Melanoma and Cutaneous Oncology

The department of melanoma and cutaneous oncology is focused on understanding the molecular mechanisms of recurrence in early and late stages of skin cancers. Specifically, we are interested in blood and tumor biomarkers that can predict the risk of developing metastases.

Melanoma and Cutaneous Oncology - Saint John's Cancer Institute

Mission and Vision

The mission and vision of the department of Melanoma and Cutaneous Oncology is to understand the molecular mechanism of disease metastases and recurrence of skin cancers, focusing primarily on melanoma.

Our goal is to identify blood and tumor biomarkers to assess the risk of recurrence then use such information for the benefit of the patient. Indeed, developing tools to predict development of metastases would enhance the methods of following up post-surgical melanoma patients, allowing for more effective and focused surveillance. Ultimately, this will improve patient survival by allowing earlier treatment for patients with predicted recurrence.

Melanoma Research Saint John's Cancer Institute

Understanding Risk

Most new melanoma cases are diagnosed at early stages, 75% and 15% stage I and II, respectively.  Standard of care for these patients is excision of the primary tumor then regular follow-ups. While most patients are cured by surgical resection of the primary tumor, some of them will develop metastases decreasing survival from 90% to 20-25%. Thus, there is a need to accurately identify patients with high risk of developing metastases.

Today, prognosis and risk of recurrence are estimated based on the primary tumor characteristics and for presence of sentinel lymph node metastases which is often unreliable. Indeed, up to 21% of patients with tumor-negative lymph node will develop metastases, and up to 50% of tumor-positive lymph node patients will not. As a result, early-stage melanoma patients require expensive life-long follow-up and suffer the anxiety and costs of repeated physician visits. Thus, there is a need to develop accurate individual prognostic tools.

Partnerships & Collaboration

Our lab is engaged in several collaborative studies with Saint john’s Cancer Institute (SJCI) faculty members and external research institutes. For example, we have developed collaborative projects with Cedars-Sinai pathologists which involves the transfer of pathology slides, paraffin tissue specimens, and data from SJCI. These exchanges help to foster research and findings that are commonly expressed though co-authored publications.

 

Partnerships and Collaboration - Saint John's Cancer Institute

Current Research Topics

The laboratory focuses on recurrence of skin cancers at the molecular level. We are currently developing new approaches to identify blood and tumor biomarkers that can predict development of metastases in stage I-II melanoma patients and re-occurrence of metastases after surgery in advanced stages. Using molecular, imaging, and bio-informatics approaches, we are developing tools that will help clinicians better determine the patients’ prognosis and adapt their clinical approach accordingly.

Ongoing Projects

Micro RNA Expression Revealing Future Metastases
A heatmap reveals Micro RNA (miRNA) Signature in recurrence and no recurrence groups, revealing increased expressions where colors darken.

Serum microRNAs to predict early recurrence in stage I-II patients

MicroRNAs are small non-coding RNA molecules that can be found in various biological fluids such as blood .Due to their roles in various cellular processes MicroRNAs can be used for diagnosis and prognosis. Our goal is to identity miRNAs present in the serum at the time of diagnosis that can predict early recurrence/development of metastases. MicroRNAs are small non-coding RNA molecules that can be found in various biological fluids such as blood .Due to their roles in various cellular processes MicroRNAs can be used for diagnosis and prognosis.

Using primary tumor to predict distant metastases

The 10-year survival rates range for stage I-II melanoma patients is close to 98%. However, once metastases occur, the 10-year survival diminishes to 20-25%. Thus, there is a need to identify early patients who will develop metastases. This will help clinicians accurately adapt the follow up schedule and provide early access to systemic therapy for high risk patients.

Working with primary melanoma tumor samples collected during wide excision surgery with long term follow up, we have recently identified 4 immune-modulating genes as predictors of metastases. The preliminary data showed that these 4 genes are predictive of the development of distant metastases. Using Quantitative Polymerase Chain Reaction (qPCR) technique, and RNA in Situ Hybridization (RNA-ISH), confirmation of these preliminary results is actively underway.

Future Projects

Predicting recurrence in melanoma patients

Based on our studies on miRNAs in serum and immune modulating genes in primary tumors we will assess how these biomarkers can be combined more accurately. This will help us to study molecular mechanisms that lead to melanoma metastases. Preliminary results showed that these biomarkers, also found in lymph nodes, could be predictive of recurrence, we intend to confirm these findings.

Recurrence after lung metastases resection

Until recently, surgical resection of metastases was the primary treatment for metastatic melanoma patients. The advent of modern systemic therapy shifted this treatment model, greatly improving these patients’ prognoses. Our pilot study showed that patients with lung metastases had improved survival when pulmonary resection is combined with modern systemic therapy. However, for some patients with surgery only present a good outcome. We intend to assess which tumor characteristics and immune mechanisms are involve in such cases.

Manuscripts in Development

1.Logistic Regression Modeling as a First Step for Machine Learning to Guide the Surgical Care of Early-Stage Melanoma

Anthony J. Scholer, MD
Mary Garldand-Kledzik, MD
Li Hsing-Fang, Ph.D.
Stacey L. Stern, BS
Juan Santamaria-Barria, MD
Adam Kader, MD
Trevan D. Fischer, MD
Leland Foshag, MD
Richard Essner, MD

Summary: The objective of this study was to create a validated logistic-regression model to predict the Sentinel Lymph Node status (SLN), given that it is the most significant predictor of recurrence and melanoma-specific survival. The SLN logistical-regression model is the first step toward devising an integrated machine learning algorithm that uses predictive analytics for the personalized care of early-stage melanoma. This machine-learning algorithm can help physicians by providing personalized risk assessments to support challenging clinical decisions.

2. Is therapeutic lymph node dissection of value for lymph node recurrence in melanoma?

Ana K. Wilson MS, DO
Stacey L. Stern, BS
Patrick D. Lorimer, MD
Leland J. Foshag, MD
Richard Essner, MD
Nathanial A. Lee, MD
Judi B. Ramiscal, MD
Trevan D. Fischer, MD

Summary: This study evaluated the potential survival benefit of Therapeutic Lymph Node Dissection (TLND) in patients with nodal recurrence following a previously negative sentinel lymph node dissection. Although complete lymphadenectomy is no longer recommended for patients with tumor positive sentinel lymph nodes, TLND is still recommended for patients with lymph node recurrences. By utilizing our institutional melanoma database of over 15,000 patients and data from previous clinical trial, we successfully identified patients with nodal recurrences following a tumor-negative sentinel lymph node biopsy. Findings revealed that TLND did not improve Distant Metastasis-free Survival (DMFS) and Melanoma Specific Survival (MSS) in patients with lymph node recurrence. Interestingly, some patients who had biopsy alone had multiple lymph nodes involved, yet still had similar outcomes to patients with one tumor positive node treated with TLND. This data further suggests a lack of therapeutic value for TLND in melanoma.

3. Contemporary Management of Lung Metastasis in Melanoma

Judi Anne B. Ramiscal, MD
Richard Essner, MD
Stacey L. Stern, BS
David Shih
Ashton J. Rosenbloom
Kristel A. Lourdault, PhD

Summary: This study evaluated survival in American Joint Committee on Cancer (AJCC) stage IV melanoma patients with lung metastases who underwent metastatic resection alone, or in combination with modern systemic therapy. Until recently, surgical removal of metastases was the primary treatment for metastatic melanoma patients. Modern systemic-targeted and immunotherapy produced improved prognoses. This retrospective review of our institutional database included patients diagnosed with AJCC stage IV melanoma with pulmonary tumor(s) from 2005 to 2018 with documented metastatic surgical resection and/or BRAF/MEK targeted treatment or immunotherapy. The study suggests that pulmonary resection in metastatic melanoma remains essential to the management of patients, however, a more dedicated study must be conducted to define the value of surgery in terms of patient selection, timing, and combination strategies for these patients.

Meet Our Team

Dr. Richard Essner, MD. FACS., Professor of Surgery, Director of Surgical Oncology & Co-Director of Melanoma and Cutaneous Oncology Research Program, serves as Principal Investigator alongside Kim Margolin, M.D., FACP, FASCO, and Maria L. Ascierto, Ph.D., who are supported by an exceptional team of scientists, program specialists, and associates.  Together, they work to understand the predictors and mechanism of melanoma metastases and treatment.

Cutaneous Team - Saint John's Cancer Institute

Publications

Dr. Richard Essner has published and co-authored more than 100 peer-reviewed publications. See full list at NIH.gov

  1. The association between facility volume and overall survival in patients with Merkel cell carcinoma.
  2. Prevalence of Delta-Like Protein 3 Expression in Merkel Cell Carcinoma.
  3. Diagnostic utility of dual 5-hydroxymethylcytosine/Melan-A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first-line test for the workup of sentinel lymph node specimen.
  4. Long-term clinical impact of sentinel lymph node biopsy in breast cancer and cutaneous melanoma.
  5. Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.
  6. Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma.
Association Between Facility Volume and Overall Survival - Dr. Richard Essner - Saint Johns Cancer Institute