Patterns of Recurrence and Survival of Adenoid Cystic Carcinoma of the Head and Neck After a Definitive Resection

Objective: To determine factors impacting recurrence and long-term survival of adenoid cystic carcinoma (ACC) of the head and neck after a definitive resection. Study design: Retrospective cohort study at an academic tertiary care hospital. Methods: Patients with ACC of the head and neck treated at our institution were reviewed. Those not receiving surgery, or with metastatic disease were excluded. Clinicopathological data on each patient was collected. Results: Of 113 patients identified with ACC, 99 were studied. The overall median survival for the cohort was 71 months (mean ± SD, 94 ±79 months). AJCC tumor stage and N stage were independent predictors of survival on multivariate analysis. Mean overall survival (p=.001) and time to recurrence (p=.006) were lower for patients with cervical lymph node positive disease (N+). Tumors in major salivary glands were associated with longer survival (p=.027). The overall recurrence rate was 53%, with a mean time to recurrence of 63 ± 64 months. The presence of lymphovascular invasion predicted recurrence on multivariate analysis (p=.002), with advanced tumor stage predicting early (≤36 months) recurrence (p=.013). Among the 57 patients who received adjuvant radiation therapy, there was no difference in survival, rate of recurrence, or time to recurrence, when compared to patients treated with surgery alone. Conclusions: Clinicopathological variables including AJCC tumor stage, tumor site, presence of N+ disease, and lymphovascular invasion may be used as prognostic factors in predicting survival and recurrence after a definitive resection of ACC of the head and neck. CONCLUSION INTRODUCTION RESULTS ACC is a rare malignant tumor of the major and minor salivary glands, accounting for 1% to 2% of all head and neck malignancies and approximately 10% of all salivary gland neoplasms.1 ACC exhibits extensive local tissue infiltration and perineural spread, which results in a high rate of recurrence despite aggressive surgical resection. Classically ACC has a distinct natural history characterized by slow and indolent growth, with late development of metastasis and often distant recurrence.3,4 Numerous studies have sought to determine clinicopathologic predictors of survival in patients with ACC. In general, tumors with perineural invasion, positive margins at surgery, cervical lymph node metastasis, solid histological features2, and distant metastasis3 are associated with increased treatment failures and recurrences. Since these tumors are rare and because they often present at an advanced stage some controversies exist as to the most appropriate treatment, yet, most sources agree that aggressive treatment of these tumors is necessary. Radiation therapy (RT), surgical resection, as well as combined modality treatments of these tumors have been reported.2,5-6 The purpose of the current study is to report a single institution’s experience with ACC of the head and neck, not only with the hope of further elucidating the relevant clinicopathological prognostic factors, but also to determine how surgical excision along with adjuvant treatment modalities for this rare malignancy affect the recurrence, time to recurrence, and long-term survival of these patients. Clinicopathological variables including AJCC tumor stage, tumor site, presence of N+ disease, and lymphovascular invasion may be used as prognostic factors in predicting survival and recurrence after a definitive resection of ACC of the head and neck. Because stage was an important predictor of final outcome, improvement in the disease detection in its early state should be encouraged in an effort to improve survival and recurrence of this rare salivary gland malignancy. Investigations at the molecular level may further clarify the distinct natural history and gender differences of this intriguing malignancy. Prospective randomized multicenter studies are needed to define the optimal treatment for ACC, with special regard to adjuvant treatment modalities. REFERENCES DISCUSSION ACC is a rare and obscure cancer characterized by a distinct natural history of slow indolent growth, and distant metastasis occurring as late as 1 to 2 decades after definitive treatment. The peculiar natural history of ACC is thought to be due to the tumor’s ability disseminate widely through submucosal and fibrous tissue planes around the primary tumor site, and extend via the perineural route through major and minor nerves. Over the last decade, many studies have focused on elucidating pretreatment factors that may serve as predictors of outcome in patients with ACC of head and neck. In the current series tumor stage was found to be a valuable prognostic factor in predicting not only the overall survival, but also early (≤36 months) cancer recurrence. Previous studies have indicated several histological features of ACC that may serve as prognostic factors. In the current series the presence of histological evidence of lymphovascular invasion was a not only a strong predictor of tumor recurrence, but was also associated with decreased overall survival. Perineural invasion was also associated with a higher incidence of recurrence. Tumors in major salivary glands were associated with longer survival compared to tumors of the oral cavity, sinonasal region, oropharynx, larynx, or external auditory canal. Interestingly, it was found that gender influenced the recurrence rate. Among those patients who had cancer recurrence 65% were women. The higher recurrence rate in women was not paralleled by lower survival. In fact, although not statistically significant, the average the survival for the female cohort was higher than for the males. These gender differences indicate that there may be a hormonal influence accounting for different forms and biological behaviors of ACC. The results of the current study support previous data that one of the biggest obstacles to cure of ACC is late development of distant metastasis. Forty-two percent of patients in this series with distant metastasis had no evidence of locoregional failure, with a mean time between the diagnosis of the primary lesion and the detection of distant metastasis of 59 months. STUDY POPULATION 0.195 51.0 ± 53.3 74.6 ± 80.3 63.0 ± 64.0 Time to recurrence (N=52) 31 (57.4%) 23 (42.6%) 54 (59.3%) + 0.088 14 (37.8%) 23 (62.2%) 37 (40.7%) Microscopic margin status (N=91) 0.686 30 (52.6%) 27 (47.4%) 57 (57.6%) Post-operative RT 0.024 19 (67.9%) 9 (32.1%) 28 (28.3) Lymphovascular invasion (N=66) 0.088 30 (51.7%) 28 (48.3%) 58 (58.6%) Perineural invasion (N=74) 0.44 15.2 ± 22.9 19.0 ± 19.5 17.2 ± 21.2 Duration of symptoms (months) N=77 13 (72.2%) 5 (27.8%) 18 (40.0%) 3 7 (70.0%) 3 (30.0%) 10 (22.2%) 2 0.023 5 (29.4%) 12 (70.6%) 17 (37.8%) 1 Grade (N=45) 14 (63.6%) 8 (36.4%) 22 (22.2%) IV 16 (84.2%) 3 (15.8%) 19 (19.2%) III 9 (32.1%) 19 (67.9%) 28 (28.3%) II 0.001 11 (36.7%) 19 (63.3%) 30 (30.3%) I Stage (N=99) 6 (85.7%) 1 (14.3%) 7 (7.00%) N+ 44 (47.8%) 48 (52.2%) 92 (93.0%) N0.112 N stage (N=99) 13 (61.9%) 8 (38.1%) 21 (21.2%) T4 16 (84.2%) 3 (15.8%) 19 (19.2%) T3 9 (33.3%) 18 (66.7%) 27 (27.3%) T2 0.002 12 (37.5%) 20 (62.5%) 32 (32.3%) T1 T stage (N=99) 0.84 27:23:00 28:21:00 55:44:00 Gender (F:M) 0.044 57.1 ± 15.5 50.7 ± 15.6 53.9 ± 17.8 Age at dx (years) P-value Deceased (N=50) Alive (N=49) All Patients (N=99) Variable 2.02-41.8 0.004* 0.001* 98 46 N Stage NN+ 0.586 0.023* 101 43 62 Tumor grade 1 2 3 0.081 0.002* 135 92 79 47 Cancer T stage T1 T2 T3 T4 0.051-0.318 0.008* 0.001* 136 97 80 45 AJCC tumor stage I II III IV 95% CI P-Value (Multivariate) P-Value (Univariate) Mean Survival (mo) Variable 1. Kim KH, Sung MW, Chung PS, et al. Adenoid cystic carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1994;120:721-26. 2. Fordice J, Kershaw C, El-Naggar A, et al. Adenoid cystic carcinoma of head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 1999;125:149-52. 3. Sung M, Kim KH, Kim J, et al. Clinicopathologic predictors and impact of distant metastasis from adenoid cystic carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2003;129:1193-7. 4. Rapidis AD, Givalos N, Gakiopoulou H, et al. Adenoid cystic carcinoma of the head and neck. Clinicophathological analysis of 23 patients and review of the literature. Oral Onc 2005;41:328-35. 5. Silverman DA, Carlson TP, Khuntia D, et al. Role of postoperative radiation therapy in adenoid cystic carcinoma of the head and neck. Laryngoscope 2004;114:1194-9. 6. Chen AM, Bucci MK, Weinberg V, et al. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiation Oncology Biol Phys 2006;66(1):152-9. Early (≤ 36 months) vs Late (>36 months) Recurrence 0 10 20 30 40 50 60 70 80 90 100