Image-guided core needle biopsy for relapsed and refractory neuroblastoma: A focus on sample adequacy for genetic sequencing.

Abstract

e22521 Background: Relapsed and refractory neuroblastoma (NBL) is a prime target for novel therapies targeting specific mutations. The genomic landscape of NBL can change between time of initial diagnosis and relapse, necessitating subsequent biopsy and next generation sequencing (NGS) to detect mutations within the relapsed neoplasm. Tissue of insufficient quality and quantity leads to specimen failure during NGS. Thus the goal of this study is to review core needle biopsy for relapsed and refractory NBL in a pediatric interventional radiology department and explore factors that enhance biopsy adequacy. Methods: Retrospective review of clinical records and images for 66 patients (36M, 30F) with median age 8.7 years (range 0.9 – 49.3 y) who underwent 95 biopsies (55 bone, 40 soft tissue) over a 12-year period. Results: Biopsy yield for neuroblastic tissue from 123I mIBG-avid masses was 89.7% overall, 84.9% in bone, and 91.6% in soft tissue. 87/95 masses were mIBG-avid; 2 non-avid masses were NBL-positive (but also 18F-FDG avid). 48/59 samples sent for NGS were adequate for analysis (81.4%); bone and soft tissue biopsies did not differ in adequacy (77.1% vs 87.5%, p = 0.32). Tumor cell percent (TC%) for adequate samples was 49.9% vs 11.1% for NGS failures (p = 0.0003). Number of needle passes performed in bone and soft tissue lesions was positively correlated with NGS adequacy (Bone: r2= 0.68, Soft: r2= 0.33). In bone and soft tissue, adequate biopsies tended towards higher mean needle passes than inadequate ones (Bone: 5.1 vs 3.4, p = 0.0582) (Soft: 10.5 vs 4.7, p = 0.0428). Total needle volume passed into a soft tissue mass (calculated as inner needle cylindrical volume * # of passes) was higher in the “adequate” vs “inadequate” group (0.20 cm3 vs 0.05 cm3, p = 0.0004). Lesion mIBG avidity was quantified with a ratio of lesion:liver SUV; this mIBG SUV ratio was positively correlated with TC% (R2 = 0.55, N = 14). Using a linear regression line, a TC% of 50% (the mean value for samples adequate for NGS) corresponded to an SUV ratio of 2.89. The rate of minor complications (requiring only nominal therapy) was 7/95 (7.4%). The rate of major complications (requiring longer hospital stay) was 1/95 (1.5%). Conclusions: Image-guided core needle biopsy for relapsed and refractory NBL has a moderately high yield for procuring tumor samples adequate for NGS with a low rate of major complications. Adequate bone and soft tissue biopsies averaged >5 and >10 needle passes, respectively. An approximate lesion:liver mIBG SUV ratio of >3 may maximize specimen quality for NGS.