UTILITY OF BONE MARROW ASPIRATION AND BIOPSY (BMAB) IN INITIAL STAGING OF EWING SARCOMA (EWS) Lisa M. Kopp, Winston W. Huh, Cynthia E. Herzog, Chengcheng Hu, Andrea White-Collins, Beatriz Rozo, Angela Yarborough, Pooja Hingorani

Background Pediatric and adolescents patients with newly diagnosed Ewing Sarcoma (EWS) have a bilateral bone marrow aspiration and biopsy (BMAB) performed as part of the initial staging evaluation BMAB is a painful procedure that is performed using general anesthesia Stressful for newly dx patients and can have complications

Background The NCCN guidelines on bone cancer recommend the option of either a BMAB or MRI of the spine and pelvis in newly diagnosed adult patients The necessity of a BMAB in staging pediatric and adolescent EWS patients in addition to radiological evaluation has not been previously established

Objectives To evaluate the association between imaging determined non-metastatic EWS and BM metastasis in pediatric and adolescent patients To evaluate the association between BM metastasis and other clinical characteristics of pediatric and adolescent EWS patients

Methods Retrospective review involving 3 institutions Eligibility: Patients less than 40 years of age with newly diagnosed EWS between the years 2000-2012; available initial staging scans and BM evaluation 116 patients Initial staging reviewed Imaging (MRI primary site, CT chest, Bone scan) Bone Marrow Aspiration and Biopsy

Patient Characteristics Non-metastatic (n=85) Metastatic (n=31) Gender Male Female 47 (55.3%) 38 (44.7%) 18 (58.1%) 13 (41.9%) Age at Diagnosis* 13 (1, 38) 16 (3, 25) Primary Tumor Site Pelvis Non-pelvis 15 (17.6%) 70 (82.4%) 14 (45.2%) 17 (54.8%) Primary Tumor Size (cm)*, ** 7.5 (1.3, 26.0) 11.2 (3.5, 35.0) * Median (range) ** Primary tumor size of metastatic patients was significantly higher that that of non-metastatic patients (p-value = 0.017 by Wilcoxon rank-sum test)

Metastatic Patients Metastatic site: Patients with multiple metastatic sites: Lung alone Bone alone BM alone Multiple 13 (41.9%) 2 (6.5%) 0 (0.0%) 16 (51.6%) Lung Bone BM Lymph Nodes 9 (56.3%) 14 (87.5%) 13 (81.3%) 2 (12.5%)

BMAB Results None of the 85 non-metastatic patients determined by imaging had positive BMAB A positive pelvic primary site was not correlated with a positive bone marrow BMAB Correlation with pelvic primary site (n=116) Pelvic Non-Pelvic P-value BMAB positive 6 7 0.087 BMAB negative 23 80

Number of Bony Metastatic Sites (bone scan, n=28) BMAB Results 13 of 31 metastatic patients by imaging had positive BMAB Number of Bony Metastatic Sites (bone scan, n=28) BMAB positive BMAB negative P-value 3.5 (1.0, 11.0) 0.0 (0.0, 2.0) < 0.0001 None of the 85 non-metastatic patients as determined by imaging The number of boney mets by bone scan was missing for 3 of the patients – n =28 # bony sites per person for the 28 people – BMAB Median 3.5 bony sites(range). BMAB neg median bony mets – being BMAB positive more likely bony sites

Association of Metastasis by Imaging and BMAB BMAB Results Bone Metastasis Lung Metastasis Yes No Positive 12 1 6 7 Negative 4 14 16 2 P-value for association* 0.0002 0.017 *Fisher’s exact test was used to evaluate association. It appears that having bone metastasis positive correlation to have bone metastasis Having lung mets had a neg correlation with positive bone marrow aspiration biopys

Conclusion Pediatric and adolescent Ewing sarcoma patients with non-metastatic disease by imaging may have a bone marrow aspiration and biopsy eliminated as part of initial staging In patients with metastatic disease there is a high correlation between bone marrow metastasis and the number of bony metastatic sites

Acknowledgments University of Arizona Winston W. Huh, MD University of Texas MD Anderson Cancer Center Children’s Cancer Hospital Phoenix Children’s Hospital Pooja Hingorani, MD Andrea White-Collins, NP University of Arizona – Mel and Enid Zuckerman College of Public Health Chengcheng Hu, PhD Winston W. Huh, MD Cynthia E. Herzog, MD, MPH Beatriz Rozo, NP Angela Yarbarough, NP