A simple cost-effective lactate dehydrogenase level measurement can stratify patients with Ewing’s tumor into low and high risk
Authors: C.M.L. da Costa, A. Lopes, B. de Camargo
Journal: Annals of Oncology (2003)

Identification of prognostic factors is essential in the treatment of cancer to distinguish low- and high-risk patients, thereby allowing stratification of patients for standard or intensified treatment protocols. Pretreatment levels of serum lactate dehydrogenase (LDH) might be a useful marker to identify different risk levels in Ewing’s sarcoma [1.Bacci G. Ferrari S. Longhi A. et al.Prognostic significance of serum LDH in Ewing’s sarcoma of bone.Oncol Rep. 1999; 6: 807-811PubMed Google Scholar]. We reviewed the experience of a single institution over 12 years to document overall survival and prognostic factors. This was based on the records of 105 children and adolescents with Ewing’s tumor of the bone treated from June 1984 to 1996. There were 54 males and 51 females. Ages ranged from 1 to 18 years (mean 10 years; median 11 years). The most common primary tumor sites were the pelvis (25 cases) and femur (24 cases). Fifty-seven had extremity lesions and 48 axial. Thirty-four presented with detectable metastases. Serum LDH was measured at diagnosis in 72 patients, giving a mean of 370 U/l; 23% had LDH >370 U/l. Measurements of LDH were divided into two groups: below the mean value (<370 U/l) and above or equal to the mean (≥370 U/l). The chemotherapy schedules were not uniform. Local therapy was individualized. Surgery was used whenever possible and radiotherapy was combined with surgery when surgical margins were positive or histological response (Huvos grade [2.Huvos A.G. Bone Tumors: Diagnosis Treatment and Prognosis.2nd edition. WB Saunders, Philadelphia PA2019Google Scholar]) was poor (grade I/II). Combined therapy was administered in 93 patients: 53 chemotherapy plus surgery; 19 chemotherapy plus radiotherapy; and 21 chemotherapy, radiotherapy and surgery. Twelve patients received only chemotherapy. The grade of necrosis in the primary tumor was evaluated in 52 cases, and 35 had grade III or IV histological responses. Overall survival for the whole group was 50% after 5-year follow-up. Univariate analysis showed the following prognostic factors: raised LDH [hazard ratio (HR) 4.40, 95% confidence interval (CI) 2.25–8.62, P <0.0001]; no clinical response to chemotherapy (HR 8.40, 95% CI 0.04–0.15, P <0.0001); tumor necrosis (HUVOS grade I/II) (HR 1.65, 95% CI 0.09–0.58, P = 0.008); and metastases (HR 1.20, 95% CI 1.15–3.45, P = 0.014). Cox multiple regression analysis showed that raised serum LDH levels (HR 2.20, 95% CI 1.43–6.26, P = 0.003)and no clinical response to chemotherapy (HR 11.30, 95% CI 4.87–26.22, P <0.0001) were independent prognostic factors. The 5-year survival rate of 50% in our institution is comparable with many other studies. Descriptions of prognostic factors in the literature have suggested that the most important are the presence of distant metastases at diagnosis, axial primary site, older patient age and larger tumor size [3.Ahrens S. Hoffmann C. Jabar S. et al.Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing Sarcoma Study.Med Pediatr Oncol. 1999; 32: 186-195Crossref PubMed Scopus (97) Google Scholar, 4.Picci P. Bohling T. Bacci G. et al.Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing’s sarcoma of the extremities.J Clin Oncol. 1997; 15: 1553-1559Crossref PubMed Scopus (201) Google Scholar, 5.Wunder J.S. Paulian G. Huvos A.G. et al.The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma.J Bone Joint Surg Am. 1998; 80: 1020-1033Crossref PubMed Scopus (3) Google Scholar, 6.Cotterill S.J. Ahrens S. Paulussen M. et al.Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group.J Clin Oncol. 2000; 18: 3108-3114Crossref PubMed Scopus (762) Google Scholar]. In our series the most powerful prognostic factor to predict death and survival was the pretreatment serum LDH level. Clinical response to chemotherapy has been shown to be strongly correlated with outcome [4.Picci P. Bohling T. Bacci G. et al.Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing’s sarcoma of the extremities.J Clin Oncol. 1997; 15: 1553-1559Crossref PubMed Scopus (201) Google Scholar]. Histological response, using the Huvos classification, was a prognostic factor but not independent. Our data suggest that pretreatment LDH level is a simple cost-effective prognostic factor that can be considered as a criterium to treat patients in different groups.