ASSOCIATION BETWEEN PRIMARY SITE OF MELANOMA AND SURVIVAL OF U.S. ADULT PATIENTS

Algarni Ali 1 ,Al-OmariNaif 1 , Acuna Juan 2 and Sami Aldaham 1 . 1. Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Saudi Arabia. 2. Florida International University (FIU), United States. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


Introduction:-
Melanoma is the most dangerous form of skin cancer that represents 4.6% of all new cancer cases in the United States. The National Cancer Instituteestimated that there would be 76,100 new invasive melanoma cases and 9,710 deaths from melanoma in the United States in 2014 [1,2]. Anatomic location was identified as a significant prognostic factor in patients with primary cutaneous melanoma (CM) by several investigators. [3,4,5,6]. Understanding the role of anatomic site in melanoma survival is important for public health messages on skin awareness and sun protection. Moreover, because the role of screening in melanoma is considered important for early detection [7,8]. The location often has been classified into four anatomic regions: head and neck, trunk, and the upper and lower extremities [9,10,11,12]. But some authors have tried to subdivide anatomic location into higher and lower risk sites according to recurrence or survival rates [5,13.14,15]. Cutaneous head and neck melanomas (CHNM) constitute 12-21% of melanomas diagnosed annually [16,17]. CHNM have poorer outcomes relative to melanomas of other sites (MOS) [18,19,20].Extremity lesions have generally been associated with a more favourable prognosis than trunk and head and neck lesions, even when adjusted for tumour type and thickness [21,22].Other authors have confirmed that the anatomical location is a prognostic factor, but have demonstrated a poor prognosis in association with other areas, such as the BANS region (upper back, posterior arm, neck and posterior scalp) [23].

Objectives:-
The aim of this study is to assess the relationship between primary site of melanoma and survival in a large US adult population. and melanoma specific survival (MSS) dependent on location of tumor. Result shown that ten-year overall survival was 55.1% for all patients with cutaneous head and neck melanoma. For tumors of the scalp/neck, 10-year rates of overall survival was 57.2%. 10-year overall for cutaneous head and neck melanoma (CHNM) at sites other than the scalp/neck was 55.6%. the author concluded that 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 [24]. Claus Garbe, et al discussed Prognostic Classification of Anatomic Location of Primary Cutaneous Melanoma. In a series of 5093 patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at four university centers in Germany who were investigated using the multivariate Cox proportional hazard model to analyze the importance of anatomic location for survival probability. The back and breast (thorax), upper arm, neck ,and scalp (TANS regions) were identified as high risk sites as the univariate 10-year survival rates for primary CM showed significant site-related differences ranging from 63.4% (scalp), 68% (back) to 87.7% (lower arm), 82.4% (lower leg). The author concluded that the Anatomic location was confirmed as an independent prognostic factor for patients with primary cutaneous melanoma. The TANS regions were identified as high risk sites, and the lower trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as intermediate sites [25].

H. M. SHAW, et al discussed Influence of Site of Lesion and Age of Patient in the Female Superiority in Survival.
Statistical analyses of differences between survival rates were carried out by the Logrank method. Observed and expected differences were analyzed for significance by the chi-square test with one degree of freedom. final group comprised 753 patients (362 men and 391 women). Result showed that Melanoma of extremities had better prognosis than axial melanoma with 5-yr survival (<1.5mm thick) of 85.7% in men and 96.8 % in women. as opposed to axial melanoma 5-yr survival (<1.5mm thick) of 75.7% in men and 84.3% in women. The author concluded that The association between decline in prognosis with increasing age and decline in proportion of thin lesions with increasing age was much closer in men than women. In men and women matched by age, site, and thickness of primary lesions, women with very thick tumors still survived longer [26].

Material & Method:-
In this study our population was 249175 US melanoma patientsfrom the SEER (Surveillance, Epidemiology, and End Results Program Registry) during the 1973 to 2011 period. Weexcluded 20366 patients as duplicated cases and 2068 1300 patients younger than 18 years old.The final group was 227509 US melanoma patients, we analyzed themusing SPSS[ Figure 1]. We used Kaplan-Meier curves to compare primary sites and survival with 5 years interval [Figure2]. Hazard ratio (HR) were determined by unadjusted and adjusted Cox-regression model.  Table 1] Patients who survived 5 years or less are older (61.3) compare to those who survived more than 5 years. Patient with primary sites of melanoma located at lower limb/hip and trunk have higher percentage in more than 5 year category (63.9% and 63.5% respectively). While patients with primary site defined as overlapping lesion of skin and skin NOS have the lower percentage (26.5%) of surviving more than 5 years. Women diagnosed with melanoma have better higher percentage of surviving after 5 years compared with men (64.8% and 53.8% respectively). Patients diagnosed at early stage (63.7%) have more probability of surviving 5 years or more than those at late stage (36.3%). [ Table 2] In our unadjusted model the primary site was significantly associated with the survival. Melanoma patients whose primary site was overlapping lesion of skin/skin NOS are 10 times more likely to die due to melanoma compared to patients with lesions at head/neck (HR= 0.772). Women are 60% less likely to die from melanoma compared with men. Patients diagnosed at late stage are have worse prognosis in comparison to those diagnosed at early stage (HR= 11.229).
After we adjusted for age and stage at diagnosis, gender, race and ethnicity, overlapping lesion of skin/skin NOS and lower limb/hip were highly associated with unfavorable prognosis of melanoma compared to head/neck (HR= 3.500 and HR=1.900 respectively). Women are still less likely to die from melanoma compared with men (H=0.600). Patients who have the worst prognosis for melanoma are those diagnosed at late stage (HR=8.900) and white patients (HR=1.200). [ Table 3] Less than 10% of overlapping lesions patients survived 60 months. Around 43% of trunk and lower limbs and hip patients survived 60 months.Upper limb and shoulder and head and neck patients had the highest percentage of surviving 60 months by more than 50%. [ Figure 4]

Conclusions:-
This study have shown a very obvious difference in survival between the primary sites. Overlapping lesion of skin had the worst prognosis followed by trunk lesions while upper limb & shoulder lesions have a better prognosis. Timely diagnosis of primary melanoma sites will improve survival and prognosis of this population.