Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

Abstract

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1 -2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6 -97) and 98.9% (95% CI: 97.7 -100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2 -89.5; OS 93.2%, 95% CI: 88.7 -97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Influence of image‐defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group

“…Furthermore, treatment itself poses a threat for the child. In LNESG1 only one of three deaths in patients with INSS stage 1 disease was due to tumour progression, the other two were related to treatment [6]. Today we believe that a substantial number of our patients would have survived if they had been followed with observation only [13,14].…”

“…INSS stage, tumour site, progression/relapses and deaths were recorded. OC, biochemical, histological and biological analyses were as previously described [5,6].…”

“…Since then survival in LNESG1 related to INSS have been reported [6]. In 2005 the International Neuroblastoma Risk Group (INRG) Task Force, representing all major co-operative paediatric cancer groups, adopted the principle of surgical risk factors and incorporated it in the INRG Staging System [7,8].…”

Overview and recent advances in the treatment of neuroblastoma

“…The COG P9641 study demonstrated excellent OS for these patients with surgical resection alone, with a 5-year OS rate of 99% for those with INSS stage 1 and 96% for patients with asymptomatic INSS 2A or 2B tumors [52]. The European International Society of Pediatric Oncology Neuroblastoma Group trial LNESG1 also demonstrated that surgical resection alone is curative in the vast majority of patients with localized disease, with an OS rate of 99% for stage 1 patients and 93% for stage 2 patients [55].…”

“…The INRG classification system was developed based on analysis of 13 clinical and biological variables for effects on event-free survival rates, including patient age at diagnosis, INRGSS tumor stage, serum lactate dehydrogenase and ferritin levels, tumor histological category, grade of differentiation, tumor [51,52] (Figure 3). For those patients with localized, resectable disease, surgical resection alone is generally curative, and chemotherapy is effective salvage for those with relapses after resection [53][54][55]. Low-stage tumors with favorable biological features often do not metastasize even after incomplete resection, and therefore, for these patients, chemotherapy is reserved for those with life or organ-threatening symptoms, such as spinal cord compression or respiratory compromise.…”