Analysis of Failure in Patients with Adenoid Cystic Carcinoma of the Head and Neck

Background: Adenoid cystic carcinoma (ACC) accounts for less than 1% of all head and neck malignancies. It is a locally aggressive tumor with a high prevalence of distant metastases. The current study aimed to identify independent predictors of outcome and to characterize the patterns of failure. Methods: This is an international retrospective clinicopathologic review of 495 ACC patients treated between 1985 and 2011 in 9 cancer centers worldwide. Results: Five-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) were 76%, 80% and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification and presence of distant metastases. Adjuvant treatment had no significant influence on outcome (p = 0.6). Advanced N stage (p = 0.004) age ≥70 years (p = 0.01) and bone invasion (p = 0.001) were associated with shorter DFS on multivariate analysis. Metastasis sites were: lung (20%), bone (4%), liver (3%) and brain (1%). Median time to diagnosis of distant metastasis was 30 months (range 2–192). Age ≥70 years, tumor site, orbital invasion and N stage were independent significant predictors of distant metastasis. Metastasis site had a significant impact on OS (p = 0.04) and DSS (p = 0.03). Conclusion: The clinical course of ACC was slow but persistent. Paranasal sinus origin was associated with the lowest distant metastasis rate but with the poorest outcome. We found no impact of adjuvant radiation or chemoradiation on outcome. These prognostic estimates should be taken into consideration when tailoring treatment for patients with ACC

Defining the surgical margins of adenoid cystic carcinoma and their impact on outcome: An international collaborative study

Background: The mainstay of treatment in adenoid cystic carcinoma (ACC) of the head and neck is surgical resection with negative margins. The purpose of this study was to define the margin status that associates with survival outcomes of ACC of the head and neck. Methods: We conducted univariate and multivariate analyses of international data. Results: Data of 507 patients with ACC of the head and neck were analyzed; negative margins defined as ≥5 mm were detected in 253 patients (50%). On multivariate analysis, the hazard ratios (HRs) of positive margin status were 2.68 (95% confidence interval [CI], 1.2–6.2; p =.04) and 2.63 (95% CI, 1.1–6.3; p =.03) for overall survival (OS) and disease-specific survival (DSS), respectively. Close margins had no significant impact on outcome, with HRs of 1.1 (95% CI, 0.4–3.0; p =.12) and 1.07 (95% CI, 0.3–3.4; p =.23) for OS and DSS, respectively, relative with negative margins. Conclusion: In head and neck ACC, positive margins are associated with the worst outcome. Negative or close margins are associated with improved outcome, regardless of the distance from the tumor. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1008–1014, 2017

Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinuses: A Meta-Analysis

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta-analysis of the literature and data from the International ACC Study Group. Setting University-affiliated medical center. Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p < 0.001). Perineural invasion and adjuvant treatment (radiotherapy or chemoradiation) were not associated with prognosis. Conclusion Tumor margin status and tumor site are associated with prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not. Adjuvant treatment apparently has no impact on outcome

The Significance of Close Margins on Outcome of Patients with Adenoid Cystic Carcinoma of the Skull Base: An International Collaborative Study

Background: The mainstay of treatment in adenoid cystic carcinoma (ACC) of the head and neck is surgical resection with negative margins. Surgical resection of skull base ACC might be limited by proximity to vital structures. The clinical significance of close margins (not involved but less than 5 mm) in ACC remains undefined. This study aims to characterize the impact of close margin on the outcome of patients with ACC of the skull base. Methods: Univariate and multivariate models were used to evaluate the clinical and pathologic data in an international collaborative study. Results: A total of 507 patients with ACC of the head and neck were analyzed. Of those, 108 (22%) had ACC of the paranasal sinuses and skull base. Negative margins were achieved in 38 (35%) patients with paranasal sinuses ACC compared with 49% and 57% in patients with major salivary glands and oral cavity ACC, respectively (p = .001). Close margins, were found in 16 patients (15%), with skull base ACC. Univariate analysis revealed that margin status was significant for 5 years overall survival (OS, p = .009) disease specific survival (DSS, p = .003) and disease free survival (DFS, p = .015) for patients with ACC of the skull base. Multivariate analysis in patients with ACC of the skull base, revealed that close margin status was a significant predictors for 5 years OS (HR-2.11, 95% CI, 1.3–4.2, p = .01), DSS (HR-2.1, 95% CI, 1.2–3. 1, p = .03) and DFS (HR-3.1, 95%CI, 1.3–8.2, p = .03). Conclusions: In patients with skull base ACC, close margins should be considered as an adverse pathological feature similar to positive margins

Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinuses: A Meta-Analysis

Objectives To identify independent predictors of outcome in patients with adenoid cystic carcinoma (ACC) of the paranasal sinuses and skull base. Design Meta-analysis of the literature and data from the International ACC Study Group. Setting University-affiliated medical center. Participants The study group consisted of 520 patients, 99 of them from the international cohort. The median follow-up period was 60 months (range, 32 to 100 months). Main Outcome Measures Overall survival (OS) and disease-specific survival (DSS). Results The 5-year OS and DSS of the entire cohort were 62% and 67%, respectively. The local recurrence rate was 36.6%, and the regional recurrence rate was 7%. Distant metastasis, most commonly present in the lung, was recorded in 106 patients (29.1%). In the international cohort, positive margins and ACC of the sphenoid or ethmoidal sinuses were significant predictors of outcome (p < 0.001). Perineural invasion and adjuvant treatment (radiotherapy or chemoradiation) were not associated with prognosis. Conclusion Tumor margin status and tumor site are associated with prognosis in ACC of the paranasal sinuses, whereas perineural invasion is not. Adjuvant treatment apparently has no impact on outcome

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study

Background Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. Methods ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. Findings Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. Interpretation Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. Funding None