Neuroblastoma+(child)

Neuroblastoma is a neuroendocrine tumor that can arise from any neuro crest of the sympathetic nervous system. It usually originates from one of the adrenal glands, but it can also arise in the neck, chest, abdomen, or pelvis. [2] || Lymph nodes, bone, bone marrow, skin (or subcutaneous tissues), and liver are the most frequent sites. The lung and central nervous system do not usually have metastatic involvement. [1] || Stage I – Tumor confined to the organ or structure of origin Stage II – Tumor extending in continuity beyond the organ or structure of origin but not crossing midline; regional lymph nodes on the ipsilateral side Stage III – Tumor extending in continuity beyond the midline; possible involvement of regional lymph nodes bilaterally Stage IV – Remote disease involving the skeleton, bone marrow, soft tissue, and distant lymph node groups, etc. Stage IVS – Patients who would otherwise be in stage I or II but have remote disease confined to the liver, skin, or bone marrow (without radiographic evidence of bone metastases on a complete skeletal survey)
 * **Epidemiolgy:** || Neuroblastoma is the most commonly occurring malignancy in infants and the most common extracranial solid tumor that occurs in childhood. About 6509 cases occur in the United States each year. About fifty percent of neurooblastomas occur in children younger than two years old. It is seen more in Caucasian children than African American children and occurs more commonly in males than females.[1,2]
 * **Etiology:** || The main cause of neuroblastomas is still unknown, but it is linked to genetic mutations. Familial neuroblastomas are known to be caused by genetic mutations in the anaplastic lymphoma kinase gene. Recent studies have proposed a connection to parental influences during gestation. Alcohol consumption, smoking, and medicinal drug use during pregnancy may lead to the development of neuroblastomas found in newborns. [2] ||
 * **Signs & Symptoms:** || Common symptoms of neurblastomas are fatigue, loss of appetite, fever, and joint pain. The presenting symptoms are dependent on the location of the primary tumor and sites of metastases. Patients with tumors of the abdomen commonly present with a swollen belly and constipation. Tumors in the chest may cause breathing or respiratory symptoms. Tumors located close to the spinal cord may lead to generalized weakness, inability to stand, crawl, or walk. Also, tumors that arise in the bones near the orbit can cause distinct bruising and swelling.[2] ||
 * **Diagnostic Procedures:** || In addition to a complete physical examination, other diagnostic procedures such as bone marrow aspirate and biopsy, lab studies, liver function tests, CT/MRI, and ultrasound may also be included. [1] ||
 * **Histology:** || Neuroblastomas are derived from primitive neural crest cells arising from within sympathetic ganglia. Ganglioneuroma consists of mature ganglion cells, Schwann’s cells and nerve bundles and is benign in appearance and nature. Glioneuroblastoma represents both mature ganglion cells and undifferentiated neuroblasts. Neuroblastoma is composed of dense nests of hyperchromatic cells and is undifferentiated. [1] ||
 * **Lymph node drainage:** || Lymphatic drainage of neuroblastoma is most frequent in the nodes at the origin of the renal artery and interaorticovenous nodes. Drainage for the left adrenal neuroblastoma occur in the paraaortic nodes and the nodes around the hemiazygos vein. The paracaval nodes and nodes around the azygos vein occurs for the right adrenal neuroblastoma. [3] ||
 * **Metastatic spread:** || 60% of patients less than a year old present with localized disease, while 70% of patients over the age of one present with metastases.[1]
 * **Grading:** || There is no distinct grading system used. However grading systems usually describe the degree of differentiation. In regards to neural crest cells, there are three types of tumors recognized which represent different degrees of differentiation.[1] By definition a neuroblastoma is a tumor at the undifferentiated end of the spectrum of the neural crest tumors.[1] ||
 * **Staging:** || Evans and D’Angio [1]

Pediatric Oncology Group Stage A – Complete gross resection of primary tumor, with or without microscopic residual; intracavitary lymph nodes, not adhered to and removed with primary (nodes adhered to or within tumor resection may be positive for tumor without upstaging patient to stage C)  Stage B – Grossly unresected primary tumor; nodes and liver same as in stage A  Stage C - Complete or incomplete resection of primary; intracavitary nodes not adhered to primary histologically positive for tumor; liver as in stage A  Stage D – Any dissemination of disease beyond intracavitary nodes (i.e. extracavitary nodes, liver, skin, bone marrow, bone)

International

Stage 1 – Localized tumor confined to area of origin; complete gross excision, with or without microscopic residual disease; identifiable ipsilateral and contralateral lymph nodes negative microscopically. Stage 2A – Unilateral tumor with incomplete gross excision; identifiable ipsilateral and contralateral lymph nodes negative microscopically. Stage 3 – Tumor infiltrating across the midline with or without regional lymph node involvement; unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral regional lymph node involvement. Stage 4 – Dissemination of tumor to distant lymph nodes, bone, bone marrow, liver, and/or other organs (except as defined in stage 4S) Stage 4S – Localized primary tumor as defined for stage 1 or 2, with dissemination limited to liver and skin. || If a patient is treated to a dose less than 500cGy there chance of developing long-term side effects from radiation therapy are minimal; which is the case for infants. When patients receiving a radiation dose of 2000cGy or higher, typically these patients are older, will see a change in the bones or soft tissue either with a decrease or asymmetric growth. If the treatment area is in the thoracic region then lung fibrosis is a concern. [1] ||
 * **Radiation side effects:** || If patients are receiving chemotherapy during their radiation treatment or have a hyperfractionated irradiation schedule they may experience an increase in skin reaction and mucositis. If a child is of a young age they are more likely to develop problems from radiation therapy later on in life compared to children who are older. If the patient is treated with chemotherapy then there is a chance of developing radiation side effects and the ability to tolerate the chemotherapy is decreased. Skeletal anomalies that could include limb shortening and or spinal deformities for example kyphosis and scoliosis are dependent upon the age of diagnosis. [1]
 * **Prognosis:** || Patient age and tumor stage at presentation are important factors. Tumor presence in lymph nodes and poorly differentiated tumors are poor prognosis factors. [4] ||
 * **Treatments:** || Treatment ports should include the primary tumor plus a 2-3 cm margin, with care to minimize the risk of late effects. Radiographically involved lymph nodes should be included in the treatment ports. Metastasis sites should be treated with generous margins. [4]

Patient life expectancy should be taken into account when designing treatment ports. End stage disease should be treated with large fields and rapid fractionation. Infants with Stage 4S disease have a very good prognosis and should be treated with normal tissue sparing to avoid late effects. [4]

Doses necessary to control the tumor may be age dependent and debatable. 0-12 months: 9-12 Gy to gross residual disease 13-30 months: 24 Gy to gross residual disease 18 Gy to microscopic/subclinical disease 31-48 months: 30 Gy to gross residual disease 24 Gy to microscopic/subclinical disease 48 + months: 36 Gy to gross residual disease 30 Gy to microscopic/subclinical disease [1] || Brain: 60 Brainstem: 60 Liver: 50 Lung: 45 Kidney: 50 Lens: 10 Optic chiasm: 50 Optic nerve: 50 Retina: 45 || [2] Hoppe TR, Phillips LT, Roach M. //Leibel and Phillips Textbook of Radiation Oncology//. 3rd Edition. Philadelphia, PA: Elsevier; 2010. [3] Tokiwa K, Nakamura K, Ogita S, et al. Lymphatic drainage of adrenal neuroblastoma. //Journal of Pediatric Surgery.// 1993; 28(7):927-929. [4] The Use of Normal Tissue Tolerance Doses into Linear Quadratic Equation to Estimate Normal Tissue Complication Probability. Sanchez Cancer Center. http://www.rooj.com/Radiation%20Tissue%20Tolerance.htm. Accessed June 30, 2012. || Back to Week 6
 * **TD 5/5:** || Depend on location of tumor: [4]
 * **References:** || [1] Chao C. //Radiation Oncology Management Decisions.// 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2002.