Determining the epidemiologic, outcome, and prognostic factors of ...

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ARTICLE 1

COVER STORY

Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database Robert J. Lee, DDS; Serena A. Lee, BS; Thomas Lin, DDS; Kevin K. Lee, BS; Russell E. Christensen, DDS, MS

O

ral malignant melanoma (OMM) is a rare tumor of neural crest–derived melanocytes in the basal layer of the oral mucous membrane.1-4 Primary mucosal melanomas of the head and neck are more rare than cutaneous melanomas and among those of the head and neck region, OMM constitutes 0.5% of oral neoplasms and 0.2% to 8% of all melanomas.1,3-10 OMM is highly aggressive and has a greater tendency to metastasize and invade the surrounding tissues than do other malignant tumors of the oral cavity.4 Eighty percent of OMMs arise in the mucosa of the maxilla, with the most common sites being the keratinizing mucosa of the hard palate and the alveolar gingiva.2,4,7-9,11-13 OMM occurs at a higher frequency in African Americans, the Japanese, and people from India, presumably because of the more common existence of melanin pigmentation in their oral mucosa.1,4 Unlike cutaneous melanomas, OMM has been reported overwhelmingly to occur more in males than females,1,2,4,5,7,10,11,14,15 with a male-tofemale ratio of approximately 3:1.4,7 However, Moore and Martin16 reported an almost equal OMM sex This article has an accompanying online continuing education activity available at: http://jada.ada.org/ce/home. Copyright ª 2017 American Dental Association. All rights reserved.

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ABSTRACT Background. The authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). Methods. The authors used the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). Results. The search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P ¼ .004; DSS, P ¼ .294), surgical resection (OS, P ¼ .046; DSS, P ¼ .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P ¼ .085). For confined and locally invasive disease, surgery (OS, P ¼ .001; DSS, P ¼ .004) and size (OS, P ¼ .154; DSS, P ¼ .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P ¼ .675; DSS, P ¼ .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P ¼ .049). Conclusions. Age at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. Practical Implications. Early and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES. Key Words. Cancer; epidemiology; mouth neoplasms; oral and maxillofacial disease; oral cancer. JADA 2017:148(5):288-297 http://dx.doi.org/10.1016/j.adaj.2017.01.019


TABLE 1 distribution, whereas investigators in other studies demonstrated a sex distribution with Patient demographic characteristics, tumor mostly females.17,18 characteristics, and treatment modality. No specific etiologic factors have been 1,4,19 Although investigators CHARACTERISTIC identified for OMM. PERCENTAGE OF PATIENTS have suggested that tobacco use, chronic irriAge, y tation from ill-fitting dentures, and alcohol < 50 16.8 consumption may play roles, evidence for their 50-69 37.5 correlation remains weak.2,11,12,19,20 ‡ 70 45.7 Clinically, OMM is typically asymptomatic Sex in the early stages, which may result in Male 47.8 delayed detection and account for the poor Female 52.2 prognosis of the disease.1,4 Patients with Race OMM have a reported 5-year survival rate White 79.3 from 10% to 25%, with a mean survival rate of African American 5.2 18.5 months.1,4 Because of the poor prognosis, Asian or Pacific Islander 8.6 especially in later stages of the disease, any Native American 3.9 pigmented lesion of uncertain origin should Other or unknown 3.0 be biopsied to rule out malignancy. Incisional Decade of Diagnosis biopsy remains the method of choice for 1970s 3.4 diagnosis.1,4 1980s 12.9 OMM exhibits aggressive behavior, vertical 1990s 13.4 growth pattern, high risk of developing metas2000s 70.3 4 tasis, and poor survival rates. In the early stages, Primary Site* patients with OMM may seek care for pigmented Lip 5.2 growths or swelling.4 In the later stages, common Tongue 9.1 symptoms include ulceration, bleeding, paresGingiva 30.6 4 thesia, and ill-fitting prostheses. OMM also may Floor of mouth 2.2 be detected in the later stages by the presence of Palate 39.2 pain, ulceration and hemorrhage of the overlying Buccal mucosa 9.5 epithelium, swelling, and loose teeth.1 OMM may Mouth, not otherwise specified 4.3 metastasize to regional lymph nodes, as well as Extent distant sites such as the lungs, liver, brain, and Localized 34.9 bone.1,2,4,11 Regional 33.6 Early diagnosis of OMM requires a thorDistant 16.4 ough review of the patient’s history, physical Unknown 15.1 examination, and examination of radiographic Tumor Size, Centimeters* and histopathologic features. The conventional < 2 28.4 therapy for OMM is surgical excision with 2-4 15.8 adequate negative margins and supplemental >4 7.3 radiotherapy.1,4 Adjunctive chemotherapy and Unknown 48.3 immunotherapy may be performed to miniSurgery Performed mize distant metastasis of the tumor.1 Yes 75.9 Chemotherapy, however, yields a low response No 24.1 rate.14 Although dacarbazine is used to treat Radiation Therapy cutaneous melanomas, it has no effect on Yes 31.5 OMM.21 When combined with interleukin-2, No 66.8 21,22 Other Unknown however, its effects may be beneficial. 1.7 immunotherapies are believed to reduce OMM * Percentages do not add up to 100% due to rounding. tumor size by activating killer T cells and inhibiting suppressor T cells.21 Recurrent OMM may develop 10 to 15 years after primary therapy,4 with more than one-half of all recurrences and meABBREVIATION KEY. DSS: Disease-specific survival. tastases occurring within 3 years.23 Presence of distant OMM: Oral malignant melanoma. OS: Overall survival. SEER: metastasis may be monitored by means of chest Surveillance Epidemiology, and End Results. SES: Socioecoradiography every 6 months after surgery.24 nomic status.

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1.0

1.0

0.8

0.8

CUMULATIVE SURVIVAL

CUMULATIVE SURVIVAL


0.6

0.4

0.2

0

0.4

0.2

0 0

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0.6

50

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300

SURVIVAL TIME (MONTHS)

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Figure 1. A. Kaplan-Meier estimates of overall survival for the entire cohort of patients. B. Kaplan-Meier estimates of disease-specific survival for the entire cohort of patients.

Investigators in a previous study using the population-based US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry found anatomic primary site was a statistically significant predictor of survival for patients with mucosal melanoma of the head and neck, with tumors in the nasal cavity and oral cavity allowing higher patient survival rates than do tumors in the nasopharynx and paranasal sinuses.25 This finding warranted a deeper examination of the oral cavity. The purpose of this study was to assess OMM in a larger population in terms of demographic characteristics, clinicopathologic features, treatment, and treatment outcomes. We used data from the SEER registry to analyze the patient and disease characteristics that determine overall survival (OS) and diseasespecific survival (DSS) after diagnosis. Although it was necessary to combine all various histologic codes for OMM in our study because of its low incidence, we believe that the factors affecting survival are not likely to vary for different OMM histologic subtypes. In this study, we also assessed socioeconomic factors obtained at the county level, including median family income, number of people below the federal poverty threshold, percentage of high school graduates, and unemployment rate. METHODS

We gathered data about patients with a diagnosis of OMM of the oral cavity from the US National Cancer Institute’s SEER registry (www.seer.cancer.gov). The


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SEER database encompasses 28.0% of the US population, which includes 25.6% of US African Americans, 38.4% of US Hispanics, and 20 different US geographic regions. Neither informed consent nor institutional review board approval was required for this study because the SEER database uses patient data that are publicly available and have been deidentified. Investigators in previous studies have validated the use of the SEER database for the analysis of OMM and oral cavity malignancies.25-27 We found 232 patients with OMM diagnosed in the SEER database during the period from 1973 to 2012. We used histologic codes from the International Classification of Diseases for Oncology, Third Edition,28 which included malignant melanoma, not otherwise specified (8720/3); nodular melanoma (8721/3); amelanotic melanoma (8730/3); superficial spreading melanoma (8743/3); desmoplastic melanoma, malignant (8745/3); and mucosal lentiginous melanoma (8746/3). Primary data extracted from the SEER database included the following: age at diagnosis, year at diagnosis, sex, race, histologic subtype, primary site, tumor extent and size from both collaborative stage and extent of disease coding methods, treatment with surgery, treatment with radiation, county socioeconomic status (SES), survival in months, and cause of death. The SEER database does not include information about when treatment was performed. The county SES variables extracted from these patients’ county of residence included median family income, unemployment rate, percentage of adults 25 years or older who had less than 12 years of education,


and percentage of people below the federal poverty threshold. We categorized each of these SES variables into a quartile in which the higher quartiles reflected higher income, less unemployment, more education, or less poverty. We gave all 4 of these SES variables the same weight and totaled them to generate a composite SES score. We compared the lowest quartile of the composite SES score with the remainder of the sample. Investigators in previous studies validated this method for analyzing SES variables.29-32 We measured primary outcome as time in months between diagnosis and death from any cause for OS and as time in months between diagnosis and death specific to the cancer-related diagnosis for DSS. We measured median survival time in length of time in years at which one-half of the patients were still living. We calculated OS and DSS curves by using Kaplan-Meier analysis, and we formally tested differences in survival by using the log-rank test. We used univariate and multivariate Cox proportional hazards regression models with corresponding 95% confidence intervals (CIs) to analyze covariates with regard to OS and DSS. We chose covariates for multivariate analysis by using the variables that were statistically significant in the univariate analysis. We included age at diagnosis, sex, and treatment modality in all multivariate models as a default. Hazard ratio (HR), as defined by the National Cancer Institute, is a measure of how often a particular event occurs in 1 group compared with how often it occurs over time in another group.33 The 95% CI, also as defined by the National Cancer Institute, is defined as an estimated range of values that is likely to include an unknown population parameter.34 We tested and validated these data to meet the assumption of proportional hazards. We established statistical significance at the P < .05 threshold. We performed statistical analysis by using software (SPSS 21, IBM). Investigators in previous studies have validated this statistical method.35-39 RESULTS

The SEER database search generated 232 patients with OMM diagnosed during the period from 1973 through 2012. At the time of diagnosis, 16.8% of these patients were younger than 50 years, 37.5% were aged 50 through 69 years, and 45.7% were 70 years or older (Table 1). For sex, 47.8% of patients were male, and 52.2% were female. For race, 79.3% of patients were white, 5.2% were African American, 8.6% were Asian or Pacific Islander, and 5.2% were Native American, other, or unknown. Normalized racial breakdown according to SEER census data (http://seer.cancer.gov/registries/data.html) yielded 0.33 per 100,000 cases of OMM for whites, 0.12 per 100,000 cases of OMM for African Americans, and 0.17 per 100,000 cases of OMM for Asians or Pacific Islanders. Decade of diagnosis results were that 3.4% of

TABLE 2

Survival data. CHARACTERISTIC

OVERALL SURVIVAL

DISEASE-SPECIFIC SURVIVAL

2.5

4.2

< 50

5.0

5.8

50-69

2.8

4.5

‡ 70

1.9

3.4

1970s

2.5

2.5

1980s

1.7

2.4

1990s

2.5

3.8

2000s

2.7

5.4

Median Overall Survival, y Age at Diagnosis, y

Decade of Diagnosis

Extent of Disease Confined

4.0

7.8

Locally invasive

2.4

4.7

Metastasis

0.8

1.2

4

1.6

2.0

Yes

2.8

4.6

No

1.3

1.9

Lowest quartile

1.8

2.7

All others

2.7

4.7

2

43.0

71.0

5

25.0

40.0

10

15.0

35.0

Tumor Size, Centimeters

Surgery Performed

Composite Socioeconomic Status

Percentage Survival, y

these patients had OMM diagnosed in the 1970s, 12.9%, in the 1980s, 13.4%, in the 1990s, and 70.3%, in the 2000s and beyond. Most of these cases were found in the gingiva (30.6%) or palate (39.2%); 34.9% of patients had localized extent of disease at the time they initially sought care, 33.6% had regional extent, and 16.4% had distant extent. For tumor size, 28.4% of patients had tumors smaller than 2 centimeters at the time they initially sought care, 15.8% had tumors from 2 through 4 cm, and 7.3% had tumors larger than 4 cm. A total of 75.9% of patients had undergone surgery, and 31.5% of patients had undergone radiation therapy. Survival analysis according to Kaplan-Meier curves (Figures 1A and 1B) indicated that 5-year OS and DSS rates for the overall cohort were 25% and 40%, respectively (Table 2). The median OS was 2.5 years, and the median DSS was 4.2 years. Kaplan-Meier univariate analysis results indicated that age at diagnosis had a statistically significant difference in OS (log-rank P ¼ .001) (Figures 2A and 2B, Table 3), with patients

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1.0 < 50 years 50-69 years ≥ 70 years

0.8

CUMULATIVE SURVIVAL

CUMULATIVE SURVIVAL

1.0

0.6

0.4

0.2

0

A

50

100

150

200

250

0.6

0.4

0.2

0

300

B


50

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300

SURVIVAL TIME (MONTHS) 1.0

1.0 1970s 1980s 1990s 2000s

0.8

CUMULATIVE SURVIVAL

CUMULATIVE SURVIVAL

0.8

0

0

0.6

0.4

0.2

1970s 1980s 1990s 2000s

0.8

0.6

0.4

0.2

0

0 0

C

< 50 years 50-69 years ≥ 70 years

50

100

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200

250

0

300


D

50

100

150

200

250

300


Figure 2. A. Kaplan-Meier estimates of overall survival (OS) stratified by age at diagnosis. B. Kaplan-Meier estimates of disease-specific survival (DSS) stratified by age at diagnosis. C. Kaplan-Meier estimates of OS stratified by decade of diagnosis. D. Kaplan-Meier estimates of DSS stratified by decade of diagnosis.

older than 70 years at the time they initially sought care having a poor prognosis (OS, 1.9 years; DSS, 3.4 years). Decade of diagnosis was statistically significant for DSS (log-rank P ¼ .007) (Figures 2C and 2D, Table 3). In addition, further extent of disease correlated with decreased OS (log-rank P < .001) and DSS (log-rank P < .001) (Figures 3A and 3B, Table 3), with distant extent having a dismal prognosis (OS, 0.8 years; DSS, 1.2 years). Larger tumor size correlated with decreased DSS (log-rank P ¼ .001) (Figures 3C and 3D, Table 3),


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and surgical resection correlated with increased survival in both OS (log-rank P < .001) and DSS (log-rank P ¼ .002) (Figures 3E and 3F, Table 3). Table 4 reports multivariate Cox regression analysis of OS and DSS for the overall population, as well as stratified by extent of disease. For the overall cohort, age at diagnosis (HR, 1.74; 95% CI, 1.19 to 2.52; P ¼ .004), decade of diagnosis (HR, 0.55; 95% CI, 0.39 to 0.80; P ¼ .001), extent of disease (HR, 2.51; 95% CI, 1.73 to 3.65; P < .001), and surgical resection (HR, 0.44; 95% CI,


0.20 to 0.99; P ¼ .046) were independent determinants of OS. Decade of diagnosis (HR, 0.43; 95% CI, 0.25 to 0.72; P ¼ .001), extent of disease (HR, 2.69; 95% CI, 1.66 to 4.37; P < .001), tumor size (HR, 2.02; 95% CI, 1.32 to 3.08; P ¼ .001), and surgical resection (HR, 0.24; 95% CI, 0.09 to 0.64; P ¼ .005) were independent predictors of DSS. In the multivariate analysis model stratified according to extent of disease, we combined localized and regional extents into 1 cohort, and we separated distant extent into a different cohort. In the localized- and regionalextent cohort, age at diagnosis (HR, 1.81; 95% CI, 1.16 to 2.83; P ¼ .009), decade of diagnosis (HR, 0.58; 95% CI, 0.39 to 0.86; P ¼ .007), and surgical resection (HR, 0.18; 95% CI, 0.06 to 0.49; P ¼ .001) were independent predictors of OS. Tumor size (HR, 2.09; 95% CI, 1.23 to 3.55; P ¼ .007) and surgical resection (HR, 0.13; 95% CI, 0.03 to 0.53; P ¼ .004) were independent determinants of DSS. For the distant extent cohort, decade of diagnosis (HR, 0.15; 95% CI, 0.04 to 0.59; P ¼ .006) and radiation therapy (HR, 0.18; 95% CI, 0.03 to 0.99; P ¼ .049) were independent predictors for OS, whereas only decade of diagnosis (HR, 0.15; 95% CI, 0.03 to 0.62; P ¼ .009) was an independent predictor for DSS. We identified a correlation between SES and tumor size from our analysis of the SEER data (Figure 4). At the time of diagnosis when initially seeking care, 38.2% of the lowest SES quartile had a tumor smaller than 2 cm; 47.1%, from 2 through 4 cm; and 14.7%, larger than 4 cm. For the rest of the cohort, who had higher SES, 61.6% had a tumor smaller than 2 cm; 24.4%, from 2 through 4 cm; and 14.0%, larger than 4 cm. DISCUSSION

In our study, we found multiple survival and prognostic factors correlated with OMM survival. Increased age, greater extent of disease, and larger tumor size resulted in a decreased survival rate. In contrast, a more recent decade of diagnosis, surgical treatment, and radiation therapy increased survival rate. We also demonstrated that patients of lower SES were associated with decreased OMM survival. OMM is considered to be a rare malignancy. It is highly aggressive, with the potential to metastasize and invade surrounding tissues. The early stages of OMM often manifest asymptomatically, which may contribute to its delayed detection, poor prognosis, and low survival rates. Most of the literature is composed of case reports and single-institution or small multi-institution studies. These studies have limited sample sizes from which it is difficult to draw definitive conclusions about prognostic factors, management, and optimal treatment modalities. Similar to findings from our previous study using the SEER resgistry,40 we have characterized the demographic characteristics, clinicopathologic features, treatment

TABLE 3

Univariate analysis of variables. CHARACTERISTIC

OVERALL SURVIVAL*

DISEASE-SPECIFIC SURVIVAL*

Age

.001

.189

Sex

.873

.663

Decade of Diagnosis

.153

.007

Primary Site

.855

.326

< .001

< .001

Extent

.064

.001

< .001

.002

Radiation Therapy

.165

.422

Composite Socioeconomic Status

.067

.039

Tumor Size Surgery Performed

* Log-rank P value.

outcomes, and socioeconomic factors of patients with OMM. In our study, we categorized patients into overall and confined disease cohorts according to the extent of their disease. An overall disease cohort consisted of people possessing a localized, regional, or distant extent of disease, whereas a confined disease cohort consisted of people possessing only a localized or regional extent of disease. Our study design allowed us to achieve a larger sample size and greater statistical power and enabled us to analyze multiple geographic regions with varying SES. However, such a study design also is accompanied by limitations, including insufficient information on margin status, extent of resection, temporality and method of radiation therapy, tumor recurrence, and patient comorbidities. To our knowledge, this study is the largest analysis of the epidemiologic, outcome, and prognostic factors in patients with OMM. Kaplan-Meier and Cox regression analyses results revealed that increased age was correlated with a lower survival rate for both overall and confined disease cohorts. This correlation matches what investigators have reported in literature, with increased age being a prognostic indicator for survival.9,10,41 Although those affected range in age from 20 through 80 years, OMM develops in most patients older than 40 years and rarely is found in patients younger than 20 years.5,7,10-12 The peak incidence is in the fourth to sixth decades, with 55 years the average patient age at diagnosis.7,9 It is, therefore, critical for clinicians to screen patients early and carefully for any suspicious manifestation of OMM, especially older patients. Our finding of an almost equal OMM sex distribution contrasts with findings from previous reports. However, older, smaller studies exist in which the investigators have shown OMM to have an almost equal sex distribution, with 2 even demonstrating OMM to have a preference for females.16-18 Results from our much larger study indicate a nearly equal sex distribution of OMM.

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1.0 Confined Locally invasive Metastatic

0.8

0.6

0.4

0.2

CUMULATIVE SURVIVAL

CUMULATIVE SURVIVAL

1.0

0.8

0.6

0.4

0.2

0

0 0

A

50

100

150

200

250

0

300

B


50

100

150

0.8

0.6

0.4

0.2

CUMULATIVE SURVIVAL

< 2 cm 2-4 cm > 4 cm

0

C

50

100

150

200

250

300


< 2 cm 2-4 cm > 4 cm

0.8

0.6

0.4

0.2

0

300

D


50

100

150

200

250

300

SURVIVAL TIME (MONTHS) 1.0

1.0

No surgery Surgery performed

No surgery Surgery performed 0.8

CUMULATIVE SURVIVAL

CUMULATIVE SURVIVAL

250

0

0

0.6

0.4

0.2

0.8

0.6

0.4

0.2

0

0 0

E

200

1.0

1.0

CUMULATIVE SURVIVAL

Confined Locally invasive Metastatic

50

100

150

200

250


0

300

F

50

100

150

200

250

300


Figure 3. A. Kaplan-Meier estimates of overall survival (OS) stratified by extent of disease. B. Kaplan-Meier estimates of disease-specific survival (DSS) stratified by extent of disease. C. Kaplan-Meier estimates of OS stratified by tumor size. D. Kaplan-Meier estimates of DSS stratified by tumor size. E. Kaplan-Meier estimates of OS stratified by surgery. F. Kaplan-Meier estimates of DSS stratified by surgery. cm: Centimeters.


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TABLE 4 Although OMM carries a dismal prognosis, a more recent decade of Cox proportional hazards model for multivariate diagnosis is associated with statistically analysis for the overall, confined, and distant significant improvement in survival in metastasis populations. both univariate and multivariate analyses for the overall, confined, and CHARACTERISTIC OVERALL SURVIVAL DISEASE-SPECIFIC SURVIVAL metastatic disease groups. This trend is Hazard Ratio (95% P Hazard Ratio (95% P demonstrated in literature through inConfidence Interval) Value Confidence Interval) Value dividual studies reported from the 1950s Overall to the 2000s, in which the 5-year surAge 1.74 (1.19 to 2.52) .004 1.29 (0.80 to 2.06) .294 vival rate gradually increases as the Sex 0.92 (0.56 to 1.50) .738 1.26 (0.65 to 2.44) .498 decade becomes more recent.8,11,15,16,42-45 Decade of diagnosis 0.55 (0.39 to 0.80) .001 0.43 (0.25 to 0.72) .001 The development of new therapies, adExtent 2.51 (1.73 to 3.65) < .001 2.69 (1.66 to 4.37) < .001 vances in surgical interventions, and the Tumor size 1.34 (0.96 to 1.87) .085 2.02 (1.32 to 3.08) .001 addition of individualized adjuvant Surgery 0.44 (0.20 to 0.99) .046 0.24 (0.09 to 0.64) .005 treatment decisions may have contribRadiation therapy 0.72 (0.43 to 1.19) .196 0.57 (0.29 to 1.11) .099 uted to improving the 5-year survival Composite 0.82 (0.48 to 1.39) .453 0.58 (0.29 to 1.19) .138 rates over those of the previous several socioeconomic status decades. Confined and Locally Invasive Disease In terms of prognosis, the extent of 1.81 (1.16 to 2.83) .009 1.44 (0.81 to 2.59) .218 disease at the time the patient seeks care Age Sex 0.98 (0.56 to 1.72) .934 1.32 (0.61 to 2.83) .483 may be the most important factor in 0.58 (0.39 to 0.86) .007 0.55 (0.30 to 1.01) .054 determining survival.11 In our study, we Decade of diagnosis Tumor size 1.37 (0.89 to 2.10) .154 2.09 (1.23 to 3.55) .007 found extent of disease to be an indeSurgery 0.18 (0.06 to 0.49) .001 0.13 (0.03 to 0.53) .004 pendent prognostic risk factor of both Radiation therapy 1.13 (0.64 to 1.97) .680 0.86 (0.40 to 1.87) .708 OS and DSS, which is shown in the Composite 0.64 (0.34 to 1.20) .161 0.61 (0.25 to 1.46) .265 Kaplan-Meier and Cox regression anasocioeconomic status lyses for the overall disease group. The Metastatic Disease degree of extent of disease correlated Age 2.63 (0.88 to 7.84) .083 2.17 (0.63 to 7.48) .220 with decreased survival, with distant Sex 2.78 (0.62 to 12.45) .182 2.51 (0.31 to 20.30) .389 extent having a poorer prognosis (OS, Decade of diagnosis 0.15 (0.04 to 0.59) .006 0.15 (0.03 to 0.62) .009 0.8 years; DSS, 1.2 years). This finding is Tumor size 1.08 (0.51 to 2.28) .846 2.83 (0.77 to 10.43) .117 in agreement with those of Singh and Surgery 0.72 (0.16 to 3.35) .675 0.52 (0.07 to 3.72) .518 23 colleagues in which 3 patients with 0.18 (0.03 to 0.99) .049 0.81 (0.07 to 9.91) .866 OMM who sought care at an advanced Radiation therapy 2.19 (0.37 to 13.01) .391 0.27 (0.02 to 4.80) .373 stage all died within 1 year of diagnosis. Composite socioeconomic status In another study, Kumar and colleagues7 found that the extent of the disease is related to the prognosis of the disease. There- tumors smaller than 2 cm had significantly prolonged fore, it is again critical for clinicians to incorporate early survival time compared with those with tumors larger screenings for OMM in their patient examinations. than 2 cm. Hashemi Pour14 reported that most OMMs are larger than 4 millimeters at the time the patient Clinical lesions with asymmetry, change in color, swelling within a pigmented area, or hemorrhage should initially seeks care, which may contribute to the poorer be examined with suspicion. Preventing distant metassurvival rates seen in OMM compared with those seen in cutaneous melanomas. tasis is necessary in improving the survival of patients with OMM.8 Surgical resection with negative margins is the An additional prognostic factor related to OMM mainstay of treatment for OMM.14 Through Kaplansurvival was tumor size, as investigators reported previ- Meier and Cox regression analyses, we found that surously.7,41 Larger tumor size is correlated with poorer gical treatment improves survival in both overall and survival in Kaplan-Meier and Cox regression analyses for confined disease cohorts, which matches what inthe overall and confined disease cohorts. Tumors larger vestigators have reported previously.5,7 Kumar and colleagues7 reported similar findings of patients treated than 4 cm decreased OS and DSS to 1.6 and 2.0 years, respectively, whereas tumors smaller than 2 cm had with surgery exhibiting better survival rates of 10 to higher OS and DSS of 3.3 and 11.1 years, respectively. This 26 months, whereas patients treated with chemotherapy had a survival range of 5 to 9 months. However, local trend is in congruence with findings in the literature. Zhu and colleagues41 demonstrated that patients with control does not necessarily predict survival.11,46 Many

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diagnosis and consequently poor prognosis. Early screening is critical Lowest quartile for OMM survival, espe60 All others cially for older patients and patients of lower 50 SES. Patients of lower SES may have less access 40 to regular care and decreased frequency of 30 routine examinations, which may decrease their 20 survival. Dentists need to incorporate screenings 10 for OMM into their practices because early 0 and careful detection is 2-4 cm > 4 cm < 2 cm essential for OMM survival. We advise cliniTUMOR SIZE cians to refer to the evidence-based clinical Figure 4. Socioeconomic status correlation with tumor size. cm: Centimeters. recommendations for oral cancer screenings patients with radical excision of tumors develop a developed by the American Dental Association Council recurrence,11,47 which may be due to anatomic comon Scientific Affairs Expert Panel on Screening for plexities that make complete excision of OMM in the Oral Squamous Cell Carcinomas.51 Routine dental 9,46 Moreover, the proximity of bone screenings for general oral mucosal diseases and oral oral cavity difficult. and muscles and the rich vascularity of the oral cavity mucosal malignancies are important, and including may facilitate metastasis of OMM more readily than do OMM screenings in routine examinations may be cutaneous melanomas.4,9,48 beneficial in improving its prognosis. n Although surgical resection is effective in treating Dr. Robert J. Lee is an orthodontics resident, Department of Orthodontics, confined OMM, adjuvant treatment such as radiation School of Dentistry, University of California San Francisco, San Francisco, CA. 8,49 therapy has been receiving increased attention. Results Dr. Serena A. Lee is a dental student, School of Dentistry, University of from previous studies show that patients occasionally have California Los Angeles, Los Angeles, CA. Dr. Lin is a research associate, School of Dentistry, University of demonstrated favorable responses to radiation therapy California Los Angeles, Los Angeles, CA. despite the classically radio-insensitive nature of melaDr. Kevin K. Lee is a dental student, School of Dentistry, University of noma.14 The results of our Cox regression analysis for the California Los Angeles, Los Angeles, CA. Dr. Christensen is an associate professor and the chair, Department of metastatic disease group agrees with findings in the literOral & Maxillofacial Pathology, School of Dentistry, University of California ature, demonstrating that radiation therapy is associated Los Angeles, 10833 Le Conte Ave., CHS 53-058, Los Angeles, CA 90095, with improved survival for metastatic OMM. e-mail [email protected]. Address correspondence to Dr. In our study, we also report a correlation between SES Christensen. and tumor size, a finding consistent with those in previous Disclosure. None of the authors reported any disclosures. studies of cutaneous melanoma.50 Kaplan-Meier analysis Drs. R.J. Lee and S.A. Lee equally contributed as co-first authors. results showed that a lower composite SES was associated with decreased survival. Although the lowest quartile had a 1. Munde A, Juvekar MV, Karle RR, Wankhede P. Malignant melanoma lower percentage of tumors smaller than 2 cm (38.2%), they had a higher percentage of tumors 2 to 4 cm (47.1%) of the oral cavity: report of two cases. Contemp Clin Dent. 2014;5(2): 227-230. compared with those in the higher SES quartiles (61.6% 2. Padhye A, D’souza J. Oral malignant melanoma: a silent killer? for < 2 cm and 24.4% for 2 through 4 cm). People in the J Indian Soc Periodontol. 2011;15(4):425-428. 3. Lamichhane NS, An J, Liu Q, Zhang W. Primary malignant mucosal lowest quartile of SES most likely had their tumors diagof the upper lip: a case report and review of the literature. BMC nosed at a later time because of less access to regular care melanoma Res Notes. 2015;8(1):499. than patients of higher SES have. 4. Hasan S, Jamdar SF, Jangra J, Al Beaiji SM. Oral malignant melanoma: POPULATION (%)

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OMM is a rare malignancy that generally manifests asymptomatically in the early stages, resulting in late


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