ABSTRACT
Under current AJCC staging criteria, stage IIC patients paradoxically have worse outcomes than IIIA patients despite the lack of nodal metastatic disease. This study sought to identify additional clinicopathologic characteristics correlated with worse patient outcomes. Retrospective chart review of stage IIC and IIIA melanoma patients were evaluated between 1995 and 2011 with clinical follow-up through 2015. Records were reviewed for demographics, clinical characteristics, and tumor pathology. Fisher's exact test and Wilcoxon's rank-sum test were used to assess group differences. Clinicopathologic features were evaluated relative to overall survival (OS), time to distant metastases, and local/regional recurrence. Overall, 128 patients were included (45 stage IIC and 83 stage IIIA) with a median follow-up time of 5.7 years. Compared with stage IIIA patients, stage IIC patients were older, and their melanomas were more likely to be nodular, amelanotic, thicker, have higher mitotic rate, tumor lymphocytic infiltrate, no radial growth phase, and less likely to have associated precursor lesions. Stage IIC patients had shorter OS and time to distant metastases; multivariate regression revealed that older age (>55 years) and mitotic rate (>5 mitoses/mm) were independent predictors of OS. Melanomas in stage IIC disease may be biologically distinct from those that are seen in stage IIIA. While sentinel node biopsies remain the standard-of-care, these results suggest that clinicians may want to assess the clinicopathologic characteristics described above to aggressively counsel, screen for distant disease, and consider adjuvant therapy, in particular for older patients and higher mitotic rates in thicker primary tumors, regardless of nodal status.
Subject(s)
Melanoma/pathology , Neoplasm Recurrence, Local/pathology , Skin Neoplasms/secondary , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Melanoma/surgery , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Retrospective Studies , Skin Neoplasms/surgery , Survival Rate , Young AdultABSTRACT
BRAF inhibitors (BRAFi) have led to clinical benefit in patients with melanoma. The development of a blood-based assay to detect and quantify BRAF levels in these patients has diagnostic, prognostic, and predictive capabilities that could guide treatment decisions. Blood BRAF(V600E) detection and quantification were performed on samples from 128 patients with stage II (19), III (67), and IV (42) melanoma. Tissue BRAF analysis was performed in all patients with stage IV disease and in selected patients with stage II and III disease. Clinical outcomes were correlated to initial BRAF levels as well as BRAF level dynamics. Serial analysis was performed on 17 stage IV melanoma patients treated with BRAFi and compared with tumor measurements by RECIST. The assay was highly sensitive (96%) and specific (95%) in the stage IV setting, using a blood level of 4.8 pg as "positive." BRAF levels typically decreased following BRAFi. A subset of these patients (5) had an increase in BRAF(V600E) values 42 to 112 days before clinical or radiographic disease progression (PD). From 86 patients with resected, stage II or III melanoma, 39 had evidence of disease relapse (45.3%). Furthermore, BRAF mutation in the blood after surgical resection in these patients was not associated with a difference in relapse risk, although tissue BRAF status was only available for a subset of patients. In summary, we have developed a highly sensitive and specific, blood-based assay to detect BRAF(V600) mutation in patients with melanoma.
Subject(s)
DNA Mutational Analysis/methods , Melanoma/diagnosis , Melanoma/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Amino Acid Substitution , Cell Line, Tumor , Codon , DNA Mutational Analysis/standards , Genotype , Humans , Leukocytes, Mononuclear , Melanoma/drug therapy , Molecular Targeted Therapy , Neoplasm Staging , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
There is no general consensus regarding the optimal follow-up strategy for patients with melanoma. We sought to determine the utility and cost effectiveness of radiological restaging of patients with stage IIB-IIIC melanoma at the 3-year follow-up time point. A retrospective review of 210 patients diagnosed with stage IIB-IIIC melanoma seen in the Cutaneous Oncology Program at Beth Israel Deaconess Medical Center between January, 2001 and July, 2006 was conducted. Fifty-two patients were asymptomatic and continuously disease free and underwent restaging head computed tomography (CT) or MRI and torso CT scans 3 years after completion of local-regional therapy or initiation of adjuvant treatment. True positive, false positive and normal scans were identified and the cost per diagnosis calculated. Fifty-five percent of patients developed melanoma recurrences: 88% before 3 years (median time to recurrence 12 months, 95% confidence interval: 10-16 months). The majority of patients (69%) recurred with disease symptoms. Twenty-five head CT scans, 27 head MRIs, and 52 torso CTs were performed. One false-positive head CT and five abnormal torso CT scans (three false positive, two true positive) were identified. The total cost per diagnosis was $312,990. Extensive 3-year restaging imaging seems to be of limited value for symptomatic and continuously disease-free patients with stage IIB-IIIC melanoma. Furthermore, given the low risk of recurrence beyond 3 years, it is likely that subsequent routine imaging would have similarly low utility.
