Background and Aims

Segmental chromosomal aberrations (SCA) and MYCN amplification (MNA) are biomarkers for risk-group stratification in neuroblastoma, currently assessed on tissue biopsy. Increase in demand for tumour genetic testing for neuroblastoma diagnosis is posing a challenge to current practice, as the small size of the core needle biopsies obtained are required for multiple molecular tests.

Objective: To investigate the utility of circulating free DNA (cfDNA) in patients with neuroblastoma for molecular risk-stratification.

Methods

Various pre-analytical conditions were tested to optimize cfDNA for SNP microarray currently used for neuroblastoma diagnosis. Plasma samples from 12 patients diagnosed with neuroblastoma were assessed for SCA and MNA using the Infinium CytoSNP-850K Beadchip array, with MNA status assessed independently using digital-droplet PCR (ddPCR).

Results

cfDNA samples generally yield highly degraded DNA and thus perform poorly in array-based applications such as SNP whole-genome genotyping. This could be overcome using pre-analytical DNA repair procedures, reaching a limit of detection of 20% variant allele frequency (VAF) for SCA, and 10% for MNA (our lowest tested VAF). MNA detection is highly affected by physical perturbations of the blood sample (mimicking sample shipment), which could be overcome using specialized collection tubes.

11/12 (92%) patients tested positive for SCA using SNP array: 8/8 (100%) and 1/2 (50%) at initial diagnosis with metastatic and localised disease, respectively, and 2/2 (100%) at metastatic relapse; of which 7 also presented MNA. cfDNA and matched tumour DNA profiles were generally identical. 7/7 (100%) of MNA and 0/5 (0%) non-MNA cases were tested positive using ddPCR.

Conclusions

These results reflect the feasibility of ctDNA SCA profiling in molecular risk-stratification, with MNA status orthogonal conformation via ddPCR in a clinically relevant time frame, and suggest that ctDNA analysis could potentially reduce tissue requirements currently embedded in the management of NB.

Background and Aims

Surgery is integral to the local management of high-risk neuroblastoma (HRN). Imaging-defined risk factors (IDRF) are used to classify tumours into surgical risk groups but do not define tumour extent based on location. We propose a novel classification based on abdominal zones (AZ) to better characterise these tumours.

Methods

We conducted a retrospective review of consecutive HRN patients that underwent surgery at a single paediatric oncology unit between January 2008 and December 2019. We collected clinical data including details of tumour location/extent on imaging prior to surgery. The abdomen was divided into eight AZ based on anatomical landmarks. Analysis was performed to determine whether tumour distribution within these AZ affected peri-operative outcomes, event-free survival (EFS) and overall survival (OS).

Results

A total of 84 HRN children underwent surgery. Median age (range) at diagnosis was 2.5 (1.5-4.3) years. Preliminary analysis indicated that the total number of “tumour-positive” AZ impacted outcomes but did not correlate with IDRF number (r=0.3, p=0.1). Based on ROC analysis, patients were divided into 2 groups; G1: tumour in ≤2 AZ (n=36), and G2: tumour in ≥3 AZ (n=48). There were no differences between groups on baseline parameters (including number of IDRF; p=0.08), but only 5 G1 patients (14%) had involvement of midline AZ (96% in G2, p<0.0001). Complete resection was achieved in 71% of G2 children (100% in G1, p=0.008), who also had higher incidence of intra-operative complications (including bleeding; p=0.002). G2 patients had worse EFS [48% vs. 72% in G1; OR (95%CI): 0.4 (0.1-0.9), p=0.02] and OS [46% vs. 94% in G1; OR (95%CI): 0.05 (0.01-0.2), p<0.0001].

Conclusions

Tumour location/extent defined by AZ correlated to surgical complications and outcomes despite a comparable number of IDRF. This AZ classification may allow clearer comparison of tumours and better prediction of surgical complexity than IDRF alone.

Background and Aims

The role of surgery in neuroblastoma (NBL) and peripheral neuroblastic tumors (pNBT) such as ganglioneuroblastoma, is diagnostic (biopsy) or therapeutic (resection). Due to various tumor locations and frequent adherence or encasement of vascular or neural structures and vital organs, surgery in NBL & pNBT may be challenging, with important operative morbidity and mortality. The hazards of surgery and its complications in NBL & pNBT are not well described and its role in the treatment of high-risk disease remains debated. To optimize the recording of important perioperative data and intra- and postoperative outcomes, a standardized surgical case report form was created with international consensus.

This presentation aims to make pediatric surgical oncologists acquainted with the standardized surgical report form and will demonstrate its correct use. It also aims to stimulate its use in routine clinical practice, to engage all colleagues for structured reporting of NBL & pNBT surgery.

Methods

The "International Neuroblastoma Surgical Report Form" (I.N.S.R.F.) was published in 2020 as a joint initiative by the surgical committees of the pediatric oncological cooperative groups SIOPEN, COG and GPOH. We created a short instructive video to demonstrate its correct use in clinical practice, in a step-by-step approach.

Results

The brief instructive video will demonstrate clearly the correct and straightforward use of the I.N.S.R.F. in clinical practice. The different parts of the I.N.S.R.F. offer structured and standardized recording of important perioperative data and of intra- and postoperative complications.

Conclusions

The I.N.S.R.F. provides standardized recording of important perioperative data in NBL & pNBT surgery in a structured and straightforward manner. Its correct use is demonstrated in a short instructive video. Routine use of the I.N.S.R.F. in clinical practice, to document every surgical procedure for NBL or pNBT, is highly recommended, as it will ensure surgeon connectivity, facilitate surgical outcome analysis and improve clinical care.

Background and Aims

We hypothesize that meso-Rex bypass (MRB) or portosystemic shunt (PSS) are effective at relieving portal venous (PV) obstruction secondary to malignant disease in children.

Methods

Ten patients with PV obstruction and periportal malignancy underwent a MRB or PSS (1997-2019, IRB 2006-12729). Paired and independent t-tests were used for comparison (p<0.05 considered statistically significant).

Results

Patients presented the following tumors: five hepatoblastomas, one undifferentiated embryonal sarcoma of the liver (UESL), one bile duct rhabdomyosarcoma, one pancreatic neuroendocrine tumor, one yolk sac tumor, and one ganglioneuroblastoma. Four children had tumor excision and PV reconstruction simultaneously while six were done sequentially. Mean age at tumor excision was significantly younger in the sequential group (4.2years±2.7 vs. simultaneous 9.8years±3.3, p=0.024). Mean age at diagnosis of venous obstruction was similar in both groups (sequential 6.0years±4.6 vs. simultaneous 9.2years±3.2, p=0.26). Mean age at PV surgery was similar (sequential 10.2years±6.1 vs. simultaneous 9.8years±3.3, p=0.91). 4 patients had symptomatic variceal bleeding and 5 advanced hypersplenism prior to PV surgery. 8 patients underwent a primary MRB; one thrombosed and was converted to a PSS. Two patients underwent a primary PSS because no suitable intra-hepatic PV was present. There was no difference in mean age at PV surgery between types of PV procedure (MRB 8.9years±4.0 vs. PSS 12.9years±6.6, p=0.26). Overall, median length of follow up was 1.5 year (21 days-8.5 years). There was no recurrence of variceal bleeding. Palpable spleen size diminished (8.6cm±4.5 to 1.0cm±1.7, p=0.011) and platelet count increased (75.4thou/uL±43.3 to 135.2thou/uL±65.5, p=0.01) significantly after PV surgery. One patient died (UESL recurrence). All others survived with patent vascular bypasses and no tumor recurrence at last follow-up.

Conclusions

We conclude the meso-Rex bypass can successfully restore portal circulation after venous obstruction from malignant disease without adversely affecting oncological outcomes. Portosystemic shunts can offer similar palliation if the meso-Rex bypass option is not available.