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Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy.

Weide B, Richter S, Büttner P, Leiter U, Forschner A, Bauer J, Held L, Eigentler TK, Meier F, Garbe C - PLoS ONE (2013)

Bottom Line: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral), the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy) were associated with overall survival (all p<0.001).In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001), S100B (HR 1.6 [1.2-2.1]; p<0.001) and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009), but not the type of treatment had significant independent impact.Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany ; German Cancer Research Center (DKFZ), Heidelberg, Germany ; German Cancer Consortium (DKTK), Heidelberg, Germany.

ABSTRACT

Background: Prognostic factors of melanoma with distant metastasis and systemic treatment are only poorly established. This study aimed to analyse the impact of S100B, lactate dehydrogenase (LDH) and the type of treatment on survival in advanced patients receiving systemic treatment.

Patients and methods: We analysed overall survival of 499 patients from the university department of dermatology in Tuebingen, Germany, with unresectable melanoma at the time point of initiation of first-line systemic therapy. Only patients who started treatment between the years 2000 and 2010 were included. Disease-specific survival was calculated by bivariate Kaplan Meier survival probabilities and multivariate Cox hazard regression analysis.

Results: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral), the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy) were associated with overall survival (all p<0.001). In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001), S100B (HR 1.6 [1.2-2.1]; p<0.001) and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009), but not the type of treatment had significant independent impact. Among those factors normal S100B was the best indicator of long-term survival, which was 12.3% after 5 years for this subgroup.

Conclusion: Serum S100B is a prognostic marker predicting survival at the time of initiation of first-line treatment in unresectable melanoma patients. Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

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Univariate analysis of 499 patients.Kaplan Meier survival curves according to (A) the site of distant metastasis, (B) the presence of brain metastases, (C) the LDH serum level, (D) the S100B serum level, (E) the type of treatment, and (F) the number of applicable unfavourable independent prognostic factors according to the multivariate analysis (S100B, LDH, presence of brain metastasis). Censored events are indicated by vertical lines.
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pone-0081624-g001: Univariate analysis of 499 patients.Kaplan Meier survival curves according to (A) the site of distant metastasis, (B) the presence of brain metastases, (C) the LDH serum level, (D) the S100B serum level, (E) the type of treatment, and (F) the number of applicable unfavourable independent prognostic factors according to the multivariate analysis (S100B, LDH, presence of brain metastasis). Censored events are indicated by vertical lines.

Mentions: Both factors considered in the AJCC-staging system for patients with distant metastasis (site of distant metastases and LDH) were strongly correlated with survival before receiving the first systemic therapy. If distant lesions were limited to soft tissue or the lung MST was 13 or 12 months, respectively, while it was shorter for patients with other visceral lesions (8 months; p<0.001; Figure 1A). The probability to be alive one year after start of systemic treatment was twice as high for patients without cerebral involvement compared to those with brain metastasis (44.9 vs. 22.5; log rank p<0.001; Figure 1B). Both analysed serum markers were significantly (each log rank p<0.001) associated with survival (Figure 1C, 1D). In patients with an elevated LDH levels MST was 5 months, representing the most powerful indicator for poor MST among all analysed factors. Differences in prognosis were likewise observed according to the type of treatment, with poorest MST of 6 months in patients receiving polychemotherapy and favourable MST of 12 months for those treated with biochemotherapy. Immunotherapy was associated with a MST of 9 months but the chance for long term benefit was highest for those patients with a probability of 15.6% to survive 5 years or longer (Figure 1E). No differences in prognosis were evident for age, gender, or histopathological characteristics of the primary melanoma. An overview over one- and two-year survival rates is presented in Table 1.


Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy.

Weide B, Richter S, Büttner P, Leiter U, Forschner A, Bauer J, Held L, Eigentler TK, Meier F, Garbe C - PLoS ONE (2013)

Univariate analysis of 499 patients.Kaplan Meier survival curves according to (A) the site of distant metastasis, (B) the presence of brain metastases, (C) the LDH serum level, (D) the S100B serum level, (E) the type of treatment, and (F) the number of applicable unfavourable independent prognostic factors according to the multivariate analysis (S100B, LDH, presence of brain metastasis). Censored events are indicated by vertical lines.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842933&req=5

pone-0081624-g001: Univariate analysis of 499 patients.Kaplan Meier survival curves according to (A) the site of distant metastasis, (B) the presence of brain metastases, (C) the LDH serum level, (D) the S100B serum level, (E) the type of treatment, and (F) the number of applicable unfavourable independent prognostic factors according to the multivariate analysis (S100B, LDH, presence of brain metastasis). Censored events are indicated by vertical lines.
Mentions: Both factors considered in the AJCC-staging system for patients with distant metastasis (site of distant metastases and LDH) were strongly correlated with survival before receiving the first systemic therapy. If distant lesions were limited to soft tissue or the lung MST was 13 or 12 months, respectively, while it was shorter for patients with other visceral lesions (8 months; p<0.001; Figure 1A). The probability to be alive one year after start of systemic treatment was twice as high for patients without cerebral involvement compared to those with brain metastasis (44.9 vs. 22.5; log rank p<0.001; Figure 1B). Both analysed serum markers were significantly (each log rank p<0.001) associated with survival (Figure 1C, 1D). In patients with an elevated LDH levels MST was 5 months, representing the most powerful indicator for poor MST among all analysed factors. Differences in prognosis were likewise observed according to the type of treatment, with poorest MST of 6 months in patients receiving polychemotherapy and favourable MST of 12 months for those treated with biochemotherapy. Immunotherapy was associated with a MST of 9 months but the chance for long term benefit was highest for those patients with a probability of 15.6% to survive 5 years or longer (Figure 1E). No differences in prognosis were evident for age, gender, or histopathological characteristics of the primary melanoma. An overview over one- and two-year survival rates is presented in Table 1.

Bottom Line: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral), the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy) were associated with overall survival (all p<0.001).In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001), S100B (HR 1.6 [1.2-2.1]; p<0.001) and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009), but not the type of treatment had significant independent impact.Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany ; German Cancer Research Center (DKFZ), Heidelberg, Germany ; German Cancer Consortium (DKTK), Heidelberg, Germany.

ABSTRACT

Background: Prognostic factors of melanoma with distant metastasis and systemic treatment are only poorly established. This study aimed to analyse the impact of S100B, lactate dehydrogenase (LDH) and the type of treatment on survival in advanced patients receiving systemic treatment.

Patients and methods: We analysed overall survival of 499 patients from the university department of dermatology in Tuebingen, Germany, with unresectable melanoma at the time point of initiation of first-line systemic therapy. Only patients who started treatment between the years 2000 and 2010 were included. Disease-specific survival was calculated by bivariate Kaplan Meier survival probabilities and multivariate Cox hazard regression analysis.

Results: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral), the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy) were associated with overall survival (all p<0.001). In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001), S100B (HR 1.6 [1.2-2.1]; p<0.001) and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009), but not the type of treatment had significant independent impact. Among those factors normal S100B was the best indicator of long-term survival, which was 12.3% after 5 years for this subgroup.

Conclusion: Serum S100B is a prognostic marker predicting survival at the time of initiation of first-line treatment in unresectable melanoma patients. Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

Show MeSH
Related in: MedlinePlus