INCIDENCE AND SURVIVAL IN PATIENTS WITH SINONASAL CANCER: A HISTORICAL ANALYSIS OF POPULATION-BASED DATA

Transcription

1 ORIGINAL ARTICLE INCIDENCE AND SURVIVAL IN PATIENTS WITH SINONASAL CANCER: A HISTORICAL ANALYSIS OF POPULATION-BASED DATA Justin H. Turner, MD, PhD, Douglas D. Reh, MD Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. justin.turner@jhmi.edu Accepted 28 April 2011 Published online 24 August 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: /hed Abstract: Background. The present study uses populationbased data from the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the behavior of sinonasal tumors. Methods. Data for all sinonasal malignancies reported between 1973 and 2006 (n ¼ 6739) were extracted from the database. Time-dependent trends in incidence and survival were analyzed by linear regression. Results. The overall incidence of sinonasal cancer was cases per 100,000 population per year with a male:female ratio of 1.8:1. The most common histologies were squamous cell carcinoma (51.6%) and adenocarcinoma (12.6%), whereas the most common primary sites were the nasal cavity (43.9%) and maxillary sinus (35.9%). The incidence of sinonasal cancer remained relatively stable during the study period. No significant changes in overall relative survival were noted. The best relative survival was noted in patients treated with surgery or a combination of surgery and radiotherapy. Conclusions. The prognosis of patients with sinonasal cancer is generally poor, and has not changed substantially over the last 3 decades. VC 2011 Wiley Periodicals, Inc. Head Neck 34: , 2012 Keywords: cancer; carcinoma; sinonasal; nasal; sinus; SEER; population; incidence; survival Tumors of the nasal cavity and paranasal sinuses are rare, constituting <3% of upper aerodigestive tract malignancies, and <1% of all malignant tumors. 1 These lesions often present at a locally advanced stage and generally have a poor overall prognosis. 2,3 Sinonasal tumors are comprised of various histologies, including squamous cell carcinoma (SCC), adenocarcinoma, adenoid cystic carcinoma (ACC), melanoma, and esthesioneuroblastoma. Each of these specific neoplasms, in turn, is unique in its clinical behavior and aggressiveness, with overall 5- year survivals reported from 22% to 67%. 4 Because of their diversity and rarity, universally accepted treatment guidelines for sinonasal tumors have generally Correspondence to: J. H. Turner VC 2011 Wiley Periodicals, Inc. remained elusive. Most evidence comes from case series and/or limited studies, typically with relatively small sample sizes. As such, the relative roles of surgery, radiation, and chemotherapy in the treatment of these cancers have remained unclear. Furthermore, most studies to date have been performed at single institutions, meaning that conclusions from these individual groups may not be applicable to patient populations as a whole. As a group, the incidence of head and neck cancer has decreased over time, whereas survival has remained essentially stagnant. 5 Site-specific analysis has shown some notable differences when incidence, survival, and prognosis are compared. 6 However, no such studies exist for cancers of the nasal cavity and paranasal sinuses. In an effort to understand the clinical behavior of sinonasal malignancies and to gather data on trends in incidence and survival, we examined the Surveillance, Epidemiology and End Results (SEER) database, a population-based record managed by the National Cancer Institute (NCI). 7 We extracted all sinonasal malignancies reported to the database between 1973 and 2006 and performed analyses based on tumor histology, location, and demographic information. Trends in incidence and survival were examined over time, as were the results of different treatment therapies. By obtaining institution-independent data on these rare malignancies, this report seeks to guide clinical practitioners in establishing treatment protocols and counseling patients. PATIENTS AND METHODS The study population was extracted from the Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to The SEER program is a population-based incidence and survival database with information on all primary malignant tumors from various geographic areas. The registries making up the database have varied somewhat over time, but currently include 9 states (CA, CT, HI, IA, KY, LA, NJ, NM, UT), 6 metropolitan areas (Los Angeles, San Jose Monterey, San Francisco Oakland, Seattle Puget Trends in Sinonasal Cancer HEAD & NECK DOI /hed June

2 Sound, Atlanta, Detroit), rural Georgia, and the Native Alaska Tumor Registry, encompassing up to 26% of the U.S. population. Use of this de-identified dataset does not require Institutional Review Board approval. All primary malignant tumors of the nasal cavity (International Classification of Diseases for Oncology, 3rd edition [ICD-O-3] site code C30.0) and paranasal sinuses (C31.0, C31.1, C31.2, C31.3, C31.8, and C31.9) were extracted and used for subsequent analysis. Identified cases were grouped by histologic subcategory, and the most common subcategories (squamous cell carcinoma [SCC; ICD-O-3 histology code ], adenocarcinoma [ ], melanoma [ ], esthesioneuroblastoma [ ], adenoid cystic carcinoma [ACC, 8200/03], sinonasal undifferentiated carcinoma [SNUC, 8020/3]) were chosen for additional study. Frequencies, incidence rates, and relative survival were estimated using the SEER*Stat software (Surveillance Research Program, National Cancer Institute, 2010). 8 Rates were expressed per 100,000 persons and age-adjusted to the 2000 U.S. standard population. Relative survival rates were examined at 3-month intervals over a period of 5 years using the actuarial method. Relative survival was defined as the observed rate of survival adjusted to the expected survival rate of the U.S. population, matched to that demographic group and time period. Trends in incidence and survival were stratified by race, sex, and histology, and examined by linear regression analysis using the weighted linear least-squares method. Survival data were also compared after extracting data for stage of disease (localized, regional, distant) and treatment (radiation, surgery). Statistical analyses were performed with SEER*- Stat 6.6.2, Microsoft Excel (Redmond, WA), and GraphPad Prism software (La Jolla, CA). All statistical tests were 2-sided, with a statistical significance declared at a value of p.05. Comparison between survival curves was performed using the Z-test. 9 RESULTS Frequency of Sinonasal Tumors. Using the SEER registry limited use dataset for the years , a total of 6739 nonlymphoreticular malignancies from within the nasal cavity and accessory sinuses were identified (Table 1). Demographic analysis showed that most patients were diagnosed in the sixth decade or later (<55, 20.3%; 55 69, 42.1%; >70, 37.7%). A sizable majority of patients were male (3927, 58.3%) versus female (2812, 41.7%). By race, 82.2% were white, 9.0% were black, and 8.8% were classified as other. These lesions were composed mostly of tumors of epithelial origin, including SCC (3474, 51.6%), adenocarcinoma (848, 12.6%), esthesioneuroblastoma (426, 6.3%), and ACC (416, 6.2%). Other malignancies included melanoma (444, 6.6%) and SNUC (206, 3.1%), with various Table 1. Characteristics of sinonasal malignancies reported to the SEER database between 1973 and 2006 (n ¼ 6739). Characteristic No. (%) Age, y < (20.3) (42.1) > (37.7) Sex Male 3927 (58.3) Female 2812 (41.7) Race White 5540 (82.2) Black 604 (9.0) Other 595 (8.8) Histologic subtype Squamous cell 3474 (51.6) Adenocarcinoma 848 (12.6) Melanoma 444 (6.6) Esthesioneuroblastoma 426 (6.3) Adenoid cystic 416 (6.2) Undifferentiated 206 (3.1) Other 925 (13.7) Primary site Nasal cavity 2956 (43.9) Maxillary sinus 2421 (35.9) Ethmoid sinus 641 (9.5) Frontal sinus 73 (1.1) Sphenoid sinus 223 (3.3) Overlapping 173 (2.6) Not specified 252 (3.7) Abbreviation: SEER, Surveillance, Epidemiology, and End Results. pathologies representing the remaining tumors (925, 13.7%). Almost half of these lesions were localized to the nasal cavity (2956, 43.9%), with most others originating in the maxillary (2421, 35.9%) or ethmoid (641, 9.5%) sinus. Cancers of the frontal and sphenoid sinus were quite rare, comprising 1.1 and 3.3% of all sinonasal tumors, respectively. Trends in Incidence of Sinonasal Cancers. Historical trend analyses were performed for the most common sinonasal malignancies reported to the SEER database from 1973 to Sinonasal tumors in the histologic category other were excluded from subsequent calculations since this group is comprised of a heterogeneous group of tumors that could confound further data analyses. As shown in Figure 1, the rate of sinonasal malignancies per 100,000 population has remained relatively constant over the last 30þ years, with an overall incidence of cases per 100,000 population. Trend analysis suggested a slight decrease in the incidence of sinonasal tumors over time, although this difference did not reach statistical significance (annual percentage change [APC] ¼ 0.36%, p ¼.052) (Figure 1A). The incidence of sinonasal cancer among men and women was 0.71 and 0.39 cases per 100,000 population, respectively, corresponding to a male:female ratio of approximately 1.8:1. When analyzed by sex, a substantial decrease in the incidence of sinonasal cancer was noted in men 878 Trends in Sinonasal Cancer HEAD & NECK DOI /hed June 2012

3 Trends in Survival of Sinonasal Cancers. Survival data were extracted from the SEER database for the most common sinonasal malignancies and evaluated for trends in relative survival. Evaluation of relative survival was limited to the years 1973 to 2001, since 2001 was the last year for which 5-year survival data were available. Five-year relative survival during the study period was %. During that multidecade period, there was a trend toward improved survival over time, although that trend did not reach statistical significance (p ¼.054) (Figure 3A). Significant differences in relative survival were noted when patients were stratified by race, with white patients ( %) and patients of other races ( %) having substantially better survival compared with that of blacks ( %; p <.001) (Figure 3B). No differences were noted between men and women ( % vs %; p ¼.507) (Figure 3C). When evaluated by histologic subtype, no significant changes in survival were found for SCC (p ¼.130), melanoma (p ¼.358), SNUC (p ¼.193), ACC (p ¼.425), or esthesioneuroblastoma (p ¼.387) (Figure 4). Five-year relative survival for sinonasal adenocarcinoma showed significant improvement over the study period (p <.05). FIGURE 1. (A) Trends in incidence of sinonasal cancer from 1973 to (B) Trends in sex-specific incidence of sinonasal cancer. (C) Trends in race-specific incidence of sinonasal cancer. over time (APC ¼ 0.87%; p <.005), whereas no change was noted among women (p ¼.458) (Figure 1B). By race, incidence remained constant among whites (p ¼.265), with significant decreases among blacks (APC ¼ 1.13%; p <.05) and other races (APC ¼ 2.08%; p <.005) (Figure 1C). When analyzed by histologic subtype, significant increases in the incidence of melanoma (APC ¼þ3.08%; p <.001) and esthesioneuroblastoma (APC ¼þ2.41%; p <.001) were noted during the study period (see Figure 2). The incidence of SCC, by far the most common sinonasal malignancy, decreased substantially over the study period (APC ¼ 1.26%; p <.001). No significant differences were observed in the incidence of adenocarcinoma (p ¼.576), undifferentiated carcinoma (p ¼.138), or ACC (p ¼.459). Effect of Histology on Survival. The histologic subtypes that make up sinonasal malignancies are quite diverse and have variable clinical behaviors. We evaluated relative survival (RS) curves for the most common subtypes and found that cancers could be stratified into those with relatively good prognosis (esthesioneuroblastoma: 5-year RS %; ACC: %), relatively poor prognosis (melanoma: %; SNUC: %), and those with intermediate prognosis (SCC: %; adenocarcinoma: %) (Figure 5A). When analyzed by site of origin, similar 5-year survival was noted for tumors of the maxillary ( %), ethmoid ( %), sphenoid ( %), and frontal sinus ( %) (Figure 5B). In contrast, compared with cancer of the accessory sinuses, tumors originating in the nasal cavity had substantially improved survival ( %; p <.001 for comparison with all other subsites). Effects of Stage and Treatment on Survival. Due to changes in the staging classification system within the SEER database over time, standard TNM staging was not available during the entirety of the study. As an alternative, we extracted historical extent of disease data for sinonasal cancers, in which tumors are classified as having either localized, regional, or distant extension. Based on the current American Joint Committee on Cancer (AJCC) system, localized disease refers almost entirely to T1 lesions. Tumors can be classified as regional either due to regional metastasis or due to extension of tumor to surrounding Trends in Sinonasal Cancer HEAD & NECK DOI /hed June

4 FIGURE 2. Trends in histology-specific incidence of sinonasal cancer from 1973 to structures (ie, advanced T classification). Distant extension implies distant metastasis. Extent of disease data were available for 4035 tumors. At diagnosis, most sinonasal cancers had either regional (2199, 54.5%) or distant (602, 14.9%) extension, with a distinct minority having only local disease (1234, 30.6%). As shown in Figure 6A, survival is greatly influenced by extent of disease, with 5-year relative survival ranging from % for localized disease to 48.6% 1.3% and % for regional and distant disease, respectively (p <.001 between all groups). Specific TNM classification system data have been incorporated into the SEER database since To illustrate the approximate makeup of the dataset over the duration of the study, we gathered data on T classification for each extent of disease group from 2004 to As shown in Figure 6B, localized tumors are composed almost entirely of T1 lesions. Likewise, tumors with distant spread are composed almost entirely of T4 lesions. The regional disease group was more heterogeneous, although the vast majority showed advanced (T3/T4) T classification. During the entire study period, treatment data for radiation therapy (RT) were available for 5016 patients. All patients receiving therapeutic radiation other than beam radiation were excluded from the study. A majority of patients (3221, 64.2%) were treated with radiation; 1795 patients (35.8%) did not receive beam radiation. Five-year relative survival for those receiving and not receiving radiation was % and %, respectively (p <.001). When evaluated by extent of disease, radiation was associated with worse survival for patients with localized disease ( % 5-year RS for no RT; % for RT; p <.005) (Figure 6C). There was a trend 880 Trends in Sinonasal Cancer HEAD & NECK DOI /hed June 2012

5 radiation as a single modality compared with those receiving no treatment at all for both localized (p <.05), regional (p <.001), and distant disease (p <.001). For patients with regional disease, those receiving surgery (p <.001) and surgery with radiation (p <.001) had improved survival compared with those receiving only radiation. However, no survival benefit was noted with the addition of radiation to surgery (p ¼.720). Likewise, for patients with distant disease, those receiving surgery (p <.001) and surgery with radiation (p <.001) had improved survival compared with those receiving only radiation, with the addition of radiation to surgery providing additional survival benefit over surgery alone (p <.05). FIGURE 3. (A) Trends in 5-year relative survival of patients with sinonasal cancer between 1973 and (B) Race-specific survival of patients with sinonasal cancer. (C) Sex-specific survival of patients with sinonasal cancer. toward improved survival with RT in patients with regional disease (p ¼.053). In patients with distant disease, improved survival was noted for those treated with radiation ( % 5-year RS for RT; % for no RT; p <.001). Treatment data that recorded information on use of both surgery and/or radiation were available for 3794 patients. The vast majority received either surgery alone (1098, 28.9%) or surgery with radiation (1744, 46.0%). The remaining patients were treated with radiation alone (742, 19.6%) or received no treatment (210, 5.5%). For those patients with localized disease, surgery alone resulted in the best 5-year relative survival (Figure 6D). Combination therapy had a negative impact on survival compared with surgery alone (p <.005). Improved survival was observed in patients receiving DISCUSSION Sinonasal carcinoma is a relatively rare clinical entity, making assessment of trends in survival and treatment difficult or impossible. The SEER registries collectively pool population-based data from cancer patients throughout various regions of the United States, thus replicating the population as a whole. This allows for in-depth analysis of a large patient cohort, independent of individual or institutional biases. In general, there has been an overall decrease in the incidence of head and neck cancer during the last 3 decades, although remarkable variations exist between individual cancer subsites. 6,10 The current study found the overall incidence of sinonasal cancer between 1973 and 2006 to be cases per 100,000 population. This is in contrast to more common sites of head and neck cancer (oral cavity, salivary gland, oropharynx, larynx), where incidence may vary from 1 to 5 per 100,000 population. 6 Although the SEER data suggested a trend toward decreased incidence of sinonasal cancer over time, this trend was not statistically significant. Notably, we observed some interesting demographic patterns in time-specific incidence. For example, the incidence of sinonasal cancers has decreased significantly in men, while remaining stable or perhaps steadily increasing among women. Likewise, whereas the incidence of sinonasal cancer has remained stable in whites, dramatic decreases have been noted in other races, particularly blacks. These differences are consistent with findings in head and neck cancer as a whole and likely reflect changing demographics and socioeconomic developments that are beyond the scope of this article. 10 Cancers of the nasal cavity and paranasal sinuses are composed of diverse histologies with differing clinical characteristics. As reported here, more than 50% of malignant sinonasal tumors are SCCs, with other common diagnoses including adenocarcinoma, melanoma, ACC, SNUC, and esthesioneuroblastoma. This contrasts with a comprehensive literature review that examined more than 8000 patients with sinonasal malignancies reported over the last 20 years, in Trends in Sinonasal Cancer HEAD & NECK DOI /hed June

6 FIGURE 4. Trends in histology-specific survival of patients with sinonasal cancer between 1973 and which SCC represented only 36% of all reported tumors. 4 In contrast, a systematic review of the literature by Dulguerov et al, 11 examining more than 16,000 sinonasal malignancies reported from 1960 to 1998, found that 58% of all sinonasal tumors were SCCs, similar to our results. These differences, which are highly dependent on the period studied, likely represent the comparative commonality of adenocarcinoma in some European countries and an overall decline in squamous cell histologies over time. 4 In agreement with this hypothesis, we found that the incidence of sinonasal SCC has decreased over time, whereas the incidence of other cancers, including melanoma and esthesioneuroblastoma, has steadily increased. Whether the rates of these nonsquamous cell cancers have truly increased is debatable. There is a paucity of studies that have analyzed the trends in incidence of sinonasal melanomas and esthesioneuroblastomas Mucosal melanoma epidemiologic patterns differ from those of cutaneous melanoma, whose incidence has been increasing due to higher levels of sun exposure. Koomen et al 14 did show a nonsignificant increase in the incidence of ear, nose, and throat mucosal melanomas. Higher reported incidence of these histologies may be secondary to improved access to immunohistochemical techniques and better laboratory capabilities to differentiate between poorly differentiated malignancies. 15 Nonetheless, a change in the balance between histologies with relatively good prognosis and those with poor prognosis could conceivably contribute to the trend toward improved survival of patients with sinonasal cancer over time. Prior studies assert a steadily improving trend in oncologic results and/or survival for sinonasal cancer over the past few decades. 11,16 In a comprehensive 882 Trends in Sinonasal Cancer HEAD & NECK DOI /hed June 2012

7 FIGURE 5. (A) Histology-specific survival of patients with sinonasal cancer. (B) Site-specific survival of patients with sinonasal cancer. literature review of articles evaluating malignancies of the nasal and paranasal sinuses during the last 40 years, Dulguerov et al 11 noted some progress in the outcome and survival of patients during this time period. Average overall 5-year survival rates were reported at 28% in the 1960s and 51% in the 1990s. Our data show some incremental improvement that closely approaches statistical significance. This corresponds to a change in 5-year relative survival from approximately 49.7% for patients diagnosed in 1973 to 56.4% for those diagnosed in This is in agreement with pooled data showing improvement in overall survival from 40% to 47% for studies published before and after 2000, respectively. 4 This marginal improvement in survival is consistent with findings in other subsites, including nasopharynx, oropharyx, and hypopharynx. 6 When analyzed by histology, we also failed to show any statistically significant change in survival. The 1 exception, adenocarcinoma, demonstrated an improvement in relative 5-year survival corresponding to an increase from 49.6% in 1973 to 66.7% in This is in contrast to several other studies that have shown no improvement in survival for sinonasal adenocarcinoma over the last 2 to 3 decades. 11,18 Notably, the prognosis of adenocarcinoma of the nasal cavity and paranasal sinuses is highly FIGURE 6. (A) Stage-specific relative survival of patients with sinonasal cancer between 1973 and (B) Distribution of T classification (T1 T4) for patients with localized, regional, or distant disease between 2004 and (C) 5-year relative survival for patients treated with and without radiotherapy, compared by disease stage. (D) 5-year relative survival for patients with sinonasal cancer based on treatment modality and disease stage. Trends in Sinonasal Cancer HEAD & NECK DOI /hed June

8 dependent on tumor grade, with high-grade neoplasms having 3-year survival as low as 20%. 19 It is therefore conceivable that the improved survival noted for sinonasal adenocarcinoma in the United States may be secondary to a decline in the rate of high-grade intestinal variants of the disease often attributed to exposure to hardwood dust particles and other industrial contaminants. 17,20 In our analysis of the SEER database, almost half of all sinonasal cancers originated in the nasal cavity. The majority of remaining tumors originated from either the maxillary or ethmoid sinuses. This is in contrast to most published results in which the maxillary sinus was found to be the most common primary site. 4,11,21,22 Conversely, a nationwide survey in Denmark also found the nasal cavity to be the most common primary tumor site. 18 Interestingly, cancers of the nasal cavity have substantially better survival rates compared with those of the paranasal sinuses, likely secondary to earlier presentation of symptoms and, consequently, earlier diagnosis. Relative survival for paranasal sinus tumors was essentially independent of the specific sinus involved. When analyzed by histology, relatively good prognosis was observed for esthesioneuroblastoma, ACC, and adenocarcinoma, with 5-year relative survivals of 60% to 70%. The 5- year relative survival for patients with SCC was approximately 53%. Prognosis for patients with SNUC and melanoma was very poor, with 5-year relative survival in the range of 30% to 35%. These survival rates were consistent with several metaanalyses and large published case series. 4,11 As noted previously, the increased prevalence of sinonasal cancer in men compared with that in women has slowly disappeared over the last several decades. We found prognosis to be completely independent of sex. In contrast, although the incidence of sinonasal cancer has decreased substantially among minorities since the early 1970s, we noted significantly worse survival rates for patients identified by race as black. This difference likely reflects complex socioeconomic differences in access to care and medical follow-up. To our knowledge, this is the first study to highlight these contrasting demographic differences in incidence and survival for cancers of the nasal cavity and paranasal sinuses. A majority of patients analyzed through the SEER database had either regional or distant extension of their disease at presentation. Likewise, a review of 42 major reported series was published by Khademi et al, 4 in which almost 75% of patients presented with either stage III or stage IV disease. This factor is felt by many to be the major contributor to the poor prognosis of these cancers. We reaffirmed a substantial difference in survival between patients with localized, regional, and distant disease, with reported 5-year relative survivals of approximately 80%, 50%, and 30%, respectively. The treatment of sinonasal malignancies has yet to be standardized, limited in part by a lack of randomized controlled trials and adequately powered case series. Most cancers of the nasal cavity and paranasal sinuses present at later stages, often leading to the use of multimodality treatment. 2,3,23,24 Surgical therapy continues to be a mainstay for curative treatment, although the type of resection varies from purely endoscopic techniques to open surgery involving craniofacial resection with or without soft tissue reconstruction. In the current study, a majority of patients with sinonasal cancer received radiation as part of their treatment protocol. We found a reduction in relative survival for patients with localized disease receiving radiation. This finding is possibly due to bias in patient selection, since many patients who were treated with radiation alone could have had larger or more aggressive tumors and therefore were treated with palliative therapy. Although radiation was associated with a significant reduction in survival for patients with localized disease, apparent improvements were observed in patients with regional and/or distant disease. Despite separating patients by extent of disease, case-by-case differences certainly may result in the selection of one modality over another, and this certainly represents 1 of the limitations of this and other studies. We found that, in general, surgery was the most effective single-modality treatment for sinonasal cancer. Particularly in the case of localized disease, radiation either as a single modality or as part of combination treatment, offered limited survival advantage. This finding was in agreement with results from a large case series published by Blanch et al, 22 which found no survival benefit from the addition of radiotherapy to surgery for early-stage lesions. Conversely, for distant disease, radiation alone offered improved survival over no treatment at all, but also improved relative survival when added to surgery as a combination therapy. For regional disease, no improvement in survival was noted in patients treated with surgery and radiotherapy versus surgery alone. These findings are consistent with a published meta-analysis, which found 5-year survival rates of 33%, 70%, and 56%, for radiation, surgery, and combination surgery and radiotherapy, respectively, during the 1990s. However, as opposed to localized (mostly T1 lesions) and distant (mostly T4 lesions) disease, the regional dataset was a more heterogeneous population in terms of T classification. Although we did not show any statistically significant benefit of adding radiation to surgery for tumors with regional extension, some selection bias certainly exists within this group. Based on data since 2004, most patients with regional disease were treated with surgery and RT, although patients with T3/T4 disease were more than twice as likely to receive radiation in addition to surgery than patients with T1/2 disease. Thus as a group, those patients with larger and more aggressive lesions were likely treated with combination therapy or palliatively, rather than with surgery alone, and 884 Trends in Sinonasal Cancer HEAD & NECK DOI /hed June 2012

9 would consequently be expected to have reduced survival, regardless of therapy. The SEER database provides an unmatched sample size, with good follow-up that is independent of institutional-specific biases. However, some drawbacks to the use of these data do exist. As a national cancer database, the accuracy of recorded information is dependent on those individuals responsible for reporting the data. Errors in reporting may alter the data for individual patients and thus perturb the accuracy of the database as a whole. However, the effect of inaccurately recorded information is likely limited by dispersal of reporting among many authorized personnel throughout the United States. The data in the current study are also variable, by nature, with survival results attained from multiple institutions with different treatment algorithms. Furthermore, some data that would be useful for our analyses, including use of chemotherapy and status of surgical margins, are not recorded in the database. Despite some limitations, we were able to use the SEER database to evaluate the largest cohort of patients with sinonasal cancer to date. It is our anticipation that these data will provide insight into the clinical behavior and treatment of these tumors. CONCLUSIONS Sinonasal malignancies are a rare group of cancers that are generally associated with late presentation and poor prognosis. Few in-depth investigations into the behavior and treatment of these tumors exist in the literature. Using population-based data from the NCI SEER database, we were able to gather institution-independent data for over 6000 patients with sinonasal malignancies. We found that the incidence and survival of sinonasal cancer have remained relatively stable over the last 30 years, although significant demographic-dependent differences were noted over that time period. The prognosis of nasal and paranasal sinus malignancies is largely dependent on location, histology, and stage. The standard of care for the majority of these lesions continues to be surgery or surgery followed by adjuvant radiotherapy, with the use of radiation as a single modality offering questionable benefit. In the future, substantial improvements in prognosis will likely depend on the development of histology-specific directed treatments. REFERENCES 1. Silverberg E, Grant RN. Cancer statistics, CA Cancer J Clin 1970;20: Jakobsen MH, Larsen SK, Kirkegaard J, Hansen HS. Cancer of the nasal cavity and paranasal sinuses. Prognosis and outcome of treatment. Acta Oncol 1997;36: Sakata K, Aoki Y, Karasawa K, et al. Analysis of the results of combined therapy for maxillary carcinoma. Cancer 1993;71: Khademi B, Moradi A, Hoseini S, Mohammadianpanah M. Malignant neoplasms of the sinonasal tract: report of 71 patients and literature review and analysis. Oral Maxillofac Surg 2009; 13: Mao L, Hong WK, Papadimitrakopoulou VA. Focus on head and neck cancer. Cancer Cell 2004;5: Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005;114: Surveillance, Epidemiology, and End Results (SEER) Program ( SEER*Stat Database: Incidence SEER 17 Regs Research Data þ Hurricane Katrina Impacted Louisiana Cases, Nov 2008 Sub ( varying) - Linked To County Attributes: Total U.S., Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2009, based on the Month 2008 submission. 8. Surveillance Research Program, National Cancer Institute SEER*Stat software ( version Brown CC. The statistical comparison of relative survival rates. Biometrics 1983;39: Sikora AG, Toniolo P, DeLacure MD. The changing demographics of head and neck squamous cell carcinoma in the United States. Laryngoscope 2004;114: Dulguerov P, Jacobsen MS, Allal AS, Lehmann W, Calcaterra T. Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review. Cancer 2001;92: Chiu NT, Weinstock MA. Melanoma of oronasal mucosa. Population-based analysis of occurrence and mortality. Arch Otolaryngol Head Neck Surg 1996;122: McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of noncutaneous melanomas in the U.S. Cancer 2005;103: Koomen ER, de Vries E, van Kempen LC, et al. Epidemiology of extracutaneous melanoma in the Netherlands. Cancer Epidemiol Biomarkers Prev 2010;19: Lund VJ, Howard D, Wei W, Spittle M. Olfactory neuroblastoma: past, present, and future? Laryngoscope 2003;113: Ganly I, Patel SG, Singh B, et al. Craniofacial resection for malignant paranasal sinus tumors: report of an International Collaborative Study. Head Neck. 2005;27: Bussi M, Gervasio CF, Riontino E, et al. Study of ethmoidal mucosa in a population at occupational high risk of sinonasal adenocarcinoma. Acta Otolaryngol 2002;122: Grau C, Jakobsen MH, Harbo G, et al. Sino-nasal cancer in Denmark : a nationwide survey. Acta Oncol 2001;40: El Ayoubi A, Poizat F, Garrel R, et al. [Sinonasal adenocarcinomas reviewed. Prognostic value of WHO 2005 histological classification]. Ann Otolaryngol Chir Cervicofac 2009;126: Gordon I, Boffetta P, Demers PA. A case study comparing a meta-analysis and a pooled analysis of studies of sinonasal cancer among wood workers. Epidemiology 1998;9: Hoppe BS, Stegman LD, Zelefsky MJ, et al. Treatment of nasal cavity and paranasal sinus cancer with modern radiotherapy techniques in the postoperative setting: the MSKCC experience. Int J Radiat Oncol Biol Phys 2007;67: Blanch JL, Ruiz AM, Alos L, Traserra-Coderch J, Bernal-Sprekelsen M. Treatment of 125 sinonasal tumors: prognostic factors, outcome, and follow-up. Otolaryngol Head Neck Surg 2004;131: Harbo G, Grau C, Bundgaard T, et al. Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients. Acta Oncol 1997;36: Parsons JT, Mendenhall WM, Mancuso AA, Cassisi NJ, Million RR. Malignant tumors of the nasal cavity and ethmoid and sphenoid sinuses. Int J Radiat Oncol Biol Phys 1988;14: Trends in Sinonasal Cancer HEAD & NECK DOI /hed June