Use of S-100B to Evaluate Therapy Effects during Bevacizumab Induction Treatment in AJCC Stage III Melanoma

To investigate the feasibility of using bevacizumab to improve the survival of American Joint Committee on Cancer (AJCC) stage III melanoma patients, we investigated how a single bevacizumab treatment affected nodal disease and a panel of biomarkers in clinically fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT)-staged, stage III melanoma patients, prior to therapeutic lymph node dissection (TLND). Four weeks before TLND, nine patients (median age 50, range 28.8-62.1 years; two male, seven female) with palpable lymph node metastases received 7.5 mg/kg bevacizumab. Before and after this treatment, all patients were assessed by measurements of the maximum standardized uptake value (SUVmax) by FDG-PET scan, and serum S-100B and lactate dehydrogenase (LDH). After TLND, the dissection specimen was analyzed for number of removed lymph nodes, number of metastatic lymph nodes, and tumor necrosis. Median follow-up was 15.5 (2.2-32.9) months. Histopathological analysis revealed tumor necrosis in six patients, of whom five had an S-100B decline and one had an unchanged S-100B level after bevacizumab. The other three patients showed an S-100B increase and no necrosis. Tumor necrosis was correlated with S-100B decrease (P = 0.048). No association was found between necrosis and the markers SUVmax and LDH. No wound healing disturbances were encountered. Tumor necrosis in dissection specimens was associated with declining S-100B levels, while elevated S-100B was only found in cases with no necrosis. Bevacizumab might be useful in treating AJCC stage III melanoma patients prior to TLND, and S100-B appears to be a useful marker for assessment of treatment effects

S-100B Concentrations Predict Disease-Free Survival in Stage III Melanoma Patients

Elevation of the tumor marker S-100B in melanoma patients is a highly specific indicator of recurrence. The role of S-100B in disease-free survival (DFS) was evaluated in stage III melanoma patients (staged with fluorodeoxyglucose positron emission tomography [FDG-PET] and computed tomography [CT]) with palpable lymph node metastases who underwent therapeutic lymph node dissection. S-100B and LDH were measured on the day before surgery (d = -1) and on days 1, 2, and 7 postoperatively. Multivariate logistic regression was used to study factors associated with preoperative elevation of S-100B. Univariate (log-rank test) and multivariate (Cox regression) survival analyses were performed to identify factors associated with DFS. Between 2004 and 2008, 56 patients (median age 57, range 24-93) years, 27 males (48%) and 29 females (52%) entered the study. Preoperative S-100B elevation was found in 27 patients (48%) and elevated LDH in 20 patients (36%). No association was found between these two markers at any time. Multivariate analysis showed that elevated S-100B preoperatively (hazard ratio [HR] 2.7, P = .03) was associated with DFS. S-100B elevation was associated with increased tumor size (odds ratio [OR] 3.40; P = .03). Elevated S-100B preoperatively in patients with optimally staged clinical stage III melanoma is associated with decreased disease-free survival. S100-B could be used as a prognostic marker in the stratification of new adjuvant trials to select stage III melanoma patients for adjuvant systematic treatment

S-100B:A Stronger Prognostic Biomarker than LDH in Stage IIIB-C Melanoma

<p>In melanoma patients with nodal macrometastases, the distinction between good and poor prognosis is based on the presence of primary melanoma ulceration or metastatic involvement of 4 or more lymph nodes in the 7th edition of the American Joint Committee on Cancer (AJCC) classification. We hypothesized that biomarkers would increase the accurateness of staging in these patients. The aim was to assess and compare the prognostic impact of biomarkers S-100B and LDH and to determine the best timing of their measurement in stage IIIB-C melanoma.</p><p>A total of 119 patients underwent therapeutic lymph node dissection (TLND) for nodal macrometastases with serum S-100B and LDH level measurements preoperatively. In 75 of them, S-100B and LDH were also measured on postoperative days 1 and 2. S-100B and LDH levels on days 0, 1, and 2 were compared for their association with disease-free survival (DFS) and disease-specific survival (DSS).</p><p>At a median follow-up of 17 (range 1-89) months, S-100B levels at all time points were associated with DFS. In multivariable analysis, preoperative S-100B and S-100B measured on day 2 showed the strongest association with DFS (hazard ratio [HR] 2.55, P = 0.007 and HR 3.80, P = 0.01). For DSS, the preoperative S-100B level was the strongest independent predictor (HR 2.81, P = 0.01). LDH measurements showed a significant association with DSS in univariate analysis only when measured preoperatively (HR 2.46, P = 0.01). In multivariable analysis, LDH measurement was not associated with melanoma prognosis.</p><p>The S-100B level measured preoperatively is, in contrast to LDH, one of the most important independent predictors of melanoma prognosis in patients undergoing TLND for nodal macrometastases.</p>

Tumour assessment in advanced melanoma: value of FDG-PET/CT in patients with elevated serum S-100B

PURPOSE: To evaluate the usefulness of PET/CT in melanoma patients with an elevated serum S-100B tumour marker level. METHODS: Out of 165 consecutive high-risk melanoma patients referred for PET/CT imaging, 47 had elevated (>0.2 microg/l) S-100B serum levels and a contemporaneous 18F-FDG PET/CT scan. PET/CT scans were evaluated for the presence of metastases. To produce a composite reference standard, we used cytological, histological, MRI and PET/CT follow-up findings as well as clinical and S-100B follow-up. RESULTS: Among the 47 patients with increased S-100B levels, PET/CT correctly identified metastases in 38 (30 distant metastases and eight lymph node metastases). In one patient with cervical lymph node metastases, PET/CT was negative. Eight patients had no metastases and PET/CT correctly excluded metastases in all of them. Overall sensitivity for metastases was 97% (38/39), specificity 100% (8/8) and accuracy 98% (46/47). S-100B was significantly higher in patients with distant metastases (mean 1.93 microg/l, range 0.3-14.3 microg/l) than in patients with lymph node metastases (mean 0.49 microg/l, range 0.3-1.6 microg/l, p=0.003) or patients without metastases (mean 0.625 microg/l, range 0.3-2.6 microg/l, p=0.007). However, 6 of 14 patients with a tumour marker level of 0.3 microg/l had no metastases. CONCLUSION: In melanoma patients with elevated S-100B tumour marker levels, FDG-PET/CT accurately identifies lymph node or distant metastases and reliably excludes metastases. Because of the significant number of false positive S-100B tumour marker determinations (17%), we recommend repetition of tumour marker measurements if elevated S-100B levels occur before extensive imaging is used