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Impact of age on the management of primary melanoma patients.

ABSTRACT: Age is an understudied factor when considering treatment options for melanoma. Here, we examine the impact of age on primary melanoma treatment in a prospective cohort of patients.We used logistic regression models to examine the associations between age and initial treatment, using recurrence and melanoma-specific survival as endpoints.444 primary melanoma patients were categorized into three groups by age at diagnosis: 19-45 years (24.3%), 46-70 (50.2%), and 71-95 (25.5%). In multivariate models, older patients experienced a higher risk of recurrence (hazard ratio 3.34, 95% confidence interval, CI, 1.53-7.25; p < 0.01). No significant differences were observed in positive biopsy margin rates or extent of surgical margins across age groups. Patients in the middle age group were more likely to receive adjuvant therapy than those in the older group (odds ratio 2.78, 95% CI 1.19-6.45; p = 0.02) and showed a trend to longer disease-free survival when receiving adjuvant therapy (p = 0.09).Our data support age as an independent negative prognostic factor in melanoma. Our data suggest that age does not affect primary surgical treatment but may affect decisions of whether or not patients receive postoperative treatment(s). Further work is needed to better understand the biological variables affecting treatment decisions and efficacy in older patients.

SUBMITTER: Fleming NH

PROVIDER: S-EPMC3842185 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Impact of age on the management of primary melanoma patients.

Fleming Nathaniel H NH Tian Jiaying J Vega-Saenz de Miera Eleazar E Gold Heidi H Darvishian Farbod F Pavlick Anna C AC Berman Russell S RS Shapiro Richard L RL Polsky David D Osman Iman I

Oncology 20130830 3

<h4>Objectives</h4>Age is an understudied factor when considering treatment options for melanoma. Here, we examine the impact of age on primary melanoma treatment in a prospective cohort of patients.<h4>Methods</h4>We used logistic regression models to examine the associations between age and initial treatment, using recurrence and melanoma-specific survival as endpoints.<h4>Results</h4>444 primary melanoma patients were categorized into three groups by age at diagnosis: 19-45 years (24.3%), 46- ...[more]

PMID: 24008821

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Project description:Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers.We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015. We used Kaplan-Meier and Cox regression analyses to assess OS and PFS and identify factors associated with these outcomes. We also compared rates of autoimmune toxicity across age groups.Of 254 patients, 57 (22.4%) were <50 years old, 85 (33.5%) were age 50-64, 65 (25.6%) were age 65-74, and 47 (18.5%) were ?75 years. Across age groups, no differences existed in median OS (age <50: 22.9 months, age 50-64: 25.3 months, age 65-74: 22.0 months, age ?75: 24.3 months) or PFS (age <50: 4.1 months, age 50-64: 6.5 months, age 65-74: 5.4 months, age ?75: 7.9 months). The presence of liver metastases and elevated pre-treatment lactate dehydrogenase (LDH) were associated with reduced OS. Presence of liver metastasis, pretreatment LDH, BRAF mutation, and type of melanoma correlated with PFS. Overall, 110 patients (43.3%) experienced immune-mediated toxicities; 25 (9.8%) had colitis and 26 (10.2%) had endocrine toxicity. Rates of colitis, hepatitis, and pneumonitis did not differ across age groups.We demonstrated that patients could safely tolerate anti-PD1/PDL-1 mAb therapy and achieve similar outcomes regardless of their age.Immunotherapy has revolutionized treatment for patients with metastatic melanoma, yet data are lacking regarding the effectiveness and tolerability of these treatments for older patients. In this study, we demonstrated that patients with melanoma safely tolerate immunotherapy and achieve similar outcomes regardless of their age. Specifically, we utilized data from two academic cancer centers and found no significant difference in overall survival, progression free survival, or immune-related toxicities, other than arthritis, across age groups. As the population ages, studies such as this will become critical to help us understand how best to treat older adults with cancer.

Project description:BackgroundTwo primary histologic subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM), comprise the majority of all cutaneous melanomas. NM is associated with worse outcomes, which have been attributed to increased thickness at presentation, and it is widely expected that NM and SSM would exhibit similar behavior once metastasized. Herein, we tested the hypothesis that primary histologic subtype is an independent predictor of survival and may impact response to treatment in the metastatic setting.MethodsWe examined the most recent Surveillance, Epidemiology, and End Results (SEER) cohort (n = 118 508) and the New York University (NYU) cohort (n = 1621) with available protocol-driven follow-up. Outcomes specified by primary histology were studied in both the primary and metastatic settings with respect to BRAF-targeted therapy and immunotherapy. We characterized known driver mutations and examined a 140-gene panel in a subset of NM and SSM cases using next-generation sequencing. All statistical tests were two-sided.ResultsNM was an independent risk factor for death in both the SEER (hazard ratio [HR] = 1.55, 95% confidence interval [CI] = 1.41 to 1.70, P < .001) and NYU (HR = 1.47, 95% CI = 1.05, 2.07, P = .03) cohorts, controlling for thickness, ulceration, stage, and other variables. In the metastatic setting, NM remained an independent risk factor for death upon treatment with BRAF-targeted therapy (HR = 3.33, 95% CI = 1.06 to 10.47, P = .04) but showed no statistically significant difference with immune checkpoint inhibition. NM was associated with a higher rate of NRAS mutation (P < .001), and high-throughput sequencing revealed NM-specific genomic alterations in NOTCH4, ANK3, and ZNF560, which were independently validated.ConclusionsOur data reveal distinct clinical and biological differences between NM and SSM that support revisiting the prognostic and predictive impact of primary histology subtype in the management of cutaneous melanoma.

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Impact of age on the management of primary melanoma patients.

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Impact of age on the management of primary melanoma patients.

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