Melanoma and Cutaneous Oncology

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

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, like blood and due to their roles in various cellular processes can be used for diagnosis and prognosis Our goal was to identity miRNAs present in the serum at the time of diagnosis that can predict early recurrence/development of metastases. This has not been studied in melanoma. We were able to identify 9 miRNAs that can predict which patient will recur within 2 years post-surgery. These preliminary data showed that we can determine which patient will develop metastases with more than 95% accuracy. We are currently working of confirming the results.

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 can diminish up to only 20-25%. Thus, there is a need to identify early patients who will develop metastases. This will help clinicians to adapt more accurately the follow-up schedule and provide early access to systemic therapy to high-risk patients. Working with primary tumor samples collected during wide excision surgery, from melanoma patients who were followed for several years, we have recently identified 4 immune-modulating genes as predictors of metastases. These preliminary data showed that these 4 genes are predictive 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

Understanding the immune landscape in melanoma patients’ metastases in advanced stage melanoma patients.

Surgical resection of metastases in melanoma patients has historically played a prominent role in
treatment. Advances in systemic therapy have altered the therapeutic landscape. Previous studies have demonstrated that metastasectomy should continue to be considered for selected patients with stage III/IV melanoma. We want to identify which patients will benefit from surgery by studying the immune cell infiltrate of their resected metastases. We are focusing on patients with i) lung, ii) gastrointestinal track or, iii) lymph nodes metastases. Using techniques that evaluate gene activity of the tumor and immune cells while keeping their location in the tissue, we are identifying genes specific to patient’s post-surgical outcomes.

Guidelines directed surgical care in primary melanoma.

In 2023, the Commission on Cancer (CoC) mandated evidence-based guidelines for surgical margin size and depth of the wide excision (WE) for cutaneous melanoma. We investigated the compliance of these guidelines in our large US western states health care system. Our goals are, first to assess how the guidelines were respected in 2022 (= before the 2023 CoC guidelines), second to evaluate how physicians comply to these guidelines in 2023 and finally to determine if and how these new guidelines improve the surgical management of primary melanoma.

Future Projects

Lymphoscintigraphy imaging to predict SLN status

Before SLNB procedure, patients undergo lymphoscintigraphy, a non-invasive technique that uses a radioactive tracer to map the lymphatic system. We believe that using artificial intelligence and machine learning on lymphoscintigraphy images we could predict the metastatic status of the SLN based on imaging.

Melanoma in situ

Melanoma in situ is localized only to the superficial layer of the skin, and present almost no risk of metastasis. Although rare, melanoma in situ can metastasize after wide excision of the primary tumor. We intend to develop tools to distinguish melanoma in situ that will become invasive to those that will not. We are planning to study the immune landscape of the primary in situ melanoma and to assess if it correlates to the patient’s outcome.

Skin Cancers in transplant patients

To better understand the natural history of and the clinical outcomes of the skin cancers (squamous cell, basal cell, melanoma or others) that develop prior to or after solid organ transplants and try to model which patients are at risk for developing these skin tumors and who is at risk for poor outcomes (graft loss or death from malignancy) based on patient and graft characteristics and immunosuppression approaches.

Manuscripts in Development

1.Guidelines directed surgical care in primary melanoma: Variability in an integrated health network

Summary: The National Comprehensive Cancer Network (NCCN) creates guidelines for the excision of primary cutaneous melanoma that surgeons should follow and record: 1) procedure intent, 2) Breslow thickness of the primary tumor, 3) surgical margins width and 4) depth of the wide excision (WE). Additionally, the NCCN recommends sentinel lymph node biopsy (SLNB) for patients with high-risk T1a and all others thicker melanoma. The objective of this study was to investigate the compliance with the surgical management guidelines in our 51 hospital western US integrated health care system in 2022.

2. Defining the Sentinel Lymph Node in Melanoma: Is the Hottest Node Always the Node with Metastasis?

Summary: Currently, sentinel lymph node biopsy (SLNB) is the widely accepted staging and prognostic procedure that determine SLN status. It relies on the use of a dye and/or a radiotracer to identify in which lymph node basin the tumor drains into. The lymph node that accumulates the most radiotracer is commonly referred to as the “hottest” node. The “hottest” node is removed by surgeons to determine whether the tumor has spread into it or not. Sometimes the dye/radiotracer also makes its way into other lymph nodes. The question then is whether this/these lymph nodes should be removed. Commonly, surgeons remove all nodes with counts of at least 10% of the hottest node. This study aims to determine if the hottest node reliably indicates the presence of metastases, and to establish the optimal level of radiotracer counts needed to identify a +SLN.

3. Completion Lymph Node Dissection Improves Survival in Intermediate Sentinel Lymph Node Metastasis: A Causal Inference Study on MSLT-II Data

Summary: The role of immediate completion lymph node dissection (iCLND) in melanoma patients with sentinel lymph node metastasis remains controversial. Prior studies suggest that the benefit of iCLND may depend on the size of the sentinel lymph node metastasis. We conducted a causal inference analysis to identify a subgroup of patients who would likely benefit from iCLND. Using causal inference techniques, including a random forest approach, we aimed to determine which group of patients with sentinel lymph node metastasis would most benefit from iCLND.