International Neuroblastoma Risk Group Staging Research Articles

A review of neuroblastoma image-defined risk factors on magnetic resonance imaging.

Neuroblastoma is the most common extracranial solid malignancy in children. Historically, neuroblastoma has been staged using the International Neuroblastoma Staging System (INSS), which relies on surgical staging. This is problematic because surgical resection can vary among surgeons and tumors and occurs at interval times from diagnosis. In 2009 the International Neuroblastoma Risk Group (INRG) created a new staging system that relies on preoperative imaging for staging. The INRG staging system consists of 20 image-defined risk factors (IDRF) across multiple organ systems, which help predict surgical outcomes/adequacy of resection and can be combined with clinical data to provide up-front risk stratification. The purpose of this review is to describe both the INSS and INRG staging systems and their limitations and to illustrate the definitions and IDRFs that comprise the INRG staging system.

Role of Multi-Slice CT in Staging of Neuroblastoma

Background: The International Neuroblastoma Risk Group Staging System (INRGSS) is a recent pretreatment staging system for neuroblastoma (NB), based on imaging by CT before surgery. Purpose: this study aimed to stage NB cases using CT scan, in relation to available clinicopathologic data. Patients and Methods: Twenty pathologically proven NB cases were included. All were reviewed for patients' characteristics, includingage; sex, clinical picture, LN status and metastatic spread. All cases underwent CT scan for diagnosis. Stagingwas done using IDRFs, LN status and metastatic spread according to the INRGSS and INSS when available. Results: an abdominal mass was found in 85% of cases and the suprarenal gland was the most common site of primary tumor (50% of cases). Concerning tumor grade, 85 % of cases were poorly differentiated. LNs were positive in 70%, and metastatic spread was found in 35% of patients respectively. Staging according to the INRGSS showed that L2 was the most common stage (45% of cases), followed by M stage (35%). L1 and MS stages were found in 15% and 5% of cases respectively. Only 7 cases had postsurgical CT scans, and were staged according to the INSS. Conclusion: it was concluded that the use of the INRGSS using CT scan, is a recent valuable pretreatment staging system, allowing accurate classification of neuroblastoma.

A Case of Retroperitoneal Primary Neuroblastoma that Developed in Adulthood

Neuroblastoma is a solid malignant tumor found in young children period, but it may also develop in adulthood. Adult neuroblastoma is rare in Japan (incidence of at least 1/100 million). Here, we report on an adult with retroperitoneal primary neuroblastoma. A 32-year-old woman presented with a chief complaint of abdominal tumor diagnosed as neuroblastoma on needle biopsy. The tumor markers for neuroblastoma were 32.6 ng/ml for neuron specific enolase, 30.1 μg/mg Cr for urine vanillylmandelic acid and 42.3 μg/mg Cr for urine homovanillic acid. Imaging showed metastasis to the mediastinal lymph nodes, but bone metastases were not found. The International Neuroblastoma Risk Group Staging System classification for this neuroblastoma was stage M. The tumor involved the left renal artery and aorta. The case was positive for image defined risk factors. Therefore, the patient received three courses of cyclophosphamide, pirarubicin, vincristine, and cisplatin. Tumor shrinkage was noted. We recommended continued chemotherapy, and bone marrow transplantation, but the patient refused further chemotherapy due to the serious side effects of chemotherapy. Tumor extirpation was judged possible by resection of the left renal tumor using a retroperitoneal mirror in combination. The excised tumor was more ganglion-like than at biopsy, and a stroma-rich portion was recognized, which was thought to be maturation due to chemotherapy. MYCN gene amplification was absent. Postoperatively, radiotherapy of the tumor bed and mediastinal lymph nodes was performed and the patient was followed-up. Many adults refuse chemotherapy, which makes sufficient treatment difficult. In adults, even when MYCN gene amplification is not allowed, sufficient observation is necessary since prognosis is the poor.

Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells) and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma) in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site), some histological, molecular biochemical (ploidy) and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc.) characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes) and intrachromosomal (homogenically painted regions). Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed) from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the biological behavior of neuroblastoma, which are untypical of other tumors; histological structure; determinants of the prognosis of the disease, including MYCN gene status; and mechanisms for formation of the amplification and elimination of amplified sequences from the nucleus.

Image-defined Risk Factors Correlate with Surgical Radicality and Local Recurrence in Patients with Neuroblastoma.

Neuroblastoma is the second most common solid pediatric tumor and the most common cancer to be detected in children younger than 12 months of age. To date, 2 different staging systems describe the extent of the disease: the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Risk Group Staging System (INRGSS). The INRGSS-system is characterized by the presence or absence of so called image-defined risk factors (IDRFs), which are described as surgical risk factors. We hypothesized that IDRFs correlate with surgical complications, surgical radicality, local recurrence and overall survival (OS). Between 2003 and 2010, 102 patients had neuroblastoma surgery performed in our department. We analyzed medical records for IDRF-status and above named data. 16 patients were IDRF-negative, whereas 86 patients showed one or more IDRF. Intra- or postoperative complications have been reported in 21 patients (21%). 19 of them showed one or more IDRF and 2 patients were IDRF-negative (p=n.s.). Patients who suffered from intra- or postoperative complications demonstrated a decreased OS (p=0.011). Statistical analysis revealed an inverse correlation between the extent of macroscopical removal and IDRF-status (p=0.001). Furthermore, the number of IDRFs were associated with a decreased likelihood of radical tumor resection (p<0.001). 19 patients had local recurrence; all of them were IDRF-positive (p=0.037). Pediatric surgeons should consider IDRFs as a useful tool for risk assessment and therefore planning for neuroblastoma surgery.

Multidisciplinary management of cervical neuroblastoma in infants

ObjectivesNeuroblastoma is the most common malignancy in infancy, it is a histologically and genetically heterogeneous tumor, the therapy and outcome of which is influenced by age, histological variant and genetic background as well. MethodsWe present two consecutive infant patients with neuroblastoma of the neck discussing the etiology, the diagnosis and the surgical and oncological treatment of the tumor, which was observed in a relatively rare manifestation in the head–neck region. ResultsOur first patient (age: 5.5 months) was MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived) negative, INSS (International Neuroblastoma Staging System) Stage 3 and INRGSS (International Neuroblastoma Risk Group Staging System) Stage 3 because of the contralateral lymph node involvement while the complete gross resection of the primary tumor mass was feasible. The patient is tumor free after three years of follow-up. Our second patient (age: 5 months) was MYCN negative, INSS Stage 2 and INRGSS Stage 1, as both the primary tumor and the ipsilateral lymph nodes were totally removed via a modified radical neck dissection. The patient is tumor free after three years of follow-up. ConclusionFor MYCN negative patients, especially in early age, the prognosis of neuroblastoma is good, surgical resection and chemotherapy together is an adequate treatment protocol (as in our two patients). While MYCN-amplified patients require a combined and aggressive treatment with surgery, chemotherapy, radiotherapy, and immunotherapy to be able to obtain a favorable survival rate according to the literature.

New semi-quantitative 123I-MIBG estimation method compared with scoring system in follow-up of advanced neuroblastoma: utility of total MIBG retention ratio versus scoring method

The purpose of this study is to evaluate a new semi-quantitative estimation method using (123)I-MIBG retention ratio to assess response to chemotherapy for advanced neuroblastoma. Thirteen children with advanced neuroblastoma (International Neuroblastoma Risk Group Staging System: stage M) were examined for a total of 51 studies with (123)I-MIBG scintigraphy (before and during chemotherapy). We proposed a new semi-quantitative method using MIBG retention ratio (count obtained with delayed image/count obtained with early image with decay correction) to estimate MIBG accumulation. We analyzed total (123)I-MIBG retention ratio (TMRR: total body count obtained with delayed image/total body count obtained with early image with decay correction) and compared with a scoring method in terms of correlation with tumor markers. TMRR showed significantly higher correlations with urinary catecholamine metabolites before chemotherapy (VMA: r(2) = 0.45, P < 0.05, HVA: r(2) = 0.627, P < 0.01) than MIBG score (VMA: r(2) = 0.19, P = 0.082, HVA: r(2) = 0.25, P = 0.137). There were relatively good correlations between serial change of TMRR and those of urinary catecholamine metabolites (VMA: r(2) = 0.274, P < 0.001, HVA: r(2) = 0.448, P < 0.0001) compared with serial change of MIBG score and those of tumor markers (VMA: r(2) = 0.01, P = 0.537, HVA: 0.084, P = 0.697) during chemotherapy for advanced neuroblastoma. TMRR could be a useful semi-quantitative method for estimating early response to chemotherapy of advanced neuroblastoma because of its high correlation with urine catecholamine metabolites.

Guidelines for Imaging and Staging of Neuroblastic Tumors: Consensus Report from the International Neuroblastoma Risk Group Project

Neuroblastoma is an enigmatic disease entity; some tumors disappear spontaneously without any therapy, while others progress with a fatal outcome despite the implementation of maximal modern therapy. However, strong prognostic factors can accurately predict whether children have "good" or "bad" disease at diagnosis, and the clinical stage is currently the most significant and clinically relevant prognostic factor. Therefore, for an individual patient, proper staging is of paramount importance for risk assessment and selection of optimal treatment. In 2009, the International Neuroblastoma Risk Group (INRG) Project proposed a new staging system designed for tumor staging before any treatment, including surgery. Compared with the focus of the International Neuroblastoma Staging System, which is currently the most used, the focus has now shifted from surgicopathologic findings to imaging findings. The new INRG Staging System includes two stages of localized disease, which are dependent on whether image-defined risk factors (IDRFs) are or are not present. IDRFs are features detected with imaging at the time of diagnosis. The present consensus report was written by the INRG Imaging Committee to optimize imaging and staging and reduce interobserver variability. The rationales for using imaging methods (ultrasonography, magnetic resonance imaging, computed tomography, and scintigraphy), as well as technical guidelines, are described. Definitions of the terms recommended for assessing IDRFs are provided with examples. It is anticipated that the use of standardized nomenclature will contribute substantially to more uniform staging and thereby facilitate comparisons of clinical trials conducted in different parts of the world.

Imaging neuroblastoma: what the radiologist needs to know

Neuroblastoma is the most common extracranial solid malignancy in children. The tumor has variable biological behavior that can be predicted by patient age, genetic features, tumor biology and extent of disease at diagnosis. Factors chosen by various cooperative groups to define risk of treatment failure have been non-uniform. Therefore, historically, it has been difficult to compare outcomes across clinical trials performed around the world. This has hindered the advancement of treatment strategies to improve survival of these patients. The International Neuroblastoma Risk Group (INRG) was established in 2004 to develop a consensus approach to pretreatment risk stratification. The result was the development of the INRG Staging System (INRGSS) which relies on imaging-defined risk factors (IDRFs) that are determined before surgery or other therapy. With the application of the INRGSS the radiologist's role in staging children with neuroblastoma is increased. This review provides an overview of the INRGSS and the IDRFs.

The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report

Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to < or = 85%, > or = 50% to < or = 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.

The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.