Neuroblastoma

Elizabeth RobertsData Coordinator

CIBMTR Data Managers Mentor

Elizabeth RobertsData Coordinator

CIBMTR Data Managers Mentor

Tandem Meeting February 18

Objectives

• Know what neuroblastoma is, how it is diagnosed, and how it is treated

• Complete form 2026: Neuroblastoma Pre-HSCT Data

• Complete form 2126: Neuroblastoma Post-HSCT Data

About My Center• Pediatric Center, performing

average of 100 transplants per year. First transplant performed in 1981

• Three Data Coordinators, specializing in disease-specific areas

• We use Epic for our electronic records

What Is Neuroblastoma?

• Starts in very early forms of nerve cells (neuroblasts) of the sympathetic nervous system

• Neuro = nerves• Blastoma = cancer

Common Neuroblastoma Sites

• Adrenal glands• Abdomen (non-

adrenal)• Chest• Pelvis• Neck

Neuroblastoma Statistics

• 8-10% of all childhood cancers• ~8 children per million per year under

age of 15 diagnosed• Median age of diagnosis is 22 month• More than 95% of cases are detected

by 10 years of age

How Is Neuroblastoma Diagnosed?

• Blood and urine catecholamine tests• Imaging tests• Biopsy of tumor site• Bone marrow aspiration and biopsy

Catecholamine Tests

• Detected in more than 85% of patients with NBL

• Homovanillic Acid (HVA)• Vanillymandelic Acid (VMA)

Imaging Tests

• CT scans – usually abdomen, pelvis, and chest

• MRI scans – usually brain and spine• MIBG scans – preferred by many

doctors as the standard test• PET scans

Biopsy

• Tissue is often needed to obtain all data required for risk-group assignment and treatment stratification in COG clinical trials

Bone Marrow Aspiration/Biopsy

• Determine extent of disease/staging

Neuroblastoma Staging – INSS System

• Stage 1: Localized tumor with complete gross excision; lymph nodes negative for tumor microscopically

• Stage 2A: Localized tumor with incomplete resection; lymph nodes negative

• Stage 2B: Localized tumor with or without complete resection; ipsilateral lymph nodes positive

• Stage 3: Unresectable unilateral tumor infiltrating across the midline; or localized unilateral tumor with contralateral positive lymph nodes

• Stage 4: Disseminated disease (except 4S)• Stage 4S: Localized primary tumor with dissemination limited to

skin, liver and/or marrow (<10%) (infants < 1yr)

Neuroblastoma and the MYCN Oncogene

• Amplification of MYCN occurs in ~20% of primary untreated NB tumors, and is associated with:– Advanced stage disease (Science, 1984)– Rapid tumor progression and poor

prognosis (N. Engl. J. Med., 1985)– High levels of MYCN expression (Science,

1984)

What Therapies Do We Use to Treat Neuroblastoma?

• Surgery/biopsy• Chemotherapy• Second look surgery• ASCT• Radiation therapy• Cis-Retinoic therapy• Immunotherapy

Surgery

• Remove as much tumor as possible• Dependent on proximity to vital

structures or blood vessels• Chemotherapy may be used to shrink

the tumor first

Chemotherapy

• Commonly used when metastases involved

• May be before (neoadjuvant) or after (adjuvant) surgery

• Most common drugs: carboplatin (or cisplatin), cyclophosphamide, doxorubicin, and etoposide in cycles

Stem Cell Transplant

• High-risk patients• High doses of chemotherapy are

effective in treating NBL, but also severely damage bone marrow

• Need to give stem cells to replace those that were lost

• Use patient’s own cells (autologous transplant)

Radiation Therapy

• External Beam – Aimed at tumor only– Can be used to shrink tumor before

surgery– Sometimes part of treatment regiment

before stem cell transplant• MIBG Therapy – Delivers radiation

directly to tumor via blood stream

Retinoid Therapy

• Related to Vitamin A• Differentiating Agents – Help cancer

cells differentiate into normal cells• Currently use 13-cis-retinoic acid

Immunotherapy

• Typically used in high-risk patients• Helps immune system recognize and

destroy cancer cells more effectively• Monoclonal antibodies given with

cytokines

Filling Out the Forms

• Form 2026 is for Pre-HSCT data• Form 2126 is for Post-HSCT data

Form 2026: Clinical and Laboratory Characteristics at Diagnosis

• Diagnosis Date - Pathology

Form 2026: Clinical and Laboratory Characteristics at Diagnosis

Form 2026: Clinical and Laboratory Characteristics at Diagnosis

Form 2026: Clinical and Laboratory Characteristics at Diagnosis

• Use pathology report for sites of primary disease

• Metastases• Radiographic tests – in Epic, Radiology

tab• Biopsies – Pathology tab• Shimada Classification – Pathology

report

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

• HVA and VMA in Urine Chemistry. We send ours out

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

• N-myc amplification - Supplementary pathology report

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

• Cytogenetic Analysis – Our center tends to not perform these on NBL patients

• INSS – most centers use this, but if yours uses POG or Evans, report those. Noted on supplemental report

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

Form 2026: Laboratory Values at Diagnosis of Neuroblastoma

• Surgery• Radiotherapy• Chemotherapy – Oncology road maps• Best Response – Pathology reports

Form 2026: Line of Therapy

Form 2026: Disease Status Immediately Prior to Preparative Regimen

Form 2126: Disease Assessment at Time of Best Response to HSCT

• Planned Therapy• Radiotherapy – End of Treatment Note• Retinoids• Immunotherapy• Chemotherapy

Form 2126: Disease Assessment at Time of Best Response to HSCT

Form 2126: Disease Assessment at Time of Best Response to HSCT

Form 2126: Disease Assessment at Time of Best Response to HSCT

Form 2126: Disease Assessment at Time of Best Response to HSCT

Form 2126: Disease Assessment at Time of Best Response to HSCT

• Recurrence/Progression – Pathology• Treatment for persistent, progressive, or

recurrent disease

References• American Cancer Society. Cancer Facts and Figures 2015.

Atlanta, Ga: American Cancer Society; 2015.• Cheung NK, Dyer MA. Neuroblastoma: Developmental biology,

cancer genomics and immunotherapy. Nat Rev Cancer. 2013; 13:397-411.

• Grupp SA, Dvorak CC, Nieder ML, et.al. Children’s Oncology Group’s 2013 blueprint for research: Stem cell transplantation. Pediatr Blood Cancer. 2013; 60:1044-1047

• National Cancer Institute. Pysician Data Query. Neuroblastoma Treatment. 2013. Accessed at www.cancer.gove/cancertopics/pdq/treatment/neuroblastoma/healthprofessional on 2/4/16.

• Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010; 363:1324-1334.

Questions?