Abstract
Background
Prior studies documented poorer outcomes in patients with cutaneous head and neck melanoma (CHNM) relative to those with melanoma at other sites. We evaluated survival differences attributable to tumor location in patients with CHNM.
Methods
We queried the Surveillance, Epidemiology, and End Results (SEER) database for patients undergoing surgery for CHNM from 1988 to 2006, excluding patients without biopsy-proven diagnoses, those diagnosed at autopsy, and patients with distant metastases. Using the Kaplan-Meier method, we assessed patient, tumor, and treatment-specific factors on overall survival (OS) and melanoma specific survival (MSS). Cox proportional hazards models assessed the role of tumor location (ear, eyelid, face, lip, scalp/neck) on OS and MSS while controlling for patient age, sex, race, tumor thickness, tumor ulceration, lymph node status, histologic subtype, type of surgery, and use of radiation. Risks of overall and melanoma-specific mortality were reported as hazard ratios (HR) with 95% confidence intervals (CI).
Results
Among 27,097 patients, 10-year rates of OS and MSS were 56.1% and 84.7%, respectively. On multivariate analysis, scalp/neck primary site was associated with an increased risk of overall (HR 1.20, CI 1.14-1.26; p<0.001) and melanoma-specific mortality (HR 1.64, CI 1.49-1.80, p<0.001) relative to melanomas of the face. Tumors of the lip had poorer MSS (HR 1.55; CI 1.05-2.28, P= 0.03) but not OS (HR 1.03, CI 0.80-1.34; p=0.80).
Conclusions
Patients with melanomas of the scalp/ neck have poorer OS and MSS and those with lip melanomas have poorer MSS. These anatomic areas should not be overlooked when performing skin examinations.
Keywords: head and neck neoplasms, melanoma, tumor location, population analysis, survival
Introduction
Cutaneous head and neck melanomas (CHNM) constitute 12-21% of melanomas diagnosed annually(1-5). CHNM have poorer outcomes relative to melanomas of other sites (MOS)(2-3, 6). CHNM may be thicker at the time of diagnosis relative to MOS and present at a more advanced stage(2, 5). Anatomic constraints of the head and neck region may make optimal resection margins difficult or impossible to achieve(5, 7-11). Furthermore, the lymphatic drainage of the head and neck is variable and complex(12-16). Each of these factors are hypothesized to account for the relatively poor prognosis attributed to CHNM. It is unclear if CHNM represents an entity separate from MOS(9, 17).
While prior studies have evaluated the survival differences between CHNM and MOS(2-3, 9, 18), few have assessed survival differences attributable to tumor location among patients with CHNM. Our objective was to use a large, population-based database to evaluate tumor location as a prognostic factor in patients with CHNM.
Materials and Methods
We used the Surveillance Epidemiology and End Results (SEER) database of the National Cancer Institute to identify all patients with CHNM diagnosed from 1988 to 2006. Characteristics of the SEER database, including the registries represented and the data fields included, have been reported by our group previously(19-22). All cases of primary, histologically confirmed, CHNM were eligible. Those with metastatic disease or mucosal melanoma were excluded. Patients identified by death certificate or autopsy, and those with missing cause of death were also excluded.
Using rules developed by SEER, we calculated survival time as the number of completed months between the date of diagnosis and whichever occurred first: date of death, date last known to be alive, or December 31, 2006. The endpoints for the present study were OS and MSS. For calculations of OS and MSS, patients who were lost to follow-up or survived beyond December 31, 2006 were coded as censored observations. Similarly, for calculations of MSS, patients who died from non-melanoma related causes were coded as censored observations.
We performed univariate analyses of patient, tumor, and treatment-specific factors on OS and MSS using the Kaplan-Meier method. The log rank test assessed differences among survival curves. Variables assessed included tumor location (ear, eyelid, face, lip, scalp/neck), patient age, sex, race/ethnicity (white, Asian, black, and Hispanic), histologic subtype (melanoma not otherwise specified [NOS], superficial spreading, lentigo maligna, nodular, desmoplastic, and other [includes acral, amelanotic, balloon cell, epithelioid, and spindle cell]), tumor depth (Clark level and Breslow depth), presence of tumor ulceration (present, absent, unknown), lymph node status (positive, negative, unknown/not assessed), type of surgery (wide local excision, local excision, and Mohs excision), and use of radiation (yes, no, unknown). Clinicopathological characteristics of those patients with tumors of the scalp/neck were compared to patients with tumors of other head and neck locations using Chi square.
Cox proportional hazards models were constructed utilizing all covariates from the univariate analysis, regardless of significance. For each variable, we included missing or unknown data as a separate category in the analysis.
Risks of overall and melanoma-specific mortality were reported as hazard ratios (HR) with 95% confidence intervals (CI); significance was set at p ≤ 0.05. All statistical analyses were two-tailed and performed using STATA version 11 (StataCorp, College Station, Texas) and SPSS version 18.0.0 (SPSS, Chicago, Illinois).
Results
Patient, tumor, and treatment characteristics are presented in Table 1. Briefly, the majority of patients were older (mean age = 65 years) white (94.3%) men (69.8%). Tumors were most commonly noted on the face (48.1%) and scalp/neck (34.3%), with less than 20% arising from the ear, eyelid, or lip. The majority of melanomas (57.4%) were < 1 mm thick, with 6% > 4 mm thick. Lymph nodes were not evaluated or their status was unknown in 70.2% of patients. Of patients with known lymph node status (n=8075), 94.6% were node-negative. The three most prevalent histologic subtypes were Melanoma NOS (42.6%), superficial spreading (23.4%), and lentigo maligna (19.9%); nodular melanomas constituted 8.2% of cases.
Table 1.
Clinicopathological characteristics of 27,097 patients with cutaneous head and neck melanoma.
| Variable | Mean or Percent |
|---|---|
| Age | 65 |
|
| |
| Male | 69.8 |
|
| |
| Race/Ethnicity | |
| White | 94.3 |
| Hispanic | 2.5 |
| Black | 0.2 |
| Asian | 0.4 |
| Other | 2.6 |
|
| |
| Tumor Location | |
| Face | 48.1 |
| Scalp/Neck | 34.3 |
| Ear | 15.1 |
| Eyelid | 1.7 |
| Lip | 0.8 |
|
| |
| Histologic Subtype | |
| Melanoma NOS | 42.6 |
| Superficial Spreading | 23.4 |
| Lentigo Maligna | 19.9 |
| Nodular | 8.2 |
| Desmoplastic | 2.8 |
| Other | 3.2 |
|
| |
| Breslow Thickness | |
| <1 mm | 57.4 |
| 1-2 mm | 15.6 |
| 2-4 mm | 10.0 |
| >4 mm | 6.0 |
| Unknown | 11.0 |
|
| |
| Clark Level | |
| I/II | 35.7 |
| III | 18.1 |
| IV | 24.1 |
| V | 6.1 |
| Unknown | 16.0 |
|
| |
| N Stage | |
| N0 | 28.2 |
| N1 | 0.8 |
| N2 | 0.6 |
| N3 | 0.2 |
| Unknown/ Not examined | 70.2 |
|
| |
| Tumor Ulceration | |
| Yes | 7.9 |
| No | 24.9 |
| Unknown | 67.1 |
|
| |
| Radiation | |
| Yes | 2.1 |
| No | 97.9 |
Univariate analysis revealed increasing age, gender, histologic subtype, Breslow depth, Clark's level, tumor ulceration, lymph node status, and radiation therapy as predictors of OS and MSS (all p<0.001). Additionally, tumor location and surgery type predicted MSS (both p<0.001).
Kaplan-Meier survival curves depicting OS and MSS dependent on location of tumor are shown in Figure 1 and Figure 2, respectively. Ten-year OS was 55.1% and ten-year MSS was 84.7% for all patients with CHNM. For tumors of the scalp/neck, 10-year rates of OS and MSS were 57.2% and 78.3%, respectively. 10-year OS and MSS for CHNM at sites other than the scalp/neck were 55.6% and 88.0%, respectively. Patient and tumor characteristics of those with melanomas of the scalp/neck relative to CHNM at other sites locations are presented in Table 2.
Figure 1.
Univariate Kaplan-Meier survival curves of overall survival according to primary melanoma site.
Figure 2.
Univariate Kaplan-Meier survival curves of melanoma-specific survival according to primary melanoma site.
Table 2.
Clinicopathological characteristics of patients with scalp/ neck melanomas vs. melanomas at other head and neck sites.
| Scalp/ Neck | Other Head and Neck Sites |
||
|---|---|---|---|
| Variable | P value | ||
| % or mean | |||
| Age | 61 | 66 | P<0.001 |
|
| |||
| Female | 25.8 | 32.5 | P<0.001 |
|
| |||
| Ethnicity | P<0.001 | ||
| White | 94.9 | 93.9 | |
| Asian | 0.4 | 0.4 | |
| Black | 0.3 | 0.2 | |
| Hispanic | 1.9 | 2.8 | |
|
| |||
| Histologic Subtype | P<0.001 | ||
| Melanoma NOS | 44.2 | 41.7 | |
| Superficial Spreading | 28.3 | 20.8 | |
| Lentigo Maligna | 11.7 | 24.2 | |
| Nodular | 9.6 | 7.5 | |
| Desmoplastic | 3.1 | 2.7 | |
|
| |||
| Breslow Thickness | P<0.001 | ||
| <1 mm | 54.4 | 59.0 | |
| 1-2 mm | 15.9 | 15.4 | |
| 2-4 mm | 11.1 | 9.4 | |
| >4 mm | 8.8 | 4.6 | |
| Unknown | 9.8 | 11.6 | |
|
| |||
| Clark's Level | P<0.001 | ||
| I/II | 31.8 | 37.8 | |
| III | 18.9 | 17.7 | |
| IV | 25.7 | 23.3 | |
| V | 8.3 | 4.9 | |
| Unknown | 15.3 | 16.3 | |
|
| |||
| Tumor Ulceration | 9.8 | 7.0 | P<0.001 |
|
| |||
| N stage | P<0.001 | ||
| N0 | 28.6 | 28.0 | |
| N1 | 1.3 | 0.5 | |
| N2 | 1.0 | 0.4 | |
| N3 | 0.5 | 0.1 | |
| Unknown/ Not examined | 68.7 | 71.0 | |
|
| |||
| Surgery Type | P<0.001 | ||
| Local | 52.3 | 57.9 | |
| Wide | 45.7 | 39.1 | |
| Mohs | 1.2 | 2.3 | |
|
| |||
| Radiation Therapy | 2.7 | 1.8 | P<0.001 |
Multivariate analysis (Table 3) revealed tumors of the scalp and neck to be associated with poorer OS (HR 1.20, 95% CI 1.14-1.26; p<0.001). Other factors associated with poorer OS included increasing age (HR 1.06, 95% CI 1.06-1.06; p<0.001), nodular histology (HR 1.14, 95% CI 1.06-1.23; p=0.001), increasing Breslow thickness (HR 1.29-1.95, 95% CI 1.20-2.15; p<0.001), increasing Clark's level (HR 1.20-1.76, 95% CI 1.11-1.97; p<0.001), nodal involvement (HR 1.92-3.98, 95% CI 1.36-5.95; p<0.001), tumor ulceration (HR 1.50, 95% CI 1.28-1.77; p<0.001), and administration of radiation therapy (HR 1.54, 95% CI 1.35-1.76; p<0.001). Factors associated with improved OS included female gender (HR 0.76, 95% CI 0.72-0.80; p<0.001), wide excision surgery (HR 0.83, 95% CI 0.78-0.87; p<0.001), and lentigo maligna (HR 0.90, 95% CI 0.85-0.96; p<0.01) and desmoplastic (HR 0.78, 95% CI 0.68-0.89; p<0.001) histologies.
Table 3.
Multivariate analysis model incorporating multiple patient and tumor-related characteristics for overall survival.
| Overall Survival |
|||
|---|---|---|---|
| Variable | HR | 95% CI | P value |
| Age | *1.06 | 1.06-1.06 | <0.001 |
|
| |||
| Female | *0.76 | 0.72-0.80 | <0.001 |
|
| |||
| Ethnicity | |||
| White | Ref | ||
| Asian | 0.78 | 0.52-1.19 | 0.25 |
| Black | 1.19 | 0.73-1.95 | 0.48 |
| Hispanic | 1.14 | 0.97-2.88 | 0.09 |
|
| |||
| Histologic Subtype | |||
| Melanoma NOS | Ref | ||
| Superficial Spreading | 0.96 | 0.90-1.02 | 0.16 |
| Lentigo Maligna | *0.90 | 0.85-0.96 | 0.002 |
| Nodular | *1.14 | 1.06-1.23 | 0.001 |
| Desmoplastic | *0.78 | 0.68-0.89 | <0.001 |
|
| |||
| Tumor Location | |||
| Face | Ref | ||
| Ear | 0.94 | 0.87-1.00 | 0.06 |
| Eyelid | 0.92 | 0.77-1.10 | 0.37 |
| Lip | 1.03 | 0.80-1.34 | 0.80 |
| Scalp/neck | *1.20 | 1.14-1.26 | <0.001 |
|
| |||
| Breslow depth | |||
| <1mm | Ref | ||
| 1-2mm in depth | *1.29 | 1.20-1.39 | <0.001 |
| 2-4mm in depth | *1.62 | 1.50-1.76 | <0.001 |
| >4mm in depth | *1.95 | 1.77-2.15 | <0.001 |
| Unknown depth | *1.11 | 1.03-1.20 | <0.001 |
|
| |||
| Clark level | |||
| I/II | Ref | ||
| III | *1.20 | 1.11-1.29 | <0.001 |
| IV | *1.38 | 1.28-1.49 | <0.001 |
| V | *1.78 | 1.60-1.97 | <0.001 |
| Unknown | *1.40 | 1.30-1.52 | <0.001 |
|
| |||
| N stage | |||
| N0 | Ref | ||
| N1 | *2.64 | 1.90-3.66 | <0.001 |
| N2 | *1.92 | 1.36-2.70 | <0.001 |
| N3 | *3.98 | 2.67-5.95 | <0.001 |
| Unknown/ Not examined | *1.20 | 1.03-1.39 | 0.02 |
|
| |||
| Surgery Type | |||
| Local | Ref | ||
| Wide | *0.83 | 0.78-0.87 | <0.001 |
| Mohs | 0.86 | 0.65-1.16 | 0.33 |
|
| |||
| Tumor ulceration | |||
| No | Ref | ||
| Yes | *1.50 | 1.28-1.77 | <0.001 |
| Unknown | 1.14 | 0.97-1.35 | 0.12 |
|
| |||
| Radiation | |||
| No | Ref | ||
| Yes | *1.54 | 1.35-1.76 | <0.001 |
Designates statistical significance at p≤0.05
Multivariate analysis of MSS is presented in Table 4. Tumors of the scalp/ neck were associated with decreased MSS (HR 1.64, 95% CI 1.49-1.80; p<0.001), as were tumors of the lip (HR 1.55, 95% CI 1.05-2.28; p=0.03). Other factors associated with poorer MSS included increasing age (HR 1.02, 95% CI 1.01-1.02; p<0.001), nodular histology (HR 1.26, 95% CI 1.12-1.41; p<0.001), increasing Breslow thickness (HR 1.75-2.90, 95% CI 1.53-3.41; p<0.001), increasing Clark's level (HR 2.63-6.04, 95% CI 2.17-7.46; p<0.001), nodal involvement (HR 2.05-3.09, 95% CI 1.34-4.82; p<0.001), tumor ulceration (HR 1.92, 95% CI 1.48-2.50; p<0.001), and administration of radiation therapy (HR 2.41, 95% CI 2.05-2.83; p<0.001). Factors associated with improved MSS included female gender (HR 0.70, 95% CI 0.63-0.77; p<0.001), wide excision surgery (HR 0.97, 95% CI 0.80-0.95; p<0.01), and lentigo maligna (HR 0.55, 95% CI 0.46-0.64; p<0.001), and desmoplastic (HR 0.65, 95% CI 0.53-0.80; p<0.001) histologies.
Table 4.
Multivariate analysis model incorporating multiple patient and tumor-related characteristics for melanoma-specific survival.
| Melanoma- Specific Survival |
|||
|---|---|---|---|
| Variable | HR | 95% CI | P value |
| Age | *1.01 | 1.01-1.02 | <0.001 |
|
| |||
| Female | *0.70 | 0.63-0.77 | <0.001 |
|
| |||
| Ethnicity | |||
| White | Ref | ||
| Asian | 1.05 | 0.55-2.03 | 0.88 |
| Black | 1.36 | 0.70-2.64 | 0.37 |
| Hispanic | 1.19 | 0.92-1.54 | 0.20 |
|
| |||
| Histologic Subtype | |||
| Melanoma NOS | Ref | ||
| Superficial Spreading | 1.03 | 0.92-1.15 | 0.65 |
| Lentigo Maligna | *0.55 | 0.46-0.64 | <0.001 |
| Nodular | *1.26 | 1.12-1.41 | <0.001 |
| Desmoplastic | *0.65 | 0.53-0.80 | <0.001 |
|
| |||
| Tumor Location | |||
| Face | Ref | ||
| Ear | 0.92 | 0.81-1.06 | 0.25 |
| Eyelid | 1.02 | 0.71-1.47 | 0.91 |
| Lip | *1.55 | 1.05-2.28 | 0.03 |
| Scalp/neck | *1.64 | 1.49-1.80 | <0.001 |
|
| |||
| Breslow depth | |||
| <1mm | Ref | ||
| 1-2mm in depth | *1.75 | 1.53-2.00 | <0.001 |
| 2-4mm in depth | *2.69 | 2.34-3.10 | <0.001 |
| >4mm in depth | *2.90 | 2.46-3.41 | <0.001 |
| Unknown depth | *1.43 | 1.22-1.68 | <0.001 |
|
| |||
| Clark level | |||
| I/II | Ref | ||
| III | *2.63 | 2.17-3.18 | <0.001 |
| IV | *3.78 | 3.14-4.55 | <0.001 |
| V | *6.04 | 4.90-7.46 | <0.001 |
| Unknown | *3.96 | 3.28-4.79 | <0.001 |
|
| |||
| N stage | |||
| N0 | Ref | ||
| N1 | *3.09 | 2.10-4.56 | <0.001 |
| N2 | *2.05 | 1.34-3.13 | 0.001 |
| N3 | *2.97 | 1.83-4.82 | <0.001 |
| Unknown/ Not examined | *1.30 | 1.02-1.65 | 0.03 |
|
| |||
| Surgery Type | |||
| Local | Ref | ||
| Wide | *0.87 | 0.80-0.95 | 0.02 |
| Mohs | 1.21 | 0.72-2.03 | 0.47 |
|
| |||
| Tumor ulceration | |||
| No | Ref | ||
| Yes | *1.92 | 1.48-2.50 | <0.001 |
| Unknown | 1.24 | 0.94-1.64 | 0.12 |
|
| |||
| Radiation | |||
| No | Ref | ||
| Yes | *2.41 | 2.05-2.83 | <0.001 |
Designates statistical significance at p≤0.01
Discussion
CHNM has a poorer prognosis relative to MOS(2-3, 9, 18). Data regarding the prognostic importance of tumor location in CHNM are limited. Utilizing population-based data, we have reported on the largest series of CHNM patients to date.
We identified scalp/neck melanomas as having a greater risk of melanoma-specific mortality as well as death due to any cause. Although upon univariate Kaplan-Meier survival analysis in which tumor location did not appear to offer prognostic significance, after adjusting for important tumor and patient related characteristics, patients with scalp/neck melanoma demonstrated a 20% increased risk of death due to any cause and a 64% increased risk of melanoma-related death relative to patients with facial melanomas. These findings confirm the findings reported by Leong and the Sentinel Lymph Node Working Group(23). They reported a series of 614 patients with CHNM who underwent sentinel node biopsy and found that those with scalp melanomas had more than a 3-fold increased risk of death relative to melanomas of the face. In our study, lymph node status was unknown for approximately 70% of patients. It is possible that those in the scalp/neck melanoma group had higher rates of lymph node metastasis than those with CHNM at other sites, but information regarding these metastases was missing or not obtained. The high rate of patients with unknown lymph node status is likely due to our data incorporating a decade (1988-1998) where rates of lymphatic mapping and sentinel node biopsy for CHNM nodal staging was quite low. In the absence of sentinel node biopsy to facilitate nodal staging, use of elective lymph node dissection for CHNM can be fraught with difficulty due to the variable and complex lymphatic drainage of the head and neck. We surmise that many patients with CHNM did not have lymph node staging performed prior to the era of sentinel node biopsy. Even among those patients that did undergo lymphatic mapping and sentinel node biopsy, higher false negative rates for sentinel lymph node biopsies of the neck are well-documented(14-15, 24-31). Up to 30% of patients with lymph node metastases from neck melanomas bypass the nearest node and involve nodes at more distant sites(32). Additionally, we found that patients with CHNM involving the lip had a 55% increase in the risk of melanoma-related death relative to melanomas of the face, which is previously un-reported.
Along with suggesting that tumor location influences survival in CHNM, our data validate known prognostic factors for melanoma such as increasing age, male gender, histologic subtype, Breslow depth, Clark's level, tumor ulceration, and nodal status(9, 33-35).
Lachiewicz et al. have previously used SEER data to evaluate CHNM patients, but restricted their study to survival differences between patients with scalp/neck melanomas and those with melanomas of all sites(3). Their study also used the smaller SEER-13 registry, which excludes Arizona Indian, greater California, Kentucky, and New Jersey cancer registries. Furthermore, Lachiewicz et al. excluded all non-white (including Hispanic) patients, and only included cases from 1992-2003. They found that patients with melanoma of the scalp/neck had an 84% greater chance of melanoma-related death as compared to those with melanomas of the extremity (HR 1.84, 95% CI 1.62-2.10). Unlike the current study, their endpoints did not include OS. Our study utilized the SEER-17 database, which captures an estimated 26% of cancers diagnosed annually in the United States. Unlike data from single and multi-institution studies that can be saddled with referral and reporting biases, our population-based data reflect the care of CHNM across a spectrum of community hospitals, health maintenance organizations, county hospitals, and academic medical centers, and may therefore be more generalizeable.
Moreover, to our knowledge, ours is the first study to examine the importance of tumor location within the head and neck melanoma population. We have confirmed that tumors of the scalp/ neck are associated with poorer MSS as previously reported but have also shown a significant effect on OS as well. Likewise we have demonstrated that melanomas of the lip are associated with poorer MSS as compared to melanomas of the face.
Limitations of SEER data have been reported previously(36). Briefly, SEER does not provide information regarding patient co-morbidities, adequacy of surgery (including margin status), use of systemic adjuvant or neoadjuvant therapy, socioeconomic status, or insurance status. Even among data fields included within SEER, data may be missing or incomplete. In our study, missing or incomplete data were analyzed as a separate category so that we could estimate the effects of this missing data on survival outcomes. In our study, increased risk of death due to any cause was predicted by unknown Breslow depth (11% increased risk), unknown Clark level (40% increased risk), and unknown nodal status (20% increased risk). Similarly, melanoma-specific mortality was predicted by unknown Breslow depth (43% increased risk), unknown Clark level (nearly 4-fold increase risk), and unknown nodal status (30% increased risk).
SEER groups tumors of the scalp and neck together—thus it is not possible to analyze melanomas of the scalp independently. Table 2 presents the differences between melanomas of the scalp/ neck and melanomas of other head and neck sites. There are significant differences in respect to Breslow thickness, tumor ulceration, and N stage. Importantly, however, tumor location remained an important predictor of survival upon multivariate analysis with inclusion of these other tumor and patient variables (Table 3). Data from other studies have suggested that tumors in these areas may have clinically different behavior(9, 33, 37). It is possible that melanomas of the scalp present at an advanced stage as compared to melanomas of other locations within the head and neck. Future studies are needed to evaluate differences between melanomas of the scalp and melanomas of the neck.
Routine skin screening is an integral component of early melanoma detection. Early detection of disease, when followed closely thereafter by adequate surgical resection, increases the likelihood of cure(38). In this regard, our data have several public health implications. Distinct from melanomas of other sites, wound closure is often challenging in patients with CHNM undergoing wide local excision. If these melanomas could be diagnosed earlier, thinner depth of invasion could allow for narrower margins and the need for sentinel node biopsy may be obviated. Patients and primary health care providers should be educated that routine evaluation of the head and neck, and especially of the lips, scalp and neck, should be performed as part of the standard skin examination.
Acknowledgments
Supported by Grant Number UL1 RR024146 from the National Center for Research Resources (NCRR) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NNCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Presented in part at the 5th Annual Academic Surgical Congress, February 3-5, 2010, San Antonio, Texas.
Disclosures: none
References
- 1.Golger A, Young DS, Ghazarian D, Neligan PC. Epidemiological features and prognostic factors of cutaneous head and neck melanoma: a population-based study. Arch Otolaryngol Head Neck Surg. 2007;133(5):442–7. doi: 10.1001/archotol.133.5.442. [DOI] [PubMed] [Google Scholar]
- 2.Gillgren P, Mansson-Brahme E, Frisell J, Johansson H, Larsson O, Ringborg U. A prospective population-based study of cutaneous malignant melanoma of the head and neck. Laryngoscope. 2000;110(9):1498–504. doi: 10.1097/00005537-200009000-00017. [DOI] [PubMed] [Google Scholar]
- 3.Lachiewicz AM, Berwick M, Wiggins CL, Thomas NE. Survival differences between patients with scalp or neck melanoma and those with melanoma of other sites in the Surveillance, Epidemiology, and End Results (SEER) program. Arch Dermatol. 2008;144(4):515–21. doi: 10.1001/archderm.144.4.515. [DOI] [PubMed] [Google Scholar]
- 4.Cox NH, Aitchison TC, Sirel JM, MacKie RM. Comparison between lentigo maligna melanoma and other histogenetic types of malignant melanoma of the head and neck. Scottish Melanoma Group. Br J Cancer. 1996;73(7):940–4. doi: 10.1038/bjc.1996.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Hoersch B, Leiter U, Garbe C. Is head and neck melanoma a distinct entity? A clinical registry-based comparative study in 5702 patients with melanoma. Br J Dermatol. 2006;155(4):771–7. doi: 10.1111/j.1365-2133.2006.07455.x. [DOI] [PubMed] [Google Scholar]
- 6.Balch CM, Soong SJ, Milton GW, et al. A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia. Ann Surg. 1982;196(6):677–84. doi: 10.1097/00000658-198212001-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Sullivan SR, Scott JR, Cole JK, et al. Head and neck malignant melanoma: margin status and immediate reconstruction. Ann Plast Surg. 2009;62(2):144–8. doi: 10.1097/SAP.0b013e31817dadc8. [DOI] [PubMed] [Google Scholar]
- 8.Stadelmann WK, McMasters K, Digenis AG, Reintgen DS. Cutaneous melanoma of the head and neck: advances in evaluation and treatment. Plast Reconstr Surg. 2000;105(6):2105–26. doi: 10.1097/00006534-200005000-00031. [DOI] [PubMed] [Google Scholar]
- 9.Urist MM, Balch CM, Soong SJ, et al. Head and neck melanoma in 534 clinical Stage I patients. A prognostic factors analysis and results of surgical treatment. Ann Surg. 1984;200(6):769–75. doi: 10.1097/00000658-198412000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Karakousis CP, Balch CM, Urist MM, Ross MM, Smith TJ, Bartolucci AA. Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial. Ann Surg Oncol. 1996;3(5):446–52. doi: 10.1007/BF02305762. [DOI] [PubMed] [Google Scholar]
- 11.Moncrieff MD, Spira K, Clark JR, et al. Free flap reconstruction for melanoma of the head and neck: indications and outcomes. J Plast Reconstr Aesthet Surg. 2010;63(2):205–12. doi: 10.1016/j.bjps.2008.11.027. [DOI] [PubMed] [Google Scholar]
- 12.MacNeill KN, Ghazarian D, McCready D, Rotstein L. Sentinel lymph node biopsy for cutaneous melanoma of the head and neck. Ann Surg Oncol. 2005;12(9):726–32. doi: 10.1245/ASO.2005.11.028. [DOI] [PubMed] [Google Scholar]
- 13.Berman CG, Norman J, Cruse CW, Reintgen DS, Clark RA. Lymphoscintigraphy in malignant melanoma. Ann Plast Surg. 1992;28(1):29–32. doi: 10.1097/00000637-199201000-00010. [DOI] [PubMed] [Google Scholar]
- 14.Wells KE, Cruse CW, Daniels S, Berman C, Norman J, Reintgen DS. The use of lymphoscintigraphy in melanoma of the head and neck. Plast Reconstr Surg. 1994;93(4):757–61. doi: 10.1097/00006534-199404000-00016. [DOI] [PubMed] [Google Scholar]
- 15.Wasserberg N, Tulchinsky H, Schachter J, Feinmesser M, Gutman H. Sentinellymph-node biopsy (SLNB) for melanoma is not complication-free. Eur J Surg Oncol. 2004;30(8):851–6. doi: 10.1016/j.ejso.2004.06.021. [DOI] [PubMed] [Google Scholar]
- 16.Lin D, Franc BL, Kashani Sabet M, Singer MI. Lymphatic drainage patterns of head and neck cutaneous melanoma observed on lymphoscintigraphy and sentinel lymph node biopsy. Head Neck. 2006;28(3):249–55. doi: 10.1002/hed.20328. [DOI] [PubMed] [Google Scholar]
- 17.Gillgren P, Mansson-Brahme E, Frisell J, Johansson H, Larsson O, Ringborg U. Epidemiological characteristics of cutaneous malignant melanoma of the head and neck--a population-based study. Acta Oncol. 1999;38(8):1069–74. doi: 10.1080/028418699432383. [DOI] [PubMed] [Google Scholar]
- 18.Thorn M, Adami HO, Ringborg U, Bergstrom R, Krusemo U. The association between anatomic site and survival in malignant melanoma. An analysis of 12,353 cases from the Swedish Cancer Registry. Eur J Cancer Clin Oncol. 1989;25(3):483–91. doi: 10.1016/0277-5379(89)90261-7. [DOI] [PubMed] [Google Scholar]
- 19.Martinez SR, Chen SL, Bilchik AJ. Treatment disparities in Hispanic rectal cancer patients: a SEER database study. Am Surg. 2006;72(10):906–8. [PubMed] [Google Scholar]
- 20.Martinez SR, Robbins AS, Meyers FJ, Bold RJ, Khatri VP, Goodnight JE., Jr. Racial and ethnic differences in treatment and survival among adults with primary extremity soft-tissue sarcoma. Cancer. 2008;112(5):1162–8. doi: 10.1002/cncr.23261. [DOI] [PubMed] [Google Scholar]
- 21.Beal SH, Martinez SR, Canter RJ, Chen SL, Khatri VP, Bold RJ. Survival in 12,653 breast cancer patients with extensive axillary lymph node metastasis in the anthracycline era. Med Oncol. 2010 doi: 10.1007/s12032-009-9396-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Canter RJ, Beal S, Borys D, Martinez SR, Bold RJ, Robbins AS. Interaction of histologic subtype and histologic grade in predicting survival for soft-tissue sarcomas. J Am Coll Surg. 2010;210(2):191–198. doi: 10.1016/j.jamcollsurg.2009.10.007. e2. [DOI] [PubMed] [Google Scholar]
- 23.Leong SP, Accortt NA, Essner R, et al. Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients. Arch Otolaryngol Head Neck Surg. 2006;132(4):370–3. doi: 10.1001/archotol.132.4.370. [DOI] [PubMed] [Google Scholar]
- 24.Morton DL, Cochran AJ, Thompson JF, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242(3):302–11. doi: 10.1097/01.sla.0000181092.50141.fa. discussion 311-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Wells KE, Rapaport DP, Cruse CW, et al. Sentinel lymph node biopsy in melanoma of the head and neck. Plast Reconstr Surg. 1997;100(3):591–4. doi: 10.1097/00006534-199709000-00006. [DOI] [PubMed] [Google Scholar]
- 26.Ollila DW, Foshag LJ, Essner R, Stern SL, Morton DL. Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma. Ann Surg Oncol. 1999;6(2):150–4. doi: 10.1007/s10434-999-0150-0. [DOI] [PubMed] [Google Scholar]
- 27.O'Brien CJ, Uren RF, Thompson JF, et al. Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy. Am J Surg. 1995;170(5):461–6. doi: 10.1016/s0002-9610(99)80330-4. [DOI] [PubMed] [Google Scholar]
- 28.Jansen L, Koops HS, Nieweg OE, et al. Sentinel node biopsy for melanoma in the head and neck region. Head Neck. 2000;22(1):27–33. doi: 10.1002/(sici)1097-0347(200001)22:1<27::aid-hed5>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- 29.Tanis PJ, Nieweg OE, van den Brekel MW, Balm AJ. Dilemma of clinically node-negative head and neck melanoma: outcome of “watch and wait” policy, elective lymph node dissection, and sentinel node biopsy--a systematic review. Head Neck. 2008;30(3):380–9. doi: 10.1002/hed.20749. [DOI] [PubMed] [Google Scholar]
- 30.Willis AI, Ridge JA. Discordant lymphatic drainage patterns revealed by serial lymphoscintigraphy in cutaneous head and neck malignancies. Head Neck. 2007;29(11):979–85. doi: 10.1002/hed.20631. [DOI] [PubMed] [Google Scholar]
- 31.Doting EH, de Vries M, Plukker JT, et al. Does sentinel lymph node biopsy in cutaneous head and neck melanoma alter disease outcome? J Surg Oncol. 2006;93(7):564–70. doi: 10.1002/jso.20554. [DOI] [PubMed] [Google Scholar]
- 32.Pathak I, O'Brien CJ, Petersen-Schaeffer K, et al. Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern? Head Neck. 2001;23(9):785–90. doi: 10.1002/hed.1112. [DOI] [PubMed] [Google Scholar]
- 33.Ringborg U, Afzelius LE, Lagerlof B, et al. Cutaneous malignant melanoma of the head and neck. Analysis of treatment results and prognostic factors in 581 patients: a report from the Swedish Melanoma Study Group. Cancer. 1993;71(3):751–8. doi: 10.1002/1097-0142(19930201)71:3<751::aid-cncr2820710317>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
- 34.O'Brien CJ, Coates AS, Petersen-Schaefer K, et al. Experience with 998 cutaneous melanomas of the head and neck over 30 years. Am J Surg. 1991;162(4):310–4. doi: 10.1016/0002-9610(91)90138-4. [DOI] [PubMed] [Google Scholar]
- 35.Morselli P, Masciotra L, Pinto V, Zollino I, Brunelli G, Carinci F. Comparison Among Clark's, Breslow's, and TNM classifications for cutaneous head and neck malignant melanoma. J Craniofac Surg. 2007;18(6):1353–8. doi: 10.1097/scs.0b013e3180534453. [DOI] [PubMed] [Google Scholar]
- 36.Yu JB, Gross CP, Wilson LD, Smith BD. NCI SEER public-use data: applications and limitations in oncology research. Oncology (Williston Park) 2009;23(3):288–95. [PubMed] [Google Scholar]
- 37.Fisher SR. Cutaneous malignant melanoma of the head and neck. Laryngoscope. 1989;99(8 Pt 1):822–36. doi: 10.1288/00005537-198908000-00010. [DOI] [PubMed] [Google Scholar]
- 38.Epstein DS, Lange JR, Gruber SB, Mofid M, Koch SE. Is physician detection associated with thinner melanomas? JAMA. 1999;281(7):640–3. doi: 10.1001/jama.281.7.640. [DOI] [PubMed] [Google Scholar]