This phase II trial compares the effect of using risk-based stratification to guide surgical management to the usual approach in treating cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors that have not spread to other parts of the body (localized). Melanoma is a cancer that in children is sometimes difficult to tell apart from benign (not harmful) or atypical (uncertain if harmful) skin lesions. Failure to diagnose melanoma can result in inadequate surgical removal and increase the risk of recurrence and metastatic disease (spread from where it first started to other places in the body). In addition, diagnosing a tumor a benign (not cancer) tumor as cancer may lead to unnecessary surgery and treatment. This trial reviews tumor pathology and genetic markers and classifies the tumor as not atypical, atypical but low risk for spread and/or recurrence (coming back after a period of improvement), and atypical and high risk for spread and/or recurrence. The classifications are then used to provide surgical recommendations. Tumors that are not atypical do not receive any surgical treatment. Low-risk recommendations include removing a small layer of normal skin around the tumor. High-risk recommendations include the usual adult melanoma approach of removing a larger layer of normal skin around the tumor with or without a biopsy of the sentinel lymph node (the first lymph node to which tumor cells are likely to spread from a primary tumor). Risk-based guided surgical management may help avoid unnecessary surgery while improving outcomes in younger patients with localized cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors.
Patients ≤ 25 years old
Newly diagnosed localized cutaneous melanoma, atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasm by local institution pathology report
Patients must have disease that is localized to the skin on clinical assessment. Note that staging imaging is not required for the determination of eligibility, but if obtained prior to enrollment, all imaging must be consistent with localized cutaneous disease
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
Patients ≥ 18 years old with conventional adult-type melanoma are excluded. Note that patients 18-25 years old with atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasms are eligible
Patients with clinical evidence of metastatic disease such as palpable malignant adenopathy or symptomatic distant metastases are not eligible
Patients who have undergone re-excision to achieve a negative margin or sentinel lymph node biopsy for the melanocytic neoplasm under study are not eligible. Note that this does not exclude patients who have undergone the permitted diagnostic biopsy/excision, including re-biopsy, of the lesion
Any of the following diagnoses
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Chest Radiography
Procedure/SurgeryUndergo chest x-ray
Computed Tomography
Procedure/SurgeryUndergo CT or FDG PET/CT
Fludeoxyglucose F-18
Other interventionGiven FDG
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI, PET/MRI or brain MRI
Patient Observation
Other interventionUndergo observation
Positron Emission Tomography
Procedure/SurgeryUndergo whole body FDG PET/CT or PET/MRI
Re-Excision
Procedure/SurgeryUndergo narrow margin re-excision
Sentinel Lymph Node Biopsy
Procedure/SurgeryUndergo SLNB
Ultrasound Imaging
Procedure/SurgeryUndergo nodal basin ultrasound
Wide Local Excision
Procedure/SurgeryUndergo wide local excision
Feasibility success rate
Will be defined as the proportion of patients for whom risk stratification can be returned to the treating institution based on pathology and molecular data obtained through rapid central review.
Adherence to surgical treatment arm assignment
Will be defined as the proportion of patients who receive the specific protocol-assigned surgical management.
Incidence of grade 3-5 surgical adverse events
Will be defined according to the Clavien-Dindo Classification. Will be summarized descriptively by study arm.
Progression-free survival (PFS)
PFS is defined as time from date of enrollment to the earliest occurrence of relapse, disease progression/recurrence, SMN, or death due to any cause. The 2-year PFS along with the confidence intervals will be estimated using the Kaplan-Meier survival curves for each study arm separately: observation arm, low-risk arm A, and high-risk arm B.
Overall survival (OS)
OS is the time from date of enrollment to date of death due to any reason. The 2-year OS along with the confidence intervals will be estimated using the Kaplan-Meier survival curves for each study arm separately: observation arm, low-risk arm A, and high-risk arm B.
Surgical reconstruction techniques for pediatric patients with atypical and malignant melanocytic tumors
The analysis will consist of a descriptive summary of the surgical reconstruction techniques utilized in this cohort. Reconstruction techniques will be categorized as follows: primary closure; delayed primary closure; closure by secondary intention; autologous skin graft; skin graft, other material; local tissue flap; free flap with microvascular reconstruction; amputation; other. Frequencies and percentages will be reported for each technique.
The proportion of patients who undergo sentinel lymph node biopsy (SLNB) among the eligible high-risk arm B patients
The proportion will be summarized. Among patients with a positive SLNB, the rate of subsequent completion nodal dissection versus observation will be reported. The number of sentinel nodes sampled, size of largest metastatic nodal deposit, location of draining lymph node basin(s), number of lymph nodes resected at completion dissection will be summarized using appropriate descriptive statistics.
Surgical complications of completion nodal dissection
The occurrence of surgical complications including wound dehiscence, seroma or hematoma, hemorrhage, infection, skin graft failure, necrosis of flap used for reconstruction, lymphocele, lymphedema, and deep vein thrombosis will be summarized descriptively. The incidence of each complication will be calculated, accompanied by 95% confidence intervals if there are sufficient patients.
Concordance between local treating center pathologic diagnosis and central pathology review diagnosis
Will be assessed by comparing both the initial local treating center enrolling pathologic diagnosis (without incorporating molecular testing data) with the final central pathology review diagnosis, and final local diagnosis (with available molecular data incorporation) with the final central pathology review diagnosis. Concordance will be defined as agreement between the local and central reviewer on the assigned diagnostic category. Concordance rates will be reported as proportions with corresponding confidence intervals. For discordant cases, additional descriptive analysis may explore the nature and direction of the discrepancies.
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