SEARCH

SEARCH BY CITATION

Keywords:

  • adenoid cystic;
  • adenoid;
  • adenoid cystic carcinoma;
  • salivary gland tumors;
  • head and neck cancer

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

BACKGROUND:

Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long-term prognosis continues to be guarded, with an estimated 10-year survival of <60%. Population-based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population-based data.

METHODS:

Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease-related categories.

RESULTS:

The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11-99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5-year, 10-year, and 15-year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison-specific log-rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65-0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71-0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36-3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37-0.54).

CONCLUSIONS:

The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation. Cancer 2012. © 2012 American Cancer Society


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

Adenoid cystic carcinoma (ACC) is a rare tumor that originates within secretory glands and accounts for a substantial portion of minor salivary, parotid, and submandibular gland malignancies.1, 2 Although this type of cancer typically arises within the salivary glands of the head and neck, other sites of origin include the ceruminous and lacrimal glands, as well as the excretory glands of the genital tract. The clinical behavior of ACC is unique among salivary gland tumors. It has been noted in the literature that ACC tumors progress slowly, typically with perineural extension3, 4; however, the exact biologic mechanisms and the life cycle of the disease are still poorly understood.

Due in large part to these knowledge gaps, as well as the relative scarcity of cases, nonsurgical treatment strategies for ACC have yet to be standardized. In an effort to more fully understand the course and behavior of the disease, many studies have focused on identifying specific prognostic factors for ACC. These indicators include site of origin,4 tumor size,5 advanced stage at diagnosis,4-7 distal metastases,5, 8 solid histological pattern,4, 8, 9 presence of tumors in lymph nodes,4, 10 and perineural invasion.1, 11

Currently, the most common course of treatment for ACC is surgical excision, which is typically followed by external radiation of the surgical bed and, in the head and neck, the draining of the named nerves.12-14 Microscopic ACC appears to be sensitive to radiotherapy, and the addition of postoperative radiotherapy has significant benefits for local control.8, 15, 16 Numerous phase 1 and 2 studies have been conducted to determine the efficacy of systemic therapies to manage nonresectable recurrences and metastasis. Both single-agent and combination chemotherapy regimens have been tested, with inconsistent results.13 Evidence from these studies for systemic single-agent therapies is strongest for platinum, 5-fluorouracil, and anthracyclines; combination chemotherapies using platinum, anthracyclines, and alkylating agent regimens seem to have the best overall response. Regardless, the noted duration of response with these traditional chemotherapy approaches has been reportedly short in a majority of cases—usually 5 to 13 months.5, 17-19 The use of intra-arterial chemotherapy has been disappointing.20

It has also been noted that ACC has a long natural history. To address this issue, the routine use of radiologic examinations, especially magnetic resonance imaging, in the postoperative period may help in the detection of recurrent disease from months to possibly years before they are clinically evident.21, 22

There has been an increased interest in molecularly targeted agents. A few have been tried and are currently being investigated in the setting of clinical trials. One such class of targeted agents includes the c-KIT inhibitor. c-KIT has a high expression rate in ACC, ranging from 78% to 100%.20, 23, 24 A better understanding of the biology and molecular pathogenesis of ACC will be crucial to the future success of targeted agents for this disease.

Population-based data pertaining to ACC of the head and neck (ACCHN) are scarce. Our goal was to assess the incidence and survival for patients diagnosed with ACCHN in the past 3 decades and to search for patterns suggestive of risk factors or factors that impact prognosis. By using data from a population-based cancer registry program, we analyzed ACCHN incidence according to various patient- and disease-related characteristics, and examined frequency and determinants of survival after diagnosis.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. SEER data collection began in the early 1970s and gradually expanded from the original 9 to the current 17 registries that now account for roughly a quarter of the US population. For the purpose of this study, SEER Historic Stage A was used in all analyses. To deal with multiple changes in disease staging over the years, all cases going back to the early 1970s are reclassified using a historic staging scheme that includes 3 relatively broad categories: localized, regional, and distal. Although we lose some of the staging detail with this approach, it allowed us to preserve data consistency across the 4 decades. The definitions of SEER historic stages are as follows25:

  • Localized cancer is cancer that is limited to the organ in which it began, without evidence of spreading.

  • Regional cancer is cancer that has spread beyond the original (primary) site to nearby lymph nodes or organs and tissues.

  • Distal cancer is cancer that has spread from the primary site to distant organs or distant lymph nodes.

  • Unstaged cancer is cancer for which there is not enough information to indicate a stage.

It is important to point out that some of the more recent categories of localized, regional, and distal disease may be classified differently in the historic SEER staging system. For example, the 2000 SEER Summary Staging Manual for tongue cancer (excluding base of tongue) indicates that localized tumors crossing the midline and tumors with mandibular and maxillary lymph node involvement currently considered as distal would be classified as regional according to the SEER historic staging system.26

We selected all cases coded as cancers of the oral cavity (including “lip,” “tongue,” “floor of mouth,” and “gum and other mouth”), pharynx and neck (including “tonsil,” “nasopharynx,” “oropharynx,” and “hypopharynx”), salivary glands, and other oral cavity and pharynx sites (not otherwise specified) with a microscopically confirmed histologic type of adenoid cystic carcinoma (M-8200/3) and a diagnosis made during 1973-2007. We focused on ACC of the aero-digestive tract in an effort to minimize heterogeneity in the study population. As behavior of this particular cancer is still poorly understood, we chose a priori to limit our analyses to sites that are considered part of the same organ system.

We examined temporal trends of ACCHN incidence rates (age-adjusted for US standard population) by sex, race, and stage at diagnosis. The race variable was dichotomized as white and black; other race categories were excluded from the analysis because of insufficient number of observations (274 total cases). Age at diagnosis was divided into tertiles at cutpoints of 50 years and 66 years as well as a dichotomous variable divided at the median age of 58 years. Lastly, marital status at the time of diagnosis was categorized as married and not-married (including never-married, widowed, divorced, and legally married but separated). Nearly all variables, with the exception of the survival time data, refer to a patients' status at diagnosis.

Results from the trend analyses were expressed as the average annual percentage change over the 35-year study period. Average annual percentage change was used to measure the change in incidence rates over time and was calculated by fitting a least squares regression line to the natural logarithm of the rates, using the calendar year as a regressor variable. Differences between trends for 2 time periods were tested for statistical significance by comparing the difference in regression coefficients divided by the standard error of that difference with a T distribution, with degrees of freedom defined as the sum of the years in both time periods minus 4.27

Observed survival (the proportion of patients surviving beyond a given interval) and relative survival (calculated by dividing the observed survival among cancer patients by the expected survival in the general population with the same age, race, and sex) were analyzed according to patient sex and race. This is not disease-specific survival. The 5-year, 10-year, and 15-year relative survival estimates were evaluated across 3 time periods: 1973-1982, 1983-1992, and 1993-2007. The follow-up data in survival analyses extended through the end of 2007. The crude survival analyses were based on Kaplan-Meier methods using a log-rank test of significance to assess the differences between curves. Multivariate analysis was performed using Cox proportional hazards models to evaluate the association between survival and potential risk factors after adjusting for all potential risk factors. The proportional hazards assumption was evaluated using graphical log(−log), time-dependent variable, and goodness of fit methods. If the proportional hazards assumption was violated, the adjusted associations were examined using extended Cox survival models. The results of these multivariate analyses were expressed as adjusted hazard ratios (HRs) accompanied by the corresponding 95% confidence intervals (CIs).

All data analyses were performed using SEER*Stat, Joinpoint (National Cancer Institute, Bethesda, Md), and SAS statistical software (SAS Institute, Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

A total of 3026 cases of ACCHN were reported to SEER between 1973 and 2007. The mean age at diagnosis was 57.4 years (range, 11-99 years), with 613 of these cases reported from 1973-1982, 639 cases from 1983-1992, 1009 cases from 1993-2002, and 765 cases from 2003-2007. As shown in Table 1, men and women represented 40.98% (n = 1240) and 59.02% (n = 1786) of the sample, respectively. The majority of cases were white (n = 2471; 81.66%), with blacks being the second largest group (n = 286; 9.45%). Patients with localized or regional disease accounted for 45.3% (n = 1372) and 36.38% (n = 1044), respectively, whereas 11.57% (n = 317) had distal metastases. Salivary gland primary tumors were the majority (57.98%), followed by oral cavity tumors including lip and oral tongue (36.91%), with oropharynx and nasopharynx accounting for 4.56% (Table 1).

Table 1. Characteristics of Adenoid Carcinoma Cases of the Head and Neck by Time Interval: SEER, 1973-2007
Case CharacteristicsAll Cases, N = 3026Time Interval
1973-1982, n = 6131983-1992, n = 6391993-2002, n = 10092003+, n = 765
No.%No.%No.%No.%No.%
  • Abbreviation: SEER, Surveillance, Epidemiology, and End Results.

  • a

    American Indian, Alaska Native, or unspecified.

  • b

    Using SEER Historic Stage A.

  • c

    Site recode: other oral cavity and pharynx.

Sex          
 Male124040.9823338.0126741.7843543.1130539.87
 Female178659.0238061.9937258.2257456.8946060.13
Race          
 White247181.6653787.6052782.4781180.3859677.91
 Black2869.45457.346610.33969.517910.33
 Asian or Pacific Islander2357.77243.92436.73898.827910.33
 Othera341.1271.1430.47131.29111.44
Stage          
 Localized137245.3432553.0229145.5444043.6131641.31
 Regional110136.3818229.6923436.6241140.7327435.82
 Distal35011.57558.97558.6110710.6013317.39
 Unstagedb2036.71518.32599.23515.05425.49
Site          
 Salivary gland175457.9634556.2833251.9659859.2747962.61
 Oral cavity111736.9123838.8326841.9435735.3825433.20
 Neck/pharynx1384.56284.57314.85484.76314.05
 Otherc170.5620.3381.2560.5910.13

Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflection points (Figs. 1-3). There were no significant differences of average annual percentage change by stage across any race- or sex-specific population subgroups. The decline was more apparent for localized ACCHN (average annual percentage change, −2.59) than for regional and distal disease (average annual percentage change, −1.07 and −1.94, respectively).

thumbnail image

Figure 1. Joinpoint analysis of adenoid cystic carcinoma of the head and neck incidence is shown by sex for all stages, Surveillance, Epidemiology, and End Results, 1973-2007.

Download figure to PowerPoint

thumbnail image

Figure 2. Joinpoint analysis of adenoid cystic carcinoma of the head and neck incidence is shown by race for all stages, Surveillance, Epidemiology, and End Results, 1973-2007.

Download figure to PowerPoint

thumbnail image

Figure 3. Joinpoint analysis of adenoid cystic carcinoma of the head and neck incidence is shown by stage for all cases, Surveillance, Epidemiology, and End Results, 1973-2007.

Download figure to PowerPoint

The overall 5-year, 10-year, and 15-year survival estimates for all stages among ACCHN patients were 90.34%, 79.88%, and 69.22%, respectively (Tables 2 and 3). As shown in Figure 4 the Kaplan-Meier survival curves differed significantly between men and women (log-rank, 45.64; P < .0001), with women having a better survival outcome. There were no significant differences in survival curves by race.

Table 2. Relative Survival of Adenoid Cystic Carcinoma of the Head and Neck by Time Interval and Sex: SEER, 1973-2007
All Cases1973-1982, n = 5661983-1992, n = 5891993+, n = 1555
RS95% Cum CIRS95% Cum CIRS95% Cum CI
60 months86.44%82.05%89.83%85.57%a81.32%a88.91%a82.48%a79.58%a85.01%a
120 months75.54%a69.96%a80.23%a74.13%a68.70%a78.76%a69.14%a64.39%a73.39%a
179 months66.62%60.14%72.29%66.68%a60.39%a72.20%a60.24%a52.46%a67.15%a
Males1973-1982, n = 2201983-1992, n = 2421993+, n = 649
RS95% Cum CIRS95% Cum CIRS95% Cum CI
60 months79.57%71.51%85.57%80.54%a73.24%a86.03%a79.90%a65.23%a54.10%a
120 months65.90%a56.35%a73.84%a68.30%a59.14%a75.83%a75.23%a57.70%a42.39%a
179 months54.02%43.63%63.30%58.93%a49.00%a67.57%a83.78%a71.75%a64.42%a
Females1973-1982, n = 3461983-1992, n = 3471993+, n = 906
RS95% Cum CIRS95% Cum CIRS95% Cum CI
  • Abbreviations: Cum CI, cumulative confidence interval; RS, relative survival; SEER, Surveillance, Epidemiology, and End Results.

  • The Kaplan-Meier method was used, with no adjustment for heterogeneity. Confidence interval: log(−log[]) transformation. A period of 179 months was used to approximate the 15-year relative survival to maintain an equal time interval for each decade using SEER data available during the study period (1973 to December 1987, 1983 to December 1997, and 1993 to December 2007).

  • a

    If the relative cumulative survival increased from a prior interval, it has been adjusted.

60 months90.35%a85.06%a93.83%a88.67%a83.27%a92.40%a84.23%a80.44%a87.35%a
120 months81.26%a74.15%a86.59%a77.63%a70.76%a83.07%a71.67%a65.27%a77.10%a
179 months73.87%65.46%80.53%71.23%a63.11%a77.88%a64.26%a53.83%a72.93%a
Table 3. Relative Survival of Adenoid Cystic Carcinoma of the Head and Neck by Time Interval and Race: SEER, 1973-2007
White1973-1982, n = 4941983-1992, n = 4811993+, n = 1216
RS95% Cum CIRS95% Cum CIRS95% Cum CI
60 months87.27%82.47%90.83%86.17%a81.38%a89.80%a82.40%79.04%85.27%
120 months76.17%a70.08%a81.19%a76.17%a70.04%a81.22%a70.02%a64.64%a74.75%a
179 months67.20%60.11%73.30%68.86%a61.71%a74.95%a60.42%a51.32%a68.35%a
Black1973-1982, n = 421983-1992, n = 641993+, n = 159
RS95% Cum CIRS95% Cum CIRS95% Cum CI
60 months81.40%a64.19%a90.89%a81.21%a65.54%a90.26%a85.23%a75.58%a91.28%a
120 months73.42%a50.91%a86.82%a66.33%a48.09%a79.43%a65.23%a49.33%a77.24%a
179 months66.45%a43.04%a82.03%a55.58%a36.37%a71.10%a56.24%a34.22%a73.43%a
Asian/Pacific Islander1973-1982, n = 231983-1992, n = 411993+, n = 157
RS95% Cum CIRS95% Cum CIRS95% Cum CI
  • Abbreviations: Cum CI, cumulative confidence interval; RS, relative survival; SEER, Surveillance, Epidemiology, and End Results.

  • The Kaplan-Meier method was used, with no adjustment for heterogeneity. Confidence interval: log(−log[]) transformation. A period of 179 months was used to approximate the 15-year relative survival to maintain an equal time interval for each decade using SEER data available during the study period (1973 to December 1987, 1983 to December 1997, and 1993 to December 2007).

  • a

    If the relative cumulative survival increased from a prior interval, it has been adjusted.

60 months73.41%a47.66%a87.90%a84.25%a66.17%a93.13%a78.47%a68.46%a85.63%a
120 months58.52%a32.88%a77.25%a62.32%a42.94%a76.76%a65.47%a49.97%a77.21%a
179 months41.74%a19.06%a63.10%a53.24%a34.04%a69.17%a65.47%a49.97%a77.21%a
thumbnail image

Figure 4. Kaplan-Meier survival curves are shown for sex for all stages, Surveillance, Epidemiology, and End Results, 1973-2007.

Download figure to PowerPoint

The multivariate analysis controlled for potential covariates, which included age, race, sex, stage at diagnosis, year of diagnosis, primary site, radiation therapy, and surgery of primary site. The proportional hazards assumption was not satisfied for age at diagnosis, and all further multivariate analyses were stratified on this variable using a no-interaction model. In addition, for the final model, the 3 stage categories were grouped as local/regional versus metastatic disease to facilitate clinical interpretation of results.

As shown in Table 4, the multivariate analyses revealed a better prognosis among women compared with men (HR, 0.73; 95% CI, 0.65-0.82) and among married individuals compared with a combined group that included never married, widowed, divorced, and separated patients (HR, 0.81; 95% CI, 0.71-0.91). It was also observed that more advanced stage of disease at diagnosis (HR, 2.79; 95% CI, 2.36-3.29) and primary tumor location in the neck/pharynx when compared with a primary site in the salivary glands (HR, 1.62; 95% CI, 1.25-2.01) were significant predictors of decreased survival. By contrast, patients with tumors originating in the oral cavity, again compared with those diagnosed with ACC of salivary glands (reference category), had a statistically significantly decreased HR of 0.86 (95% CI, 0.76-0.98). Lastly, surgical resection of the primary site (HR, 0.45; 95% CI, 0.37-0.54) was the only treatment variable shown to have a significant association with patient survival. The corresponding results for other covariates in the model, including radiation therapy, race, and year of diagnosis, did not show any significant departures from the null (Table 4).

Table 4. Multivariate Analysis: Adjusted Cox Proportional Hazard Model Evaluating Predictors of Survival in Adenoid Cystic Carcinoma of the Head and Neck Patients (Adjusted for Age)a
VariableCategoriesHR95% CI
  • Abbreviations: CI, confidence interval; HR, hazard ratio; ref, reference.

  • a

    HR for age is not reported because proportional hazards assumption for age was not met. The model was stratified by a median age at diagnosis of 58 years.

  • b

    Includes: single, widowed, separated, and divorced.

SexMale1.0 (ref)
Female0.730.650.82
StageLocal/regional1.0 (ref)
Distant metastasis2.792.363.29
Marital statusNot marriedb1.0 (ref)
Married0.810.710.91
Surgery of primary siteNo1.0 (ref)
Yes0.450.370.54
RaceWhite1.0 (ref)
Black1.110.911.35
Radiation therapyNo1.0 (ref)
Yes1.030.911.17
Site of primary tumorSalivary gland1.0 (ref)
Oral cavity0.860.760.98
Neck/pharynx1.621.252.01
Other1.490.713.15
Year of diagnosis1973-19821.0 (ref)
1982-20071.040.971.11

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

Our findings indicate that the overall incidence of ACCHN continues to decline, most notably in the less advanced stages of disease. This observation cannot be attributed to a change in the frequency of unstaged cases, which remained relatively stable over the study period. The decline in incidence may point to a change in certain environmental factors yet to be determined. Although it is noteworthy that salivary gland tumors, as a whole, include numerous histologic subtypes with a classification schema that has been updated many times, distinct incidence patterns also exist for each carcinoma depending on the histologic subtype.28 However, although changes in pathologic definition for different major salivary gland carcinomas subtypes would inevitably lead to changes in their observed incidence, the steady and progressive decline of incident ACCHN cases observed over several decades is not suggestive of this explanation alone. Subtypes of major salivary gland tumors, such as mucoepidermoid carcinomas, have been linked to environmental factors,29 but no such link has yet been reported for ACC. If such an environmental link is identified, it could plausibly explain observed incidence and survival outcomes through differential exposure.

Our observed survival data are consistent with the current literature that indicates a high rate of recurrent disease 5 years after the initial diagnosis. The long lag period from diagnosis and initial therapy until death in many cases is consistent with a chronic nature for this disease.

It is unclear why women and persons who are currently married tended to have better survival outcomes. The sex-specific survival differences raise the possibility that hormonal influences may be at play. In addition, it is plausible that women could be more apt to adhere to the treatment plan or tolerate the treatment, as would married rather than single patients. Although our analyses adjusted for stage, it is also possible that women and married persons are more likely to seek medical attention and therefore received an earlier diagnosis. All else equal, these findings suggest a need to more thoroughly look into possible sex differences in terms of biology and behavior of disease. The association between marital status and outcome is a well-described phenomenon reported across several cancer sites.30-32 Supportive care issues, timing of diagnosis, and adequate access to care may be affecting these results.

Similarly noted by other reviews as well as ours, adjuvant radiotherapy confers little survival advantage for this disease. As surgery of the primary site was the only demonstrated clinical intervention noted to confer a survival benefit for patients diagnosed with ACCHN, there is evidence for surgical therapy to remain the mainstay of therapy at the present. Conversely, one may argue that those patients who were surgically resectable (and therefore received treatment) had less advanced disease, did not have metastatic disease, or had fewer comorbidities because our measured survival was not cancer specific. Since the staging evaluation of our study depended on a crude grouping system provided by SEER, the surgical group may have included a higher proportion of patients with resectable tumors. However, after controlling for disease stage, the association did not change and would tend to suggest otherwise. It is also possible that surgically treated patients had fewer comorbidities, a likely important variable that is not available in the SEER data and should be further considered in future population studies. Although, given the observed survival benefits, it is likely that surgery should remain the primary treatment option until more consistently successful radiation or systemic therapy methods are developed.

There has been only 1 other similar population-based study on survival trends in ACC, published by Lloyd and coauthors.33 Both the Lloyd study and ours concluded that sex plays a role in survival, and that postoperation radiation therapy does not significantly affect patient survival outcomes. However, the 2 studies meaningfully differ in their selection criteria and methods of analysis. The Lloyd data included cribriform histology and expanded the selection of primary sites to include skin primary sites of the head and neck, as well as upper respiratory tract (the nose, nasal cavity, middle ear, paranasal sinuses, and larynx) primary sites, the eye, and the thyroid gland. Although the larger sample size may have increased statistical power, the cases examined by Lloyd et al represent a more heterogeneous group of malignancies, with variable determinants of incidence and survival. In addition, our study included an examination of incidence rates for subpopulations based on sex, race, and stage of ACCHN, as well as a multivariate analysis using extended Cox models that included time-dependent variables.

A more comprehensive interpretation of study results requires understanding the strengths and limitations of SEER data. Disease registries such as SEER provide a large, reliable source of data with sufficient statistical power to examine even rare cancers such as ACC. Furthermore, population-based as opposed to institution-based studies have the added benefit of greater external validity. Conversely, our study is limited by the relatively limited number of variables and the level of detail available for each case. These limitations are particularly evident with regard to relevant clinical or treatment information. For this study, the lack of information about comorbidities, the type of surgery, and the chemotherapy and/or radiation therapies may preclude us from drawing more definitive conclusions. Another limitation of our analysis is the use of Historic Summary Stage A, which is less clinically relevant when compared with the staging adopted by the American Joint Committee on Cancer. To better understand the impact of this disease, larger prospective studies are needed to better assess prognostic factors and test novel treatment therapies.

In summary, the incidence of ACCHN appears to be on the decline across all study populations. As reported in the earlier literature, patient survival drops off considerably after 5 years and appears to change over time depending on patients' age and stage. Other factors that seem to affect ACCHN survival include sex, tumor site location, marital status, and surgery of the primary site. Additional research aimed at understanding the mechanisms underlying these observations is warranted.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES

No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. FUNDING SOURCES
  8. REFERENCES
  • 1
    Fordice J, Kershaw C, El-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg. 1999; 125: 149-152.
  • 2
    Spiro RH, Koss LG, Hajdu SI, Strong EW. Tumors of minor salivary origin. A clinicopathologic study of 492 cases. Cancer. 1973; 31: 117-129.
  • 3
    Huang M, Ma D, Sun K, Yu G, Guo C, Gao F. Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands. Int J Oral Maxillofac Surg. 1997; 26: 435-439.
  • 4
    Khafif A, Anavi Y, Haviv J, Fienmesser R, Calderon S, Marshak G. Adenoid cystic carcinoma of the salivary glands: a 20-year review with long-term follow-up. Ear Nose Throat J. 2005; 84: 662, 664-667.
  • 5
    Dodd RL, Slevin NJ. Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol. 2006; 42: 759-769.
  • 6
    Ciccolallo L, Licitra L, Cantu G, Gatta G; EUROCARE Working Group. Survival from salivary glands adenoid cystic carcinoma in European populations. Oral Oncol. 2009; 45: 669-674.
  • 7
    Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma: factors influencing survival. Am J Surg. 1979; 138: 579-583.
  • 8
    Matsuba HM, Simpson JR, Mauney M, Thawley SE. Adenoid cystic salivary gland carcinoma: a clinicopathologic correlation. Head Neck Surg. 1986; 8: 200-204.
  • 9
    Goepfert H, Luna MA, Lindberg RD, White AK. Malignant salivary gland tumors of the paranasal sinuses and nasal cavity. Arch Otolaryngol. 1983; 109: 662-668.
  • 10
    Perzin KH, Gullane P, Clairmont AC. Adenoid cystic carcinomas arising in salivary glands: a correlation of histologic features and clinical course. Cancer. 1978; 42: 265-282.
  • 11
    Vrielinck LJ, Ostyn F, van Damme B, van den Bogaert W, Fossion E. The significance of perineural spread in adenoid cystic carcinoma of the major and minor salivary glands. Int J Oral Maxillofac Surg. 1988; 17: 190-193.
  • 12
    Ghosal N, Mais K, Shenjere P, et al. Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma. Br J Oral Maxillofac Surg. 2011; 49: 510-515.
  • 13
    Ross PJ, Teoh EM, A'hern RP, et al. Epirubicin, cisplatin and protracted venous infusion 5-fluorouracil chemotherapy for advanced salivary adenoid cystic carcinoma. Clin Oncol (R Coll Radiol). 2009; 21: 311-314.
  • 14
    Wiseman SM, Popat SR, Rigual NR, et al. Adenoid cystic carcinoma of the paranasal sinuses or nasal cavity: a 40-year review of 35 cases. Ear Nose Throat J. 2002; 81: 510-514, 516-517.
  • 15
    Miglianico L, Eschwege F, Marandas P, Wibault P. Cervico-facial adenoid cystic carcinoma: study of 102 cases. Influence of radiation therapy. Int J Radiat Oncol Biol Phys. 1987; 13: 673-678.
  • 16
    Spiro RH. Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg. 1997; 174: 495-498.
  • 17
    Belani CP, Eisenberger MA, Gray WC. Preliminary experience with chemotherapy in advanced salivary gland neoplasms. Med Pediatr Oncol. 1988; 16: 197-202.
  • 18
    Licitra L, Cavina R, Grandi C, et al. Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol. 1996; 7: 640-642.
  • 19
    Tsukuda M, Kokatsu T, Ito K, Mochimatsu I, Kubota A, Sawaki S. Chemotherapy for recurrent adeno- and adenoidcystic carcinomas in the head and neck. J Cancer Res Clin Oncol. 1993; 119: 756-758.
  • 20
    Le Tourneau C, Razak AR, Levy C, et al. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland. Br J Ophthalmol. 2011; 95: 1483-1489.
  • 21
    Prokopakis EP, Snyderman CH, Hanna EY, Carrau RL, Johnson JT, D'Amico F. Risk factors for local recurrence of adenoid cystic carcinoma: the role of postoperative radiation therapy. Am J Otolaryngol. 1999; 20: 281-286.
  • 22
    Rosai J. Major and minor salivary gland tumors. In: Rosai J, ed. Rosai and Ackerman's Surgical Pathology. 9th ed. London: Mosby; 2004: 873-917.
  • 23
    Locati LD, Perrone F, Losa M, et al. Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs). Oral Oncol. 2009; 45: 986-990.
  • 24
    Vila L, Liu H, Al-Quran SZ, Coco DP, Dong HJ, Liu C. Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Mod Pathol. 2009; 22: 1296-1302.
  • 25
    Surveillance Epidemiology and End Results Program. Glossary of statistical terms. Updated January 28, 2011. Available at: http://www.seer.cancer.gov/cgi-bin/glossary/glossary.pl#glossary-27 Accessed March 2010.
  • 26
    Young JL Jr, Roffers SD, Ries LAG, Fritz AG, Hurlbut AA, eds. SEER Summary Staging Manual 2000: Codes and Coding Instructions. Bethesda, MD: National Cancer Institute; 2001.
  • 27
    Kleinbaum DG, Kupper LL, Muller KE. Applied Regression Analysis and Other Multivariable Methods. 2nd ed. Boston, MA: PWS-Kent; 1988.
  • 28
    Boukheris H, Curtis RE, Land CE, Dores GM. Incidence of carcinoma of the major salivary glands according to the WHO classification, 1992 to 2006: a population-based study in the United States. Cancer Epidemiol Biomarkers Prev. 2009; 18: 2899-2906.
  • 29
    Land CE, Saku T, Hayashi Y, et al. Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk. Radiat Res. 1996; 146: 28-36.
  • 30
    Abern MR, Dude AM, Coogan CL. Marital status independently predicts testis cancer survival—an analysis of the SEER database. Urol Oncol. [published online ahead of print September 25, 2010.]
  • 31
    Johnson TV, Master VA. Decreased cancer survival in individuals separated at time of diagnosis: critical period for cancer pathophysiology? Cancer. 2010; 116: 5564; author reply 5564.
  • 32
    Wang L, Wilson SE, Steward DB, Hollenbeak CS. Marital status and colon cancer outcomes in US Surveillance, Epidemiology and End Results registries: does marriage affect cancer survival by gender and stage? Cancer Epidemiol. 2011; 35: 417-422.
  • 33
    Lloyd S, Yu JB, Wilson LD, Decker RH. Determinants and patterns of survival in adenoid cystic carcinoma of the head and neck, including an analysis of adjuvant radiation therapy. Am J Clin Oncol. 2011; 34: 76-81.