgery (radical
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Fig. 3. Overall survival with malignant (blue) and benign tumours (red). The 2- and 5-year OS rates were 78% and 56%, respectively, for benign tumours, and 76% and 50%, respectively, for malignant tumours (P = 0.79).
Table 2. Impact of variables on overall survival and disease-free survival rates in the study population (P-value in univariate analysis). Variable
Overall survival rate
Malignant vs benign Sex Cardiac problems ASA score (2 vs 3) General anaesthesia duration Length of hospital stay Postoperative complications a
0.790 0.128 0.472 0.05a 0.664 0.103 0.746
Disease-free survival rate 0.347 0.55 0.527 0.05a 0.972 0.262 0.136
Statistically significant.
Table 3. Impact of variables on overall survival and disease-free survival rates in malignant tumours (P-value in univariate analysis). Variable
Overall survival rate
Metastasis vs primary Radical resection Lymph node dissection Postoperative complications Facial palsy Sacrifice of facial nerve Radiotherapy Recurrence a
a
0.05 0.179 0.176 0.746 0.903 0.203 0.733 0.703
Disease-free survival rate 0.282 0.604 0.708 0.136 0.254 0.473 0.859 0.824
Statistically significant.
surgery vs conservative surgery), lymph node dissection, facial palsy, facial nerve sacrifice, postoperative complications, radiotherapy, and recurrent disease were not found to be significant prognostic factors for either OS or DFS (Table 3). The 2- and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05, Fig. 4). The 2- and 5-year DFS rates were 64% and 64%, respectively, for primary tumours, and 67% and 25%, respectively, for metastasis (P = 0.28).
Discussion
The purpose of this study was to investigate the epidemiological criteria, therapeutic management, and outcome of patients over 80 years of age who underwent surgery for a tumour of the parotid gland. The parotid space is a relatively frequent site of swelling due to benign or malignant tumours. Benign neoplasms require surgical treatment in almost all cases. This consists of superficial parotidectomy or total parotidectomy, which
have no influence on survival but can cause small, often transient, functional problems. In contrast, malignant tumours may require more extensive surgery, such as radical parotidectomy with neck dissection and sometimes other procedures such as reconstructive surgery.2 It is well known that the survival of patients with malignant parotid tumours is dependent on the histotype and stage of the neoplasm, involvement of adjacent structures, and neck lymph node invasion, as well as on the patient’s general condition. The large number of subjects aged over 80 years in our series showed that parotid swellings, particularly due to malignant tumours, are relatively frequent in the last decades of life. It is known that malignant tumours of the parotid gland are more frequent in elderly than in young patients. According to the previous literature, these neoplasms are mostly secondary (intraparotid lymph node metastases), generally caused by cutaneous malignant tumours.3 It is important to point out that six patients in our series (25%) had recurrent malignant disease. All these patients were referred to our institution after initial treatment at another centre. In all cases, the initial treatment was suboptimal because of the age of the patient. Treatments were either limited surgery or radiotherapy without surgery. All patients were then referred for pain, bleeding, or facial palsy due to tumour recurrence. In all these cases, surgery was difficult to perform because of the tumour volume or preoperative radiation, and most required radical surgery. Another important point is the large number of facial palsies in our series. In three cases, patients had preoperative facial palsy mainly due to tumour recurrence. Four patients had nerve sacrifice during resection of the malignant tumours. These results highlight the need for rapid patient care. In numerous cases, the tumour was not treated because of the age of the patient, who was then referred to our institution following massive tumour evolution, pain, bleeding, or skin invasion. In cases of extirpable tumours and when patients were in good general condition, they required invasive surgery, but with poor postoperative outcomes. As we have shown, the preoperative workup is crucial, as the ASA score was the only factor influencing long-term patient survival. Interestingly, the prognosis of patients with malignant tumours was no worse than for patients with benign tumours. This could be related to the fact that survival in parotid gland tumours
Parotid surgery in patients aged over 80 years
Fig. 4. Overall survival with primary malignant tumours (blue) and metastasis (red). The 2- and 5-year OS rates were 86% and 86%, respectively, for primary tumours, and 67% and 29%, respectively, for metastasis (P = 0.05). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
should be studied over a longer period of time than in our study, which is not possible due to the age of the patient group. Thus, the most important criterion for patient selection should be the patient’s general condition and not tumour presentation (malignant or benign). Moreover, elderly patients often require more extensive preoperative and postoperative care than younger patients undergoing equivalent procedures. Finally, the life expectancy of these patients is not significantly different from the theoretical life expectancy of other patients of the same age.8–13 The management of parotid tumours in the very elderly is complex, as with other tumours of the head and neck. Passler et al. and Miccoli et al. previously studied surgical outcomes after thyroid surgery in elderly patients.14,15 Both showed a higher overall complication rate in elderly patients in their series. Moreover, a history of cardiovascular problems and ASA physical status were found to be the main risk factors for complications. In our series, only the ASA score was found to have a significant negative impact on OS. Others factors, including cardiovascular history, duration of general anaesthesia, and duration of hospital stay were not found to be significant prognostic factors. This can be explained by the fact that the ASA score is an overall assessment of the patient’s general condition. Moreover, all patients underwent a preoperative cardiac checkup to assess the feasibility of general anaesthesia, and surgery was contraindicated in patients with too severe cardiac problems.
In a study of 261 patients treated for head and neck cancer, Milet et al.16 compared postoperative outcomes of patients aged over 70 years (29/261) and younger patients (232/261). Variables evaluated were median length of stay, incidence of severe postoperative complications (surgical site infection, pneumonia, and infection caused by multi-resistant pathogens), and postoperative deaths. Their results showed that the postoperative course in elderly patients was not significantly different from that in younger patients. In another study, Nao et al.17 demonstrated the validity of ablative surgery and free flap reconstruction for elderly patients with oral or oropharyngeal cancer in terms of oncological and functional outcomes. Regarding our study, our results showed 2- and 5-year OS rates of 77% and 52%, respectively, which is acceptable given the age of the patients. Focusing on malignant tumours, only the histopathological type (metastasis vs primary tumour) was found to have a statistically significant negative impact on OS. Indeed, parotid metastases are the result of loco-regional tumour spread and our results are in agreement with those of previous reports.5–7 The type of surgery (radical surgery vs conservative surgery), lymph node dissection, facial palsy, facial nerve sacrifice, postoperative complications, radiotherapy, and recurrent disease were not found to be significant prognostic factors for either OS or DFS. According to the literature, surgery is the mainstay of treatment.18 Parotidectomy (total or superficial, with or without
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facial nerve preservation) is considered to be the best approach in order to achieve surgical resection with free margins.19,20 Cervical lymph node dissection is necessary in cases of clinical or radiological lymph node metastasis, and is systematic for some authors.21–24 The role of radiotherapy is becoming an important part of the treatment of parotid cancer, mostly as an adjuvant tool after surgical resection.8,25–27 In conclusion, our results showed good clinical and long-term oncological outcomes in very elderly patients operated on for parotid tumours, including malignant tumours. The management of parotid tumours in these patients remains difficult and requires a multidisciplinary approach. It should be noted that our study focused only on surgical and oncological outcomes, but not on quality of life. Further studies including patient quality of life before and after surgery should be performed in order to better select patients eligible for such procedures. Funding
None. Competing interests
None. Ethical approval
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Address: Nicolas Fakhry Service ORL et Chirurgie Cervico-Faciale Centre Hospitalier Universitaire la Timone Assistance Publique-Hoˆpitaux de Marseille/ Universite´ Aix–Marseille 264 rue Saint Pierre 13385 Marseille cedex 05 France Tel.: +33 4 91 38 60 71 fax: +33 4 91 38 77 57 E-mail: [email protected]