Abstract A33: Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor survival

Objective: A 31-gene expression profile (GEP) test that has been clinically validated identifies melanoma patients with low (Class 1) or high (Class 2) risk of metastasis based on primary tumor biology. This study aimed to prospectively evaluate the test impact on clinical management of melanoma patients.Methods: Physicians at 16 dermatology, surgical or medical oncology centers examined patients to assess clinical features of the primary melanoma. Recommendations for clinical follow-up and surveillance were collected. Following consent of the patient and performance of the GEP test, recommendations for management were again collected, and pre- and post-test recommendations were assessed to determine changes in management resulting from the addition of GEP testing to traditional clinicopathologic risk factors. Results: Post-test management plans changed for 49% (122 of 247) of cases in the study when compared to pre-test plans. Thirty-six percent (66 of 181) of Class 1 cases had a management change, compared to 85% (56 of 66) of Class 2 cases. GEP class was a significant factor for change in care during the study (p<0.001), with Class 1 accounting for 91% (39 of 43) of cases with decreased management intensity, and Class 2 accounting for 72% (49 of 68) of cases with increases.Conclusions: The reported study show that the 31-gene GEP test improves net health outcomes in the management of cutaneous melanoma. Physicians used test results to guide risk-appropriate changes that match the biological risk of the tumor, including directing more frequent and intense surveillance to high-risk, Class 2 patients.

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494 Heterogeneous mutational status of melanomas in multiple primary melanoma patients

Journal of Investigative Dermatology ◽

10.1016/j.jid.2016.06.516 ◽

2016 ◽

Vol 136 (9) ◽

pp. S244

Author(s):

C. Pellegrini ◽

C. Martorelli ◽

G. Cipolloni ◽

L. Di Nardo ◽

A. Antonini ◽

...

Keyword(s):

Primary Melanoma ◽

Mutational Status ◽

Multiple Primary ◽

Melanoma Patients

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Do Oncologic Outcomes From Head and Neck Versus Truncal and Extremity Melanoma Differ? A Single-Institution Single-Subspecialty Experience

The American Surgeon ◽

10.1177/00031348211050813 ◽

2021 ◽

pp. 000313482110508

Author(s):

Kirsten M Baecher ◽

Michael K Turgeon ◽

Caroline R Medin ◽

Geetha Mahendran ◽

Terrill M Flakes ◽

...

Keyword(s):

Head And Neck ◽

Primary Melanoma ◽

High Volume ◽

Oncologic Outcomes ◽

Single Institution ◽

Tertiary Referral Center ◽

Definitive Evidence ◽

Multivariable Analyses ◽

Melanoma Patients ◽

Eighth Edition

Background Outcomes are thought to be worse in head and neck (H&N) melanoma patients. However, definitive evidence of inferior outcomes in H&N melanoma in the modern era is lacking. We sought to ascertain whether H&N melanomas carry a worse prognosis than melanomas of other sites. Methods All patients who underwent excision for primary melanoma by fellowship-trained surgical oncologists at a single institution from 2014 to 2020 were queried from the electronic medical record. Patients who had AJCC eighth edition stage I-III disease were included. Results Of 1127 patients, 28.7% had primary H&N melanoma. H&N patients were more likely to be male, older, and present with more advanced AJCC stage. Median follow-up was 20.0 months (IQR 26.4). On multivariable analyses controlling for other variables, H&N melanoma was associated with worse RFS. Notably, H&N melanoma was not associated with worse MSS, DMFS, or OS on univariate or multivariable analyses. Among patients who recurred, H&N patients were significantly more likely to recur locally compared to non-H&N patients. On subgroup analysis, scalp melanoma was also associated with worse RFS compared to patients with melanoma in locations other than the scalp. When patients with scalp melanoma were excluded from analysis, non-scalp H&N RFS was not significantly different from the non-H&N group on univariate or multivariable analyses. Discussion In this series from a high-volume tertiary referral center, the differences in rates and sites of recurrence between H&N and non-H&N melanoma do not impact melanoma-specific or overall survival, suggesting that H&N melanoma patients should be treated similarly with respect to regional and systemic therapies.

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Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919848872 ◽

2019 ◽

Vol 11 ◽

pp. 175883591984887 ◽

Cited By ~ 5

Author(s):

Lorena Incorvaia ◽

Giuseppe Badalamenti ◽

Gaetana Rinaldi ◽

Juan Lucio Iovanna ◽

Daniel Olive ◽

...

Keyword(s):

Immune Response ◽

Overall Survival ◽

Survival Rate ◽

Metastatic Melanoma ◽

Braf Mutation ◽

Primary Melanoma ◽

Tumor Infiltrating Lymphocytes ◽

Enzyme Linked Immunosorbent Assay ◽

Melanoma Patients ◽

Infiltrating Lymphocytes

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.

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Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human

Cancers ◽

10.3390/cancers12051094 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1094 ◽

Cited By ~ 1

Author(s):

Ludovic Jean Wrobel ◽

Angèle Gayet-Ageron ◽

Frédérique-Anne Le Gal

Keyword(s):

Immune Response ◽

Immune Cell ◽

Wide Spectrum ◽

Beta Blockers ◽

Primary Melanoma ◽

Progression Free Survival ◽

Human Melanoma ◽

Clinical Models ◽

Melanoma Patients ◽

Control Disease

Background: The regulation of melanoma by noradrenergic signaling has gain attention since pre-clinical and clinical studies suggested a benefit of using beta-blockers to control disease progression. We need to confirm that human melanoma recapitulates the mechanisms described from pre-clinical models. Methods: The sources and targets of norepinephrine in the microenvironment of 20 human melanoma samples was investigated using immunostaining. The effect of an exposure to beta-blockers on immune cell type distribution and expression of immune response markers was assessed with immunostaining on 212 human primary melanoma. A statistical analysis explored the effect of an exposure to beta-blockers on progression free survival, melanoma related survival, and overall survival on the 286 eligible patients. Results: Tumor cells and macrophages may be a source of norepinephrine in melanoma microenvironment. Tumors from patients exposed to wide spectrum beta-blockers recapitulate the increased infiltration of T-lymphocytes and the increased production of granzyme B observed in pre-clinical models. An exposure to beta-blockers is associated with a better outcome in our cohort of melanoma patients. Conclusion: This study shows the association between an exposure to wide spectrum beta-blockers and markers of an effective anti-tumor immune response as well as the protective effect of beta-blockers in human melanoma patients.

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TERT Promoter Mutations are Associated with Visceral Spreading in Melanoma of the Trunk

Cancers ◽

10.3390/cancers11040452 ◽

2019 ◽

Vol 11 (4) ◽

pp. 452 ◽

Cited By ~ 5

Author(s):

Simona Osella-Abate ◽

Luca Bertero ◽

Rebecca Senetta ◽

Sara Mariani ◽

Francesco Lisa ◽

...

Keyword(s):

Logistic Regression ◽

External Validation ◽

Multivariate Logistic Regression Analysis ◽

Primary Melanoma ◽

Control Group ◽

Tert Promoter ◽

Mutational Status ◽

Tert Promoter Mutations ◽

Melanoma Patients ◽

Promoter Mutations

Survival predictions are currently determined on the basis of NRAS/BRAF mutations, even though TERT promoter mutations have been recently associated with a poor prognosis in stage I-II melanomas. Usually, it is not recommended to perform a mutational test on primary melanoma, as the results do not always reflect the mutational status of metastases. In particular, trunk melanomas have been reported to have an unfavourable prognosis. A series of 105 advanced melanoma patients were analysed by TERT promoter Sanger sequencing. Univariate/multivariate binary logistic regression models were performed using progression to a visceral site as the dependent variable and patient/tumour characteristics as covariates. Performance of the model was assessed in an external independent primary melanoma patients’ dataset. Male gender (odds ratio (OR), 344; 95% CI, 1.12–10.6; p = 0.031), AJCC (American Joint Committee on Cancer) classification (OR, 022; 95% CI, 0.07–0.67; p = 0.008), SLNB (Sentinel Lymph Node Biopsy) status (OR, 3.05; 95% CI, 1.06–8.78; p = 0.039) and TERT-mutated trunk lesions (OR, 3.78; 95% CI, 1.35–10.6; p = 0.011) were significantly associated with the risk of developing a visceral spreading as first site of progression using multivariate logistic regression analysis. These results were confirmed in the external validation control group. Therefore, in trunk primary melanomas, due to their high risk of progression to visceral sites, we encourage somatic TERT mutation analysis at diagnosis to identify those patients who would potentially benefit from a more intensive follow-up protocol and a prompt initiation of therapy.

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Prospective analysis of predictors of survival in melanoma patients with brain metastases

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9074 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9074-9074

Author(s):

J. A. Zakrzewski ◽

L. Geraghty ◽

H. Hamilton ◽

P. Christos ◽

D. Krich ◽

...

Keyword(s):

Brain Metastases ◽

Mitotic Index ◽

Primary Tumor ◽

Univariate Analysis ◽

Primary Melanoma ◽

Neurological Symptoms ◽

Independent Effect ◽

Exclusion Criterion ◽

Clinical Variables ◽

Melanoma Patients

9074 Background: Melanoma patients (pts) with brain metastases (BM) have limited survival, and BM remains an exclusion criterion in most clinical trials. A recent retrospective analysis at Memorial Sloan Kettering Cancer Center (MSKCC) identified 4 clinical variables that were associated with worse post BM survival (Raizer J et al, Neuro Oncol 2008). In this study, we investigated whether primary tumor features could improve the predictability of post BM survival and examined the reproducibility of the variables identified in MSKCC study. Methods: Melanoma pts with BM prospectively enrolled in an interdisciplinary database at NYU Medical Center from 2002 to 2008 were studied. Six primary tumor characteristics, 21 clinical variables, and treatments were examined. Univariate associations were analyzed using Kaplan Meier survival analysis and the independent effect of identified predictors was assessed by multivariate cox proportional hazards regression analysis. Results: Eighty-nine pts (36 F, 53 M, median age 57) were identified. Median post BM survival was 5.75 months. Median follow-up time based on survivors was 4.2 months. Ulceration and mitotic index ≥3/field were univariately associated with worse post BM survival (p=0.004, p=0.009 respectively). Age >65, ≥3 BM lesions, presence of neurological symptoms, and extracranial metastases were also univariately associated with worse post BM survival (the same 4 variables identified in MSKCC retrospective study). An additional 4 clinical parameters were significant by univariate analysis: frontal lobe location (p=0.01), bilateral lesions (p=0.01), ≥2 neurological symptoms (p=0.005), and weakness/fatigue (p<0.0001). After reproducing the significance of the 4 MSKCC variables in a multivariate model, ulceration of the primary tumor was also an independent predictor of post BM survival (hazard ratio [HR] = 2.75; 95% CI = 1.30, 5.83; p=0.008) whereas mitotic index ≥3/field was not (HR=1.24; 95% CI = 0.57, 2.71; p=0.59). Conclusions: Data suggest that ulceration of the primary melanoma might indicate an adverse biologic behavior that impacts post BM survival. Our data also lend independent support for the predictive model of post BM survival. No significant financial relationships to disclose.

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Second primary melanoma: Risk factors, histopathologic features, and survival

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9073 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9073-9073

Author(s):

H. F. Schoellhammer ◽

H. Torisu-Itakura ◽

Y. Huynh ◽

M. Sim ◽

M. B. Faries ◽

...

Keyword(s):

Primary Melanoma ◽

Breslow Thickness ◽

Second Primary ◽

Clark Level ◽

Ajcc Stage ◽

Melanoma Patients ◽

Level I ◽

Second Primaries

9073 Background: Melanoma incidence in the United States is expected to be 4.3% of all cancers in 2008. Cutaneous melanoma patients are at risk for second primary melanoma development. Our goal was to characterize the histopathologic features, risk factors, and patient survival for second primary melanoma. Methods: A review of the melanoma database established in 1971 at John Wayne Cancer Institute was conducted identifying patients with American Joint Committee on Cancer (AJCC) stage I and II cutaneous melanoma who later developed a second primary melanoma. Patients were grouped by Breslow thickness, Clark level, and histopathologic subtype (superficial spreading [SSM], nodular, acral lentiginous, lentigo maligna, and in situ). Multivariate analysis involving age, gender, Breslow thickness, Clark level, and ulceration status was performed to determine an effect on development of second primary. Kaplan-Meier survival curves were plotted for single primary and second primary melanoma patients. Results: Second primary melanoma was identified in 411 (3.7%) of 10,968 patients with AJCC stage I-II melanoma. The most common first primary subtype was SSM, and 93% of these patients had in situ or SSM as the second primary. Sixty-five percent of first primaries had a Breslow thickness of ≤1 mm, and 75% of second primaries had a thickness ≤1 mm. Forty-nine percent of first primaries had Clark level I or II, but 68% of second primaries had Clark level I or II. In multivariate analysis, only increasing age was significantly associated with the likelihood of second primary melanoma (p<0.0001). With increasing follow-up time the hazard ratio of second primary melanoma was 1.31 for every decade. Overall survival for second primary melanoma patients was better than for single primary patients (p<0.0001). Conclusions: Most second primary melanoma patients will have SSM or in situ, with a decreased Clark level and Breslow thickness. Contrary to expectations, patients developing second primary melanoma did not exhibit decreased overall survival. Increased follow-up time after first primary melanoma is a significant risk factor for second primary development, thus illustrating the importance of lifelong patient follow-up. No significant financial relationships to disclose.

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Sentinel node biopsy in melanoma patients: The role of day surgery and local anaesthetic approach for quality-of-life and effective cost reduction.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19002 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19002-e19002

Author(s):

Fabio Ricci ◽

Erminio Saralli ◽

Loreto Giovanni Capuano ◽

Maurizio Dorkin ◽

Mario Valleriani ◽

...

Keyword(s):

Quality Of Life ◽

Sentinel Node ◽

Sentinel Node Biopsy ◽

Cost Reduction ◽

Primary Melanoma ◽

Day Surgery ◽

Blue Dye ◽

Node Biopsy ◽

Melanoma Patients

e19002 Background: Sentinel node biopsy (SNB) is used in the management of melanoma patients without nodal metastases. Methods: From January 1, 1998 to December 31, 2011 we performed 182 SNBs at St. M. Goretti Hospital. Patients presented a primary melanoma, Breslow thickness equal to or higher than 1 mm, lower than 1 mm with regression and/or ulceration, and/or IV-V Clark level, and/or mitotic rate ≥ 1/mm2, according to the 7th edition melanoma staging system. All patients underwent pre-operative lymphoscintigraphy with intradermal injection of 50-70 MBq 99 mTc colloidal albumina particles, 50-80 nm size range, in 0.1-0.2 ml saline solution. We never used blue dye. All patients underwent surgical treatment 4-12 h. later. We performed SNB in day-surgery (DS) under local anaesthesia (LA). Surgery incision was 3-4 cm. This study was approved by an ethics committee, discussed with all patients and informed consent was obtained. Purpose of the study is to investigate the validity of this approach for quality of life and cost reduction. Results: 165 patients underwent SNB, 64 (38.7%) in the inguinal region, 83 (50.3%) in axilla, 1 (0.6%) in the popliteal region, 4 (2.4%) patients showed inguinal bilateral sentinel lymph-node (SLN), 6 (3.6%) axillary bilateral SLN, 4 (2.4%) axillary and 3 (1.8%) inguinal double SLN. The SLN identification rate was 100%. After surgery we distributed a questionnaire to the patients about the acceptability of this approach. In 32 patients SLN was positive. In these patients we performed radical lymphoadenectomy, 12 (37.5%) inguinal and 20 (62.5%) axillary. Conclusions: The results achieved are extremely accurate. This procedure is safe, well accepted by patients (98%), reported better quality of life. The oncological results are absolutely reliable. As regards hospital logistics, operations in DS and LA can be easily managed, leading to a significant cost reduction, 42.15% less expensive than the same operation performed under general anaesthesia.

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