Survival analysis in pediatric patients with rhabdomyosarcoma: 18-year experience at the National Cancer Institute - RJ

INTRODUÇÃO: Rabdomiossarcoma (RMS) representa o sarcoma de partes moles mais freqüente da infância, havendo poucas informações a seu respeito em países em desenvolvimento. OBJETIVOS: Estudar o perfil demográfico, social, clínico, biológico e patológico de pacientes portadores de rabdomiossarcoma tratados em uma instituição brasileira. Estimar a probabilidade acumulada de sobrevida global (SG) e de sobrevida livre de eventos (SLE) em 60 meses, assim como identificar fatores prognósticos. CASUÍSTICA E MÉTODOS: Foram analisados retrospectivamente 163 pacientes, no período de 1986 a 2004, que receberam tratamento multimodal seguindo orientações do protocolo Intergrupo para RMS III e IV. O estudo do percentual de positividade nuclear da miogenina foi realizado em 85 casos. RESULTADOS: As localizações da doença mais freqüentes foram cabeça e pescoço em 73 (44,7%), extremidade em 28 (17,2%), trato geniturinário em 25 (15,3%) e retroperitônio em 14 (8,6%) pacientes. O subtipo histológico foi embrionário em 99 (60,75%) pacientes e alveolar/sarcoma indiferenciado em 65 (38,7%). Foi observada positividade nuclear da imunoistoquímica com miogenina (> 75% das células) em 80% dos casos com RMS alveolar. O tamanho tumoral foi > 5 cm em 89%, com invasividade (T2) em 80,4% e comprometimento de linfonodos regionais em 45 (27,6%) pacientes. A maioria dos pacientes encontrava-se nos grupos clínicos III (49,1%) e IV (39,3%). O estado nutricional foi avaliado com o percentil do índice de massa corporal (IMC), sendo encontrado baixo peso ( 75%), was observed in 80% of alveolar RMS patients. Tumor size > 5 cm was seen in 89%, invasivity (T2) in 80.4% and regional lymph node involvement in 45 (27.6%) patients. Most patients were in clinical groups (CG) III (49.1%) and IV (39.3%). The BMI was below the 10th percentile in 49 (30%) patients. With a median follow-up of 32 months, estimated OS and EFS for the whole group were 48.6% and 42.2%, respectively. The EFS for patients in CG I + II, III and IV was 73.3%, 57.5% and 14.9%, respectively (p = 0.001). Univariate analysis showed that OS in 60 months was adversely influenced by age < 1 year and maior ou igual a 10 year, black skin, metastatic disease, one or two and more metastatic sites, extremity as primary site, lymph node N1 or NX, invasivity, and histological subtype alveolar. Multivariate analysis showed that independent prognostic factors for OS were age < 1 year (p = 0.022) and maior ou igual a 10 years (p = 0.069), one or two and more metastatic sites (p < 0.001), BMI percentile menor ou igual 10 (p = 0.027); independent prognostic factors for EFS were BMI < 10th percentile (p = 0.036) and the presence of regional lymph node N1 e NX (p < 0.001); for EFS in Summary non-metastatic patients, BMI < 10th percentile (p = 0.003) and the presence of regional lymph nodes N1 (p = 0.003) and NX (p = 0.002). Tumor size was one of the most important factors, although not selected for the multivariate model. The positivity of myogenin had no prognostic significance. CONCLUSIONS: The results of this study suggest that besides disease characteristics, nutritional and socio-economic factors should be considered in planning treatment and in the analysis of prognostic factors. Metastatic disease is associated with bad prognosis. All efforts should be taken to provide early diagnosis

Contribution of multiparameter flow cytometry immunophenotyping to the diagnostic screening and classification of pediatric cancer.

Pediatric cancer is a relatively rare and heterogeneous group of hematological and non-hematological malignancies which require multiple procedures for its diagnostic screening and classification. Until now, flow cytometry (FC) has not been systematically applied to the diagnostic work-up of such malignancies, particularly for solid tumors. Here we evaluated a FC panel of markers for the diagnostic screening of pediatric cancer and further classification of pediatric solid tumors. The proposed strategy aims at the differential diagnosis between tumoral vs. reactive samples, and hematological vs. non-hematological malignancies, and the subclassification of solid tumors. In total, 52 samples from 40 patients suspicious of containing tumor cells were analyzed by FC in parallel to conventional diagnostic procedures. The overall concordance rate between both approaches was of 96% (50/52 diagnostic samples), with 100% agreement for all reactive/inflammatory and non-infiltrated samples as well as for those corresponding to solid tumors (n = 35), with only two false negative cases diagnosed with Hodgkin lymphoma and anaplastic lymphoma, respectively. Moreover, clear discrimination between samples infiltrated by hematopoietic vs. non-hematopoietic tumor cells was systematically achieved. Distinct subtypes of solid tumors showed different protein expression profiles, allowing for the differential diagnosis of neuroblastoma (CD56(hi)/GD2(+)/CD81(hi)), primitive neuroectodermal tumors (CD271(hi)/CD99(+)), Wilms tumors (>1 cell population), rhabdomyosarcoma (nuMYOD1(+)/numyogenin(+)), carcinomas (CD45(-)/EpCAM(+)), germ cell tumors (CD56(+)/CD45(-)/NG2(+)/CD10(+)) and eventually also hemangiopericytomas (CD45(-)/CD34(+)). In summary, our results show that multiparameter FC provides fast and useful complementary data to routine histopathology for the diagnostic screening and classification of pediatric cancer

Immunophenotypic identification and chraracterization of pediatric tumor samples.

<p>In panel A, an illustrating example of the gating strategy and bivariate dot plot combinations used for the identification of CD45− tumor cells, CD45− residual stromal cells (e.g. endothelial cells and mesenquimal cells) and infiltrating hematopoietic cells (e.g. neutrophils, B and T cells) is shown. In turn, in panels B to J the immunophenotypic profile of CD45− tumor cells from a neuroblastoma (panels B and H), a PNET (panels C and I) and a rhabdomyossarcoma (panels D and J) tumor are shown together with representative pictures of the histophathological and immunohistochemical profiles of the same tumors stained with hematoxilin & eosin plus cromogranin (neuroblastoma cells in panel E), CD99 (PNET cells in panel F) and _(nu)myogenin (rhabdomyossarcoma cells in panel G).</p

Comparison between multiparameter flow cytometry (MFC) and histopathology plus immunohistochemistry (IH) as regards identification of infiltration by neoplastic cells versus normal/reactive cells.

<p>All 8 samples were obtained from pediatric cancer patients, but they were all negative for the presence of tumor cells by conventional diagnostic approaches. LL: lymphoblastic lymphoma; PNET- primitive neuroectodermal tumor.</p

Pattern of antigen expression by tumor cells from different diagnostic categories of pediatric solid tumors.

<p>−: negative; +lo :low expression levels/cells; +: positive; +hi: strong expression levels/cells.</p><p>Both CD7 and CD8 were systematically negative in all tumors analyzed.</p>*<p>The only ganglioneuroblastoma tumor analyzed showed a similar profile but it contained two distinct populations which differed on CD56, CD9 and CD81 expression, in the absence of CD117.</p> <p>CD271 was only partially present in one neuroblastoma tumor.</p>§<p>% of positive cells only among positive case.</p