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 ... -  《-》

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 ... -  《-》

Results of a prospective clinical trial JN-L-10 using image-defined risk factors to inform surgical decisions for children with low-risk neuroblastoma disease: A report from the Japan Children's Cancer Group Neuroblastoma Committee.

The present study sought to reduce the incidence of treatment complications of low-risk neuroblastoma by using image-defined risk factors (IDRFs) to inform the timing of surgical resection. Eligible patients included children (<18 years of age) with stage 1 or 2 disease, children (<365 days of age) with stage 3 disease, and infants with stage 4S disease. In IDRF-negative cases, treatment was completed with surgical resection alone. In IDRF-positive cases, the timing of surgery was determined based on the IDRFs after low-dose chemotherapy with 2-3 of the following four drugs: vincristine, cyclophosphamide, pirarubicin, and carboplatin. The outcome measures were overall survival, progression-free survival, and adverse events. This study was registered with the UMIN Clinical Trials Registry (number 000004355). Of the 60 patients screened between 2010 and 2013, 58 eligible patients were enrolled; 32 were identified as IDRF negative at diagnosis while 26 were identified as IDRF positive and underwent induction chemotherapy. The 3-year overall and progression-free survival rates of the 58 patients were 100% and 82.8% (95% confidence interval: 70.3-90.3), respectively. Neutropenia was the most frequently reported grade 3 or 4 chemotherapy-related form of toxicity (41.7%). With regard to surgical complications, 2.5% of all patients developed pleural effusion and ascites as early complications, while only 2.5% developed renal atrophy as a long-term complication. No fatal toxicities were observed. Using IDRFs to inform surgical decision making for the treatment of low-risk neuroblastoma improved prognosis and reduced the incidence of long-term complications.

Iehara T ，Yoneda A ，Yokota I ，Takahashi H ，Teramukai S ，Kamijyo T ，Nakazawa A ，Takimoto T ，Kikuta A ，Yagyu S ，Ikeda H ，Nakagawara A ，Tajiri T ，Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG) ... -  《-》

Image-defined risk factors in unresectable neuroblastoma: SIOPEN study on incidence, chemotherapy-induced variation, and impact on surgical outcomes.

To evaluate the impact of image-defined risk factor (IDRF) modification after chemotherapy on surgical outcomes, event-free survival (EFS), and overall survival (OS) among patients enrolled in the European Unresectable Neuroblastoma (EUNB) study. IDRFs were assigned according to the corresponding surgical risk factors list reported in the database. Surgical outcomes, EFS, and OS were related to IDRF modification with chemotherapy. The predictive value of preoperative IDRF for surgical outcomes was analyzed. Cox proportional hazards models for EFS and OS, including preoperative IDRF, surgical outcomes, and other known clinical risk factors, were created. Of the 160 patients enrolled in the EUNB study, 143 patients met the inclusion criteria. A total of 228 IDRF were thus collected. Following chemotherapy, 76 (33%) IDRF disappeared in 32.2% of patients, 33 (14%) new IDRF appeared in 18.8% of patients, and 49% of patients did not show any IDRF change. Complete resection/minimal residual disease (71.2%) was more frequent among children who had disappearance/numerical reduction of IDRF (P = 0.005). Infiltration of the branches of the mesenteric artery was predictive of an unfavorable surgical outcome. Prolonged preoperative chemotherapy over five courses and encasement of the celiac axis and/or mesenteric artery origin impacted EFS and OS. The unchanged IDRF pattern in 50% of patients and the appearance of new IDRF during chemotherapy in approximately 20% of patients strengthens the idea that prolonged chemotherapy is useless for improving surgical resection in this population of patients. In addition, midline perivascular abdominal preoperative IDRF appeared to be predictive not only of surgical outcomes but also of EFS and OS.

Avanzini S ，Pio L ，Erminio G ，Granata C ，Holmes K ，Gambart M ，Buffa P ，Castel V ，Valteau Couanet D ，Garaventa A ，Pistorio A ，Cecchetto G ，Martucciello G ，Mattioli G ，Sarnacki S ... -  《-》

Unresectable thoracic neuroblastic tumors: Changes in image-defined risk factors after chemotherapy and impact on surgical management.

Neuroblastoma management in children is multimodal and depends on multiple factors, including the possibility of complete surgical resection. Image-defined risk factors (IDRFs) are used to assess the feasibility of primary surgery. We studied the changes in IDRFs after neoadjuvant chemotherapy for thoracic neurogenic tumors. We performed a multicenter review of 27 patients presenting with unresectable thoracic neurogenic tumors. Patients received neoadjuvant chemotherapy, according to their risk group. IDRF at diagnosis and before surgery were retrospectively analyzed by a radiologist and a surgeon, blind to the initial assessment. Surgical and oncologic outcomes were reviewed. None of the patients presented MYCN amplification, and 78 IDRFs were identified at diagnosis. Vascular IDRFs were the most frequent, with 28 vascular IDRFs detected in 18 patients, 22 of which disappeared after chemotherapy. Reductions of tumor volume were associated with a regression of IDRFs. Patients undergoing minimally invasive surgery had smaller tumor volumes than those undergoing open surgery, and no vascular IDRF. Two patients received two additional courses of chemotherapy to reduce tumor volume sufficiently for surgery. One patient with ganglioneuroblastoma underwent early surgery due to a lack of response to initial chemotherapy. Tumor volume reduction with neoadjuvant chemotherapy eliminates most IDRF in thoracic neurogenic tumors. Vascular IDRF are rapidly resolved at this site, making surgical resection and minimally invasive surgery possible.

Delforge X ，De Cambourg P ，Defachelles AS ，Haffreingue A ，Rod J ，Kassite I ，Chabani N ，Lauriot-Dit-Prevost A ，Gourmel A ，Arnaud A ，Duchesne C ，Thebaud E ，Leclair MD ... -  《-》