Metastatic neuroblastoma: Factors influencing survival

Abstract

Ninety of 142 patients (63%) with neuroblastoma had metastatic disease at the time of diagnosis. Seventy-four (52%) patients had stage IV disease and 16 (11%) had stage IV-S. Survival in stage IV-S was 75% (12/16). Four deaths occurred in infants under 6 wk of age, three of whom had bone marrow involvement. Deaths were related to respiratory insufficiency and sepsis rather than progression of disease. All patients over 6 wk of age survived with resection of primary tumor and skin metastases. Survivors had slow, spontaneous regression of tumor over a 6–15 mo period regardless of treatment. Bone marrow involvement with tumor reduces the otherwise favorable outlook for patients with stage IV-S disease. This suggests that patients with bone marrow metastases be excluded from stage IV-S classification. Of 74 patients with stage IV disease, 49 were boys and 25 were girls, with a mean age of 37 mo. Site of primary tumor was adrenal in 40 patients, paraspinal in 27, and mediastinal in seven. Prior to 1965, the mean survival was 3 mo. Since that time, with chemotherapy programs, the mean survival is 20 mo with 18% of patients surviving more than 2 yr. While there is little objective evidence that chemotherapy increases the cure rate, it can reduce tumor size, cause histologic maturation of tumor, and result in considerable palliation. There are six survivors (8%) disease-free longer than 2 yr. Two were under 13 mo of age and three over 6 yr. All had delayed primary or second-look tumor resections, and five had bone marrow involvement, but only two had bone cortex metastases. These observations suggest that resection of bulk tumor and histologic evidence of tumor maturation, particularly in patients with only bone marrow involvement, may result in an occasional survival. These data further suggest a modification in the staging of metastatic cases into three groups: stage IV-M, bone marrow involvement only; stage IV-B, metastatic disease including bone cortex; and stage IV-S, metastatic disease involving liver and skin only. Ninety of 142 patients (63%) with neuroblastoma had metastatic disease at the time of diagnosis. Seventy-four (52%) patients had stage IV disease and 16 (11%) had stage IV-S. Survival in stage IV-S was 75% (12/16). Four deaths occurred in infants under 6 wk of age, three of whom had bone marrow involvement. Deaths were related to respiratory insufficiency and sepsis rather than progression of disease. All patients over 6 wk of age survived with resection of primary tumor and skin metastases. Survivors had slow, spontaneous regression of tumor over a 6–15 mo period regardless of treatment. Bone marrow involvement with tumor reduces the otherwise favorable outlook for patients with stage IV-S disease. This suggests that patients with bone marrow metastases be excluded from stage IV-S classification. Of 74 patients with stage IV disease, 49 were boys and 25 were girls, with a mean age of 37 mo. Site of primary tumor was adrenal in 40 patients, paraspinal in 27, and mediastinal in seven. Prior to 1965, the mean survival was 3 mo. Since that time, with chemotherapy programs, the mean survival is 20 mo with 18% of patients surviving more than 2 yr. While there is little objective evidence that chemotherapy increases the cure rate, it can reduce tumor size, cause histologic maturation of tumor, and result in considerable palliation. There are six survivors (8%) disease-free longer than 2 yr. Two were under 13 mo of age and three over 6 yr. All had delayed primary or second-look tumor resections, and five had bone marrow involvement, but only two had bone cortex metastases. These observations suggest that resection of bulk tumor and histologic evidence of tumor maturation, particularly in patients with only bone marrow involvement, may result in an occasional survival. These data further suggest a modification in the staging of metastatic cases into three groups: stage IV-M, bone marrow involvement only; stage IV-B, metastatic disease including bone cortex; and stage IV-S, metastatic disease involving liver and skin only.