Prospective Evaluation of Hypoxia in Primary Melanoma
Yana Najjar
Summary
When controlling for tumor present in the Sentinel lymph node (SLN), intranodal hypoxia, as measured by Carbonic Anhydrase IX (CAIX IHC), is associated with worse PFS. This suggests that melanoma tumors may be utilizing deregulated metabolism as a means of propagating themselves to the next station of metastasis. This study aims to prospectively validate previous findings. Patients who are to undergo WLE and SLNB per standard of care (SOC) will be evaluable. It is hypothesized that SLN(s) with increased hypoxia, as measured by pimonidazole staining, will be associated with worse Progression-free Survival (PFS).
Description
This study aims to prospectively validate previous findings. Having found that deregulated tumor cell metabolism and resultant intra-tumoral hypoxia (ITH) are linked to clinical outcomes in patients with advanced stage melanoma, it was next sought to understand whether hypoxia, utilized as a surrogate of dysregulated metabolism, has significance in patients with earlier stage melanoma. This was done by utilizing banked samples from melanoma patients. Patients with early-stage melanoma who had undergone wide local excision (WLE) and sentinel lymph node biopsy (SLNB) were eligible, involving fif…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Must be willing and able to provide written informed consent for the study. 2. Must have histologically confirmed melanoma for which a Sentinel Lymph Node Biopsy (SLNB) is indicated per the treating physician. 3. Cutaneous or mucosal melanoma is permitted. 4. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 7 days from the time of pimonidazole administration. 1. Female subjects of childbearing potential must not be pregnant or breastfeeding. Female subjects will be considered of non-reproductive potential if they:…
Interventions
- DrugPimonidazole
Drug: Pimonidazole Pimonidazole is not used with therapeutic intent, and has a non-hazardous designation. It has been widely used for in vivo evaluation of intratumor hypoxia, and patients will take PO pimonidazole before the scheduled biopsy. Patients receive an oral dose of pimonidazole, a safe chemical tracer up to 24 hours prior to biopsy. Pimonidazole allows for true hypoxia staining; pimonidazole binds hypoxic proteins covalently, creating an antigen that facilitates the imaging, flow cytometry, and scRNA-seq experiments proposed. Pimonidazole has been previously used in patients and is safe and well tolerated, without anticipated adverse events.
Location
- UPMC Hillman Cancer CenterPittsburgh, Pennsylvania