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Malignant Melanoma in the Elderly: Different Patient or Different Disease?
John Smetona1, Daniel C. Sasson1, Yassmin Parsaei1, Marianna Papageorge1, Stephen Aryan1, Kelly Olino2, James Clune1
1Yale Plastic and Reconstructive Surgery, New Haven, Connecticut, United States, 2Surgery, Yale, New Haven, Connecticut, United States

Objective:
To compare the clinical outcomes of older and younger patients with melanoma
To assess for differences in tumor genetic makeup that might explain differences in clinical behavior between older and younger cohorts

Design:
This was a retrospective cohort review of the patients enrolled in the melanoma database at a single institution from 1984 to 2019.

Setting:
This study was conducted at a regional, academic referral center. Typically patients present and are treated in the ambulatory setting.

Patients:
A consecutive sample of all patients in the selected age ranges diagnosed with melanoma between 1984 and 2019 were included in our study. Patients were categorized by age into younger (20-40 years at time of diagnosis) and older (70-100 years) cohorts. 1,740 patients were included, with 1,285 in the older cohort and 455 in the younger cohort. Tumor genetic data was available for 203 patients.

Interventions:
Melanoma treatment was provided in accordance with the standard of care

Main Outcome Measures:
Melanoma-specific mortality at 5 and 10 years
Melanoma recurrence at 5 and 10 years
Chi-squared and Fisher exact tests were used to compare event rates between older and younger groups.
Kaplan Meier Curves were generated to account for attrition.

Results:
At the time of diagnosis, the older group had a higher incidence of thicker and ulcerated tumors (P < .05), and lower nodal positivity (T1 tumors .2% vs 1.7%; T2 5.4% vs 13%; T3 15% vs 30%; and T4 16% vs 54%) (p< .05).

Recurrence was equivalent between older and younger cohorts when matched for Breslow thickness. 5- and 10-year melanoma-specific survival were lower in the older group (92% vs 98% at 5 years; 91% vs 94% at 10 years, P < .05). At a given Breslow thickness, melanoma-specific mortality was equivalent between older and younger cohorts except for T2 tumors at 5 years (older group 95%, younger group 99%, p <.05). Kaplan Meier analysis showed equivalence in survival at all Breslow thicknesses when assessed from 0 to 15 years, but a higher melanoma-specific survival for the younger cohort in aggregate. Time to recurrence (2.1 vs 5.9 years) and mortality (3.2 vs 7.9 year) were less for the elderly.

BRAF was mutated in 29% of older patients vs 63% of younger patients (p < .00001), while NRAS was mutated in 32% of older patients vs 11% of younger patients (p = .0303).

Conclusions:
Older patients presented with more aggressive tumor characteristics but lower nodal positivity. Recurrence and melanoma-specific mortality were higher and occurred sooner; however, recurrence and mortality were equivalent when Breslow thickness was matched. Differences in genetic profile and rates of nodal positivity suggest differences in pathologic processes in older patients. Further study is required to fully elucidate the genetic mechanisms underlying this behavior and to differentiate genetic vs clinical drivers of mortality discrepancy.


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