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.

The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning.

Monclair T ，Mosseri V ，Cecchetto G ，De Bernardi B ，Michon J ，Holmes K ... -  《-》

Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection.

Patients with neuroblastoma are now stratified at diagnosis according to the presence and number of image-defined risk factors (IDRFs). We examined the added value of IDRF assessment after neoadjuvant chemotherapy for predicting surgical resection. From 2009-2012, 39 out of 91 patients operated on in our institution for neuroblastic tumors received neoadjuvant chemotherapy based on ongoing SIOPEN protocols or treatment guidelines. IDRFs were assessed both at diagnosis and preoperatively on CT and/or MRI. Median age at diagnosis was 30 months [range 2-191]. The tumor locations were adrenal (n = 20), paravertebral (n = 13) and perivascular (n = 6). INRGSS stages were L2 (n = 13), M (n = 25) and Ms (n = 1). Eleven tumors (28%) were MYCN-amplified. Chemotherapy reduced the number of IDRFs in 54% of patients overall (21/39): 61.5% (16/26) of M and Ms patients, and 38.5% (5/13) of non metastatic patients (P < 0.001). The number of IDRFs lost after chemotherapy was proportional to the degree of tumor shrinkage (P = 0.002), independent of the primary tumor location (P = 0.73), although the number was higher in patients with left versus right adrenal locations (P = 0.004). Patients with neuroblastoma on post-surgical histology lost more IDRFs (median: 1[0-9]) than patients with ganglioneuroblastoma (median: 0[0-4]) (P < 0.001). The completeness of resection was related only to the number of preoperative IDRFs (P = 0.028). IDRF assessment after neoadjuvant chemotherapy is useful for predicting completeness of resection of neurogenic tumors. A larger international study is needed to confirm these results and to explore a possible correlation between preoperative IDRF status and survival.

Irtan S ，Brisse HJ ，Minard-Colin V ，Schleiermacher G ，Galmiche-Rolland L ，Le Cossec C ，Elie C ，Canale S ，Michon J ，Valteau-Couanet D ，Sarnacki S ... -  《-》

Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial.

Recently, an international expert group proposed revision of the International Neuroblastoma Staging System (INSS). Localized disease can be classified as L1 without and as L2 with image defined risk factors (IDRF published in JCO 2005; 23:8483-8489). Our aim was to evaluate IDRF for the prediction of resectability, complications, and outcome. Records of 520 localized neuroblastoma patients of the NB97 trial were reviewed. Patients were retrospectively classified as having IDRF or not. A total of 366 evaluable patients were then analyzed for extent and complications of surgery and the prognostic value of IDRF. Any IDRF was present in 26/160 of stage 1, 49/113 of stage 2, and 64/93 of stage 3 patients. Complete primary resection was achieved in 156/227 patients without IDRF and 43/139 patients with IDRF (P < 0.001). The frequency of complications was higher if any IDRF was present: 37/139 versus 33/227 (P = 0.006). Lack of IDRF was associated with better event free survival (3-year-EFS 86 +/- 2% vs. 75 +/- 4%, P = 0.010), whereas overall survival was similar (3-year-OS 98 +/- 1% vs. 96 +/- 2%, P = 0.462). EFS clearly depended on INSS stage (3-year-EFS 93 +/- 2% in stage 1, 78 +/- 4% in stage 2, and 69 +/- 5% in stage 3, P < 0.001). OS was not different (3-year-OS 98 +/- 1% vs. 99 +/- 1% vs. 94 +/- 2%, P = 0.056). Multivariate analysis demonstrated an impact of INSS stage on EFS only. IDRF were not shown to be significant for predicting EFS or OS. IDRF were useful in predicting risk and completeness of operation. IDRF failed as independent risk predictors in localized neuroblastoma. INSS more precisely identified patients with poor prognosis.

Simon T ，Hero B ，Benz-Bohm G ，von Schweinitz D ，Berthold F ... -  《-》

Natural history and biology of stage A neuroblastoma: a Pediatric Oncology Group Study.

PURPOSE:To prospectively analyze the outcome of patients with Stage A neuroblastoma (NB) treated with surgery alone, especially with regard to the prognostic significance of age, tumor site, MYCN copy number, tumor cell ploidy, and histology. PATIENTS AND METHODS:The clinical course of 329 patients with Stage A disease registered on the POG NB Biology Study #9047 between February, 1990 and October, 1997 were evaluated. Age, tumor site, MYCN copy number, tumor cell ploidy, and histology were analyzed for their impact on event-free survival (EFS) and survival (S). RESULTS:The 5-year estimated EFS and S rates for the 329 patients were 91% (+/-3%) and 96% (+/-2%), respectively. The EFS rate was similar for infants younger than 12 months and children age 12 months or older, but age older than 12 months was predictive of lower S rates (P = 0.044). Patients with adrenal, abdominal non-adrenal, thoracic, and cervical tumors had similar S rates. The majority of patients had tumors with favorable biologic features, and only 3% had MYCN amplification. For infants with diploid tumors, the EFS rate was 82% (+/-16%), but effective therapy yielded an S rate of 100%. Rate of S was 80% (+/-26%) and 64% (+/-27%) for patients with unfavorable tumor histology and MYCN-amplified tumors, respectively. CONCLUSION:The outcome for patients with Stage A NB treated with surgery alone is excellent. Although EFS and S rates were significantly worse for patients with MYCN-amplified tumors, a subset achieved long-term remission after surgery alone. For patients with Stage A and MYCN amplification, additional factors are needed to distinguish the patients who will achieve long-term remission with surgery alone from those who will develop recurrent disease.

Alvarado CS ，London WB ，Look AT ，Brodeur GM ，Altmiller DH ，Thorner PS ，Joshi VV ，Rowe ST ，Nash MB ，Smith EI ，Castleberry RP ，Cohn SL ... -  《JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY》

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

Fischer J ，Pohl A ，Volland R ，Hero B ，Dübbers M ，Cernaianu G ，Berthold F ，von Schweinitz D ，Simon T ... -  《BMC CANCER》