Prevalence and Survival Rate of Adenoid Cystic Carcinoma at Tygerberg Hospital

ABSTRACT
Introduction
Adenoid cystic carcinoma (ACC) is a rare malignant tumour of epithelial origin representing ten per cent of salivary gland tumours and one per cent of all head and neck malignant neoplasms. Despite its low prevalence, ACC is the most common malignant neoplasm of the submandibular and minor salivary glands (De Berardinis et al., 2018; Monteiro et al., 2013).
Due to the paucity of reports in the literature, very little is known about the prevalence and patient survival rate of ACC in sub-Saharan Africa. The poor long-term prognosis at 15 years could be attributed to the unpredictable behaviour of the malignancy, increased likelihood of recurrence and metastasis every five years; and poor understanding of the pathogenesis of the disease which hinders the development of new and standardised treatment regimens.
This study will raise awareness of ACC in South Africa, provide a better understanding of the complex pathogenesis, and identify potential risk factors implicated in the overall survival rate. This is the first prevalence study on ACC in South Africa. It provides a foundation for further research to improve the long-term prognosis of diagnosed ACC patients.
Aim
The aim of this study was to determine the prevalence and patient survival rate of ACC at
Tygerberg Hospital.
Materials and methods
A retrospective cohort study was performed. A search of the National Health Laboratory Service (NHLS) at Tygerberg Hospital was performed based on a Systemised Nomenclature of Medicine (SNOMED) code search for all histologically confirmed cases of ACC treated at Tygerberg Hospital over 27 years (1995 to 2022).
The data was collected from electronic pathology reports and medical records of diagnosed patients treated at Tygerberg Hospital. Clinicom was used to access patient follow-up visits. The status of the patient (alive or deceased) was confirmed by using the Department of Home Affairs’ status verification service through the Lexis® WinDeed website.
All data collected for this study was recorded on an Excel spreadsheet which was structured according to the objectives set out for the study.
The data recorded included a case reference number, the patient’s age in years at diagnosis, and sex. The treatment method was recorded as surgery with lymph node dissection, surgery without lymph node dissection, radiotherapy, chemotherapy, targeted agent, combination therapy, or no treatment. In the case where surgery was done, the presence of clear margins was determined. In the case of clear margins, presence, and time in months to local and/or distant recurrence were recorded. Different tumour parameters, such as tumour site, tumour size, lymph node involvement, presence of metastasis, histological type, and presence of perineural invasion (PNI) were recorded.
Overall survival rates at five, ten, and 15 years of ACC patients were compared with the different tumour parameters. The overall patient survival rate was calculated from the date of diagnosis to the date of death. For patients that did not have a date of death, the overall patient survival rate was calculated from the date of diagnosis to the date when the status verification was checked (3 November 2023). For patients who were not South African citizens or where no identification (ID) number was recorded, the overall patient survival rate was calculated from the date of diagnosis to the date of last seen as indicated on the Clinicom system.
Prevalence was reported over 27 years (1995 to 2022).
Results
A total of 40 ACC cases were included in the study and prevalence was reported as 1.04 cases per 100 000 population. The age of the patients at the time of diagnosis ranged from 16 to 84 years with a mean age of 53.40 years. Patients between the ages of 42 and 64 were most commonly affected (n = 21, 52.50%). Most patients were female (n = 23, 57.50%) and the male-to-female ratio was 1:1.4.
No local or distant recurrences were detected after surgical resection with clear margins.
Patients had a 50% probability of survival at five years and 25% at ten and 15 years.
Major salivary gland ACC had a better overall survival rate compared to minor salivary gland ACC (log-rank test p = 0.41). The overall survival of major salivary gland ACC was 65% at five years and 35% at ten and 15 years. The overall survival rate of minor salivary gland ACC was 50% at five years and 22.50% at ten and 15 years.
Regarding tumour size, T1 and T2 tumours had a better overall survival rate at five years with 82.50% compared to T3 and T4 tumours which had an overall five-year survival rate of 35% at five years. However, T1 and T2 tumours had a slightly worse overall survival rate at ten and 15 years (22.50%) when compared to the five- and ten-year overall survival rate of T3 and T4 tumours (27.50%) (log-rank test p = 0.09).
Patients with lymph node involvement had a poorer overall survival rate of 47.50% at five years and 22.50% at ten and 15 years compared to patients without lymph node involvement where an overall survival rate of 55% at five years and 25% at ten and 15 years was reported (log-rank test p = 0.51).
Patients who developed metastasis had a poorer overall survival rate compared to those who did not develop metastasis. The overall survival rate of patients who developed metastasis was 22.50% at five years and no patients survived past 2500 days (6.85 years). The overall survival for patients without the development of metastasis was much higher with 67.50% at five years and 32.50% at ten and 15 years. The presence of metastasis significantly impacted the overall survival rate as indicated by the log-rank test p-value of 0.04.
Patients without PNI had an overall survival rate of 85% at five, ten, and 15 years whereas patients with PNI had a lower overall survival rate of 42.50% at five years with no reported survival beyond 3500 days (9.60 years). Perineural invasion significantly impacted the overall survival rate as indicated by the log-rank test p-value of less than 0.01.
Dedifferentiated ACCs had the worst overall survival rate with no survival beyond 2.74 years. The cribriform subtype had a five-, ten- and 15-year overall survival rate of 45%. The mixed histological subtype had an overall survival rate of 60% at five years and 20% at ten and 15 years.
The solid histological subtype had the best overall survival rate at five years with 82.50% and an overall survival rate of 25% at ten and 15 years (Chi-square p-value: 10.63).
Due to the small sample size, a Kaplan-Meier graph illustrating the overall survival among the different treatment methods could not be calculated.
Conclusion
The prevalence rate of ACC was 1.04 cases per 100 000 population. An upward trend in the number of ACC cases was seen from 1995 to 2022 possibly due to improved reporting, unknown environmental factors, or in the case of ACC, an increase in the population of older people. Most differences seen between the overall patient survival rate and different tumour parameters were statistically insignificant. The presence of distant metastasis and PNI were the only tumour parameters that had a statistically significant impact on the overall patient survival rate but a bigger sample size is required to determine its true impact. Although the overall patient survival rate remained consistent at ten and 15 years due to the small sample size, there was a decrease in overall survival from five to ten years supporting the hypothesis that ACC has a poor long-term prognosis.
Although this study showed limited results due to a low-power dataset as in the case of many rare cancer research studies, it is the first ACC study done in South Africa. Thus, this study aims to form a foundation, spark interest, and possibly add value to future meta-analytic studies or systematic reviews involving the topic of ACC. The future of ACC research lies in the prevention of metastasis which will include an individualised approach, analysing each patient’s ACC genomic profile and implementing successful targeted treatment in addition to surgery and radiotherapy.