Stage IV Thoracic Neuroblastoma (Morning Report)

Hem/Onc Morning Report

Hem/Onc Morning Report

Yohaimi Cosme-Ayala, MDArun Joseph, MDAmr Morsi, MD

Yohaimi Cosme-Ayala, MDArun Joseph, MDAmr Morsi, MD

History of Present Illness

• 3-years old Hispanic male with no previous medical history.

• Seen in Juarez multiple times and treated for pneumonia.

• Subjective weight loss, noted by wearing shorter-sized wardrobes. Previously active child, now cruising.

• Patient was readmitted in Juarez one week prior. CXR, Chest CT scan and laboratory findings were abnormal.

• Patient was admitted from the ED to hem/onc unit for further evaluation.

“low-grade fever, weight loss, chest and b/l leg pain x 3 mos”

Past Birth History

Social History

Surgical History

• Born in El Paso, full term with no complications.

• No known family history, unremarkable for malignancies.

• No previous surgeries

• Patient lives with both parents and older sibling (9-year old)

• Mother currently s/p C-section 5 days ago

Past Family History

Immunizations• Up to date (1-year immunization)

.Physical Exam

• General: Patient irritable on assessment, pale appearance.

• HEENT: b/l proptosis L>R, inability to close left eye completely, b/l temporal wasting, PERRLA, TM clear b/l, mild nasal congestion, moist mucosa, no LAD.

• Chest: right posterior chest dullness to percussion, as well as pain ipsilateral. Lungs clear to auscultation b/l.

• CVS: Tachycardic, RRR, no murmurs, capillary refill 2-3 secs.

• Abdomen: soft, NT/ND, no organomegaly, BS (+).

• Neuro: Alert and active, cruising, No other gross motor abnormalities observed, DTR (+) b/l lower extremities.

Length = 88cms

(5th percentile)

Wt = 11 kgs (<3rd

percentile)

Weight by length (<3rd percentile)

BP = 116/82mmHg

P = 142/minRR=40/minTemp = 36.6degC

What are your differentials at this point?

What would you like to do?

10.9

9.6

28.6

378

106

4.6

137

24

8

0.20

8.6

83

Segs 49.1%

Lymph 38.9%

Mono 10.6%

Eos 0.6%

Baso 0.7%

ANC 5400

HVA 262mg/g

VMA 202.9 mg/g

Uric Acid 2.7 mg/dl

PT 14.8

PTT 30.1INR 1.1Fibrinogen 252

U/A neg

U/Cx neg

Blood Cx neg

Sed Rate 116

Remember this CXR?

Remember the B/L

Proptosis?

.MIBG

1. Extensive and diffuse metastatic lesions throughout the skeleton.2. Large mediastinal mass.3. Homogeneous uptake in the liver without definite visualization of hepatic metastases.

Percutaneous Biopsy• Presence of round blue cells.

Poorly differentiated NeuroblastomaB/L Bone Marrow

Smear• Presence of round blue cells. Poorly differentiated Neuroblastoma

Hospital Course

A) Hematology-OncologyInitial workup : 7/01/14

MRI of Brain, MRI of Cervical region,MRI of Thorax ,MRI of Abdomen MRI of Pelvis MRI of thoracic and lumbar spine

Heme-Onc Course contd…

• Imaging, BM and percutaneous biopsy confirmed Stage 4 Neuroblastoma .

• Induction chemotherapy treatment initiated on 07/03/2014 under the ANBL0532 protocol.

• Administered cyclophosphamide and topotecan for 5 days.

• Neupogen 60mcg subcutaneously daily for the rest of the stay.

Heme-Onc Course contd…• received PRBCs x3 for H&H below 7 and 20 • platelets x1 on 07/14/2014 for platelet level of

14,000.

• Continued to be pancytopenic, but counts improved on a daily basis. CBCs with differentials obtained daily.

• Last CBC prior to discharge with a white blood cell count of 1800 (nadir 100), H and H of 10.1 and 29.8, platelets of 51, and ANC of 638 (nadir 0) .

B) Fluids and Nutrition• was placed on D5 ½ NS running initially at maintenance

• Increased to 1.5 ml/hr to prevent tumor lysis syndrome.

• Provided a regular diet, but due to his malnutrition state and failure to thrive, supplementation with Boost Kid Essentials /PediaSure following Pediatric Nutritionist consult.

• Interest in po feeds increased gradually • Megace (megesterol) 40 mg b.i.d. was started on

07/16/2014• Po intake increased significantly and at discharge, he

was consuming approx 75% of regular feeds.

C) Infections• Had febrile episodes on D3 & D5• Blood cultures were drawn following

episodes, but remained negative throughout his hospital course.

• Cefepime 50 mg/kg q8H started DOA 3• Vancomycin 20 mg/kg q6H initiated on DOA

5• remained afebrile for 14 days • antibiotics were discontinued on 07/18

(DOA 19) due to adequate increase in absolute neutrophil count and negative blood cultures.

D) Neurological• Parents reported ‘staring spells’ while patient was

febrile, on D1&2, but no seizure-like activity

• EEG show abnormal recording showing generalized asynchronous high-voltage spike and wave bursts.

• Neurology consult Dr. Fierro-Stevens: Based on assessment and history, no concerns for seizure-like activity. Recommended monitoring and follow up as needed.

• normal BAER prior to initiation of chemotherapy

E) Respiratory

• Had occasional mild intermittent coughing.

• Repeat CXR showed unchanged findings

F) Cardiac & Vascular• CVS unaffected during present stay.• Prior to chemotherapy treatment, baseline

echocardiogram was ordered • ECHO small PFO with L R shunting, but

with structurally normal heart. • On 07/02/2014, a Port-A-Cath was placed in

the left subclavian vein

G) Social

• Born in the USA, but no insurance.

• Mom 38 weeks pregnant at the time of admission, now s/p c-section POD #5.

• Issues with cord blood collection.

Discharge (7/18/14)• regular diet with PediaSure • Megace 60 mg b.i.d.• advised to wear mask outdoors, specially when

exposed to multiple people.• Port-A-Cath care with weekly assessments and

flushes.• Continue with Neupogen 60 mcg daily until

07/22/2014. • weekly CBC count as well cycle 2 induction on

07/24/2014.

ABP Content Specifications

• Recognize clinical findings associated with neuroblastoma.

• Plan the appropriate diagnostic evaluation of neuroblastoma.

General Considerations

• Neuroblastoma arises from neural crest tissue of the sympathetic ganglia or adrenal medulla.

• = Small round blue (hyperchromatic) cells.

• DDX small round blue: Ewings Sarcoma, Rhabdomyosarcoma, Peripheral Neuroectodermal tumors, lymphoma.

General Considerations

• Neuroblastoma accounts for 7-10% of pediatric malignancies.

• Most common solid neoplasm outside the CNS.

• 50% diagnosed before 2 years and 90% before 5 years of age.

Clinical Findings

• Presentation varies with primary site of the disease, neuroendocrine function of the tumor & metastatic effects.

• Constitutional symptoms are common including fever, weight loss and irritability.

• Bone pain is suggestive of metastatic disease (60 % in > 1 years of age)

Neuroblastoma should be considered in the differential diagnosis of children who present with:

• Abdominal mass (retroperitoneal or hepatic)• Abdominal pain or constipation• Proptosis• Periorbital ecchymoses ("raccoon eyes")• Horner syndrome (miosis, ptosis, anhidrosis)• Paraspinal mass• Localized back pain, weakness• Scoliosis, bladder dysfunction• Palpable nontender subcutaneous nodules• Opsoclonus myoclonus ataxia syndrome• Otherwise unexplained secretory diarrhea

Predilection to skull esp sphenoid & retroorbital

Bluish in color associated with erythematous flush followed by blanching

when compressed.

Diagnosis• Definitive diagnosis of neuroblastoma must be

made by:

– Histologic confirmation. – Evidence of metastases to bone marrow.

– Concomitant elevation of catecholamines in the urine.

Work Up• The minimal recommended evaluation for primary disease

should include CT or MRI scan of the primary site with three-dimensional measurements and MIBG scan if available, plus the following :

– Bilateral iliac crest bone marrow aspirate and biopsy.

– Technetium radionuclide bone scan plus plain radiographs for certain patients, especially those with MIBG nonavid tumors.

– Chest, pelvic and abdominal imaging by CT or MRI scan with three-dimensional measurements.

Prognostic Factors• Key factors influencing the clinical behavior of

neuroblastomas include tumor stage, age at diagnosis, pathologic risk classification, cytogenetics, and molecular genetics.

• These factors have been combined to define low-, intermediate-, and high-risk groups, which are used to define treatment strategies 

Prognostic Factors• Age

– Younger children (under 12-18 months) are more likely to be cured than older children.

• Tumor histology– favorable histology (differentiated)

– unfavorable histology (undifferentiated)• MYCN gene amplifications

– A reliable marker of aggressive behavior and rapid disease progression.

Prognostic Factors• DNA ploidy in infants:

– same amount of DNA as normal cells (a DNA index of 1) are classified as diploid

– Cells with increased amounts of DNA (a DNA index higher than 1) are termed hyperdiploid.

– hyperdiploid cells tend to be associated with earlier stages of disease, respond better to chemotherapy, and usually predict a more favorable prognosis (outcome) than diploid cells.

– Not useful in older children.

Prognostic Factors• Chromosome deletions:

– 1p deletions or 11q deletions may predict a less favorable prognosis. It is thought that these chromosome parts, which are missing in many neuroblastomas, may contain important tumor suppressor genes.

Staging Systems• International Neuroblastoma Staging System (INSS).

(site + uses the results of surgery to help define the stage

• International Neuroblastoma Risk Group Staging System. (INRGSS) (doesn’t use the results of surgery to help define the stage)

Staging Systems

Neuroblastoma risk groups • Children’s Oncology Group (COG) risk

groups.

• International Neuroblastoma Risk Group (INRG) classification.

Children’s Oncology Group (COG) risk groups

International Neuroblastoma Risk Group (INRG) classification.

Survival rates• Survival by Children’s Oncology Group (COG) risk

group

– Low-risk group: Children in the low-risk group have a 5-year survival rate that is higher than 95%.

– Intermediate-risk group: In children in the

intermediate-risk group, the 5-year survival rate is around 90% to 95%.

– High-risk group: The 5-year survival rate in children in the high-risk group is around 40% to 50%.

Treatment• For children with low-risk disease

– surgery is the primary treatment modality when complete resection is feasible, with several exceptions.

– For patients with low-risk tumors that cannot be completely resected or which have life-threatening complications, chemotherapy and/or radiation therapy may be required.

• In the subset of patients with asymptomatic 4S disease, observation may be an option, since there is a high rate of spontaneous regression.

• For infants younger than six months of age with small, localized adrenal masses, expectant observation with serial ultrasound and urine catecholamines.

Treatment• For children with intermediate-risk disease, a

combined modality approach that includes chemotherapy and surgical resection is standard. The degree of surgical resection required is under investigation. The role of radiation therapy is less clear, except in the context of disease progression despite chemotherapy plus surgery or for complications such as spinal cord compression.

• For children with high-risk neuroblastoma substantial improvements have been seen with aggressive combined modality approaches. These generally include chemotherapy, surgical resection, high dose chemotherapy with stem cell rescue, radiation therapy and biologic/immunologic therapy. This approach has improved event free survival, but the majority of patients eventually relapse and die of their disease.

FINAL DIAGNOSIS

Stage IV Neuroblastoma