4/9/18. Disclosure Information. Objectives. Overview of Neuroblastoma Management. I have no disclosures.

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1 Overview of Neuroblastoma Management Lauren Martino, RN, MSN, CPNP Pediatric Surgery Nurse Practitioner Memorial Sloan-Kettering Cancer Center Disclosure Information I have no disclosures. Objectives Describe the typical treatment regimen for a patient with high risk neuroblastoma Identify the chemotherapy agents use in the treatment of neuroblastoma Recognize surgical considerations for the oncology patient undergoing surgery 1

2 l Neuroblastoma is a solid malignant tumor derived from neural crest cells l Majority arise from adrenal gland, but can occur anywhere along the sympathetic chain l Most common malignancy in infancy l Approximately 650 children are diagnosed with NB each year in the United States l Major sites of metastasis: l Bone marrow, bone, distant lymph nodes Typically present in infancy or toddler years Common signs/symptoms: Abdominal pain Limping due to bony pain Weight loss or failure to thrive Periorbital ecchymosis Subcutaneous nodules Changes in kidney or bowel function Example of NB presentation 2.5 year old female presents with fever and loss of appetite, mass is palpated Sent to ED and work up begun with lab, and imaging Ultrasound or CT shows abdominal mass Admit to Heme-onc floor and continue work up 2

3 Work-up CT-CAP shows adrenal mass encasing aorta and renal vessels and abd lymphadenopathy. Incisional bx done via mini-laparotomy and bone marrow biopsy Abdominal biopsy + poorly differentiated NB Mediport placed and began treatment according to COG ANBL0532 (Children s Oncology Group) or N8 protocol if treated at MSKCC Risk stratification Pre-treatment Risk stratification takes into account: Age Stage INSS International Neuroblastoma Pathology Classification Biological Variables MYCN amplification Ploidy (DNA index) 11q del and 17 gain The above is combined to determine International Risk Grouping (INRG) The High Risk patient Combination of chemotherapy, surgery, radiation, and immunotherapy Typically, 3-5 cycles of neoadjuvant chemo Surgical resection Adjuvent chemotherapy +/- autologous stem cell transplant (COG) Radiation Monoclonal antibody (3F8 or 14.18) 13-cis-retinoic acid 3

4 MSKCC regimen (N8) Chemotherapy for patients with high risk tumors Cyclophosphamide Doxorubicin (CAV) Vincristine Etoposide Cisplatin (PVP) Chemotherapy is dose-intensive Cyclophosphamide Drug class: nitrogen-mustard derivative alkylating agent Major side effects: Hematura, hemorrhagic cystitis SIADH induced hyponatremia Metallic taste, n/v, hiccups Gonadal suppression, infertility Cardiomyopathy, pulmonary fibrosis Clinical considertions: strict I/O, hyper hydration, hold for urine SG <1.010, daily urinalysis and prn, Furosemide PRN for low urine output; administer with Mesna to protect bladder Doxorubicin Drug class: Anthracycline antineoplastic antibiotic Major side effects: Cardiac toxicity (acute and delayed pericarditis, cardiomyopathy, arrhythmia, decreased contractility) Dermatologic changes: facial flushing, peeling skin, radiation recall, damage to skin and surrounding tissue upon extravasation (VESICANT) Nausea/vomiting, mucositis Discoloration of urine Leucopenia, thrombocytopenia, anemia Clinical Considerations: Give through central line or secure IV, avoid direct sunlight, Dexrazoxane (cardioprotectant), mouth care, baseline echocardiogram 4

5 Vincristine Drug class: Vinca alkaloid Major side effects: Constipation, paralytic ileus Severe jaw pain Peripheral neuropathy Damage to skin, surrounding tissue (Vesicant) Clinical considerations: administer via central line or secure IV, bowel regimen, consider holding dose if no BM x 48 hours, drug interactions (major substrate of CYP3A4) Etoposide Drug class: Mitotic Inhibitor Major Side effects: Hypotension Facial flushing/ urticaria Leukopenia/thromboctopenia Secondary malignancy (acute leukemia) Clinical considerations: observe for signs of hypertension or hypersensitivity, medication is prone to crystallization Cisplatin Drug Class: heavy metal alkylating agent Major site effects: Severe n/v Renal insufficiency and electrolyte wasting Ototoxicity Leukopenia, thrombocytopenia Clinical considerations: creatinine clearance prior to each cycle, monitor electrolytes, IV hydration pre/post hydration, mannitol administration, anti-emetic pre-medications needed 5

6 Chemotherapy Agents Surgical resection Surgical resection at MSKCC is typically attempted after cycle 3 Adrenal tumors are resected using a thoraco-abdominal exploration so that major vasculature is visualized and controlled. Many of these tumor encase major vasculature; this approach aids in achieving a gross total resection while salvaging the major vessels Considerations for surgery Surgery take place between cycles of chemo WBC, hemoglobin, platelets typically decrease (nadir) 7-10 days post chemo Counts should be recovered prior to surgery: Absolute neutrophil count > 1000 Platelets > 100k Delay in timing of surgery can lead to progression of disease if too much time lapses between treatment cycles 6

7 Consolidation After completing chemotherapy and undergoing surgical resection, consolidation therapy is next step. MSKCC Eliminates stem cell transplant Immune therapy using 3F8 COG Single or double stem cell transplant Immune therapy using ch Immunotherapy eradicating MRD Anti-GD2 antibodies (ch14.18, 3F8) What is 3F8? Attach to ganglioside GD2(glycolipid on outer cell membrane) expressed on 100% of NB Expression on normal tissue is limited to neurons Signals neutrophils and macrophages to attack NB cells for antibody dependent cellular cytotoxicity and complement mediated cytotoxicity Limited by HAMA 7

8 3F8 Monoclonal murine antibody (mouse protein) or Humanized hybrid antibody Used in conjunction with granulocyte macrophage colony stimulating factor (GM-CSF) GM-CSF injection is given 5 days prior to therapy and through treatment week Given over 1 hour infusion 3-5 days a week 13-cis-retinoic acid (Accutane) alternates with cycles of antibody for a total of 6 cycles (differentiating agent) Antibody Based Immunity Side effects of both ch14.18 and 3F8 PAIN!! Hypersensitivity reactions Neuropathy (3f8) Capillary leak syndrome (ch14.18) During treatment patients may require IV antihistamines, pain medication (up to 4 doses of hydromorphone/morphine in minutes) and fluid boluses Given in outpatient setting by specially trained research RNs 8

9 References Cheung, N. V., Cheung, I. Y., Kushner, B. H., Ostrovnaya, I., Chamberlain, E., Kramer, K., & Modak, S. (2012). Murine Anti-GD2 Monoclonal Antibody 3F8 combined cith granulocyte-macrophage colony-stimulating factor and 13-Cis-Retinoic Acid in high-risk patients with stage 4 neuroblastoma in first remission. Journal of Clinical Oncology, 30(26), doi: /jco Kushner B.H., Cohn, s., Matthay, K., Cheun, N.V., La Quaglia, M.P., Wolden, S., Ambros, P. (2005) Treatment of Neuroblastoma. In N.K.V. Cheung & S.L. Cohn (Eds.), Neuroblastoma (pp ). Springer-Verlag: Berlin, Heidelberg. La Quaglia, M. P., Kushner, B., Su, W., Heller, G, Kramer, K., Abramson, S, Cheung, N. (2004). The impact of gross total resection on local control and survival in high-risk neuroblastoma. Journal of Pediatric Surgery, 39, Perry, M. C., Doll, D. C., & Freter, C. E. (2012). Perrys the chemotherapy source book (5 th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. Trissel, L. A. (2009). Handbook on injectable drugs (19 th ed.). Bethesda, MD: American Society of Health- System Pharmacists. Trachtenberg, B. H., Landy, D. C., Franco, V. I., Henkel, J. M., Pearson, E. J., Miller, T. L., & Lipshultz, S. E. (2011). Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatric Cardiology, 32(3), doi: /s Questions? 9