1. Pediatric Oncology for the Primary Care Provider Kate A
Pediatric Oncology for the Primary Care Provider Kate A. Mazur, MSN, RN, CPNP Texas Children’s Hospital Advanced Practice Provider 1st Annual Conference Houston, TX February 8, 2014

2. Objectives Review the incidence of childhood cancer
Describe the most common childhood malignancies, with a focus on initial evaluation and diagnosis, red flags, and when to refer to specialist
Analyze the unique precautions for patients with oncologic illnesses
Through out the presentation, you’ll notice some text highlighted in red – these are the items that can be considered “red flags” or important take home points to help you to know when to refer to oncology
Long term survivorship issues are hugely important for PCPs but earlier this conference Dr. ZoAnn Dreyer did an excellent presentation on this issue so I will not discuss it in this talk
And I will also not talk about any treatment for this presentation b/c I think it’s beyond the scope of this talk and the treatment is usually managed by the oncology team and followed closely by them throughout the course of treatment

3. The Scope of the Problem
13,400 children ages birth to 19 years are diagnosed with cancer each year
Cancer is the #1 cause of disease-related death in children
Source: Surveillance, Epidemiology, and End Results Program, , Div. of Cancer Control and Pop. Sciences, NCI, 2006

4. The Good News…
Overall 5 year survival rate across all cancers is now 80%
Estimated 270,000 childhood cancer survivors in the U.S.
However, two-thirds of survivors face at least one chronic health problem
25% of survivors face a late effect from treatment that is classified as severe or life- threatening
I left this slide in here even though Dr. Dreyer presented survivorship in more detail but I think this is just very important to drive home. These children are being seen out in the community both before and after diagnosis into long term survivorship
it is imperative that all survivors of childhood cancer receive ongoing monitoring and continued physical and psychosocial care throughout childhood, adolescences, and into their adult lives

5. Where do I start?
Early diagnosis and initiation of treatment is imperative to improved survival
Diagnosis of cancer starts with a thorough history and physical
Most symptoms of childhood cancer due to either a mass, its effect on the surrounding tissues, invasion of the bone marrow, or secretion of a substance by the tumor that disturbs normal functions
Most common presenting signs and symptoms of many malignancies include weight loss, failure to thrive, anorexia, malaise, fever, pallor, and lymphadenopathy
Chief complaint is the most important clue

6. High Risk Patients Familial cancer pre-disposition syndromes
Li-Fraumeni Syndrome
Familial adenomatosis polyposis
Beckwith-Wiedemann Syndrome
Family history of cancer
Retinoblastoma
Autoimmune diseases in patient or family
Down Syndrome
Neurofibromatosis Type 1
HIV/AIDS
> 50 familial cancer predisposition syndromes have been described
Li-Fraumeni – p53 mutation; breast CA, soft tissue sarcoma, osteosarcoma, leukemia, brain tumors, ACC, and others
FAP – APC gene; both benign and cancerous tumors in small intestine, brain, stomach, bone, skin, and other tissues
BWS – Wilm’s tumor, pancreatoblastoma, hepatoblastoma
RB – RB1 gene; any eye cancers, CA of pineal gland, osteosarcoma, melanoma, and soft tissue sarcoma
Autoimmune – bigger risk factor in adults; lymphoma, Cancers caused by viruses (cervical CA, liver CA, stomach CA)
Downs – increased risk ALL
NF-1 – chromosome 17 mutation; peripheral nerve sheath tumors
HIV – non-Hodgkin lymphoma, Kaposi sarcoma

7. Leukemia Cancer of the bone marrow
Uncontrolled proliferation of immature white blood cells (“blasts”)
Most common type of cancer in children and adolescents under 20 years of age (~30%)
Incidence
4900 new cases each year
Males > Females; Hispanics > Caucasians > African Americans
Peak age 2-5 years
Risk factors
Down Syndrome: 14-fold increase
Klinefelter Syndrome
Fanconi anemia
Immunodeficiencies: ataxia telangiectasia, Wiskott-Aldrich, Bloom syndrome
Past exposure to chemotherapy or ionizing radiation
Immature WBCs, such as myeloblasts, lymphoblasts, and monoblasts
Does appear to be a race difference
Note that none of these slides will list “causes” b/c the cause of the majority of childhood cancers is still unknown. I have listed some risk factors if any have been identified that may increase your risk of developing that particular malignancy
Klinefelter syndrome – extra “X” chromosome; slight increase
Fanconi anemia – genetic defect in cluster of proteins responsible for DNA repair
Immunodeficiencies: r/t increased risk of infection
Ionizing radiation is the ONLY environmental factor that has been proven to play a role in the development of childhood ALL. Lots of false information out there re. pesticides, etc; constantly being studied. Discovery of the link to ionizing radiation was made following the atomic bombs in Japan, where children who were exposed acquired an increased risk of developing leukemia.
Leukemia almost certainly caused by some sort of virus or other infection, but has not been identified yet. Due to age at presentation (early school aged)

8. Most Common Types of Childhood Leukemia
Acute lymphoblastic leukemia (ALL) ~ 80%
Acute myelogenous leukemia (AML) ~ 15%
Chronic myelogenous leukemia (CML) ~ 5%
Each main type of leukemia is named for the type of cell that is affected (a myeloid cell or a lymphoid cell) and whether the disease begins in mature or immature cells

9. Leukemia: Presenting Signs and Symptoms
Relate to the infiltration of the bone marrow
History
Fatigue
Persistent fevers
Bone pain
Anorexia
Weight loss
Recurrent infections
Physical Exam
Pallor
Bleeding, bruising, or petechiae
Hepatosplenomegaly
Lymphadenopathy
Most of the presenting signs and symptoms relate to the abnormal blood counts
May present with a limp or refusal to bear weight
Recurrent infections – have a high index of suspicion for the kid that frequently returns with ear infections, for example
Frequent nose bleeds; gingival bleeding when brushing teeth, etc
HSM might cause abdominal distension

10. Lymphadenopathy: When to Worry
Supraclavicular, axillary, or epitrochlear adenopathy
Adenopathy that persists longer than 6 weeks or is increasing in size
Asymmetric lymphadenopathy
Leukemia usually presents with generalized lymphadenopathy; localized LAD more likely to be infectious in origin
Malignant nodes generally hard and nontender; infectious/inflammatory nodes usually tender, freely moveable, overlying erythema
For localized cervical adenitis with inflammation and fever, treat with ONE course of antibiotics, if no response  refer
DO NOT START STEROIDS
I cannot stress this enough. It will muddy the clinical picture and ultimately cause a delay in the accurate diagnosis and treatment start

11. Leukemia: Initial Diagnostic Tests
CBC with manual differential, reticulocyte count, and peripheral blood smear
Chem 10: Electrolytes, BUN, creatinine, Ca2+, Mg2+, PO4-, uric acid, LDH
Hypocalcemia, hyperkalemia, hyperphosphatemia, hyperuricemia may indicate tumor lysis syndrome  oncologic emergency
Elevated LDH (non-specific tumor marker)
Bone marrow aspirate and biopsy is the only definitive diagnostic test
Done by oncology service only
Specify you want the differential on the order b/c this is not automatically done at all labs. Also, most labs do an automatic diff and often do not do a smear, so if the initial CBC is concerning, you may want to send a second sample to an alternative lab, such as at a larger hospital-based lab where you can get all of these components
I’m going to review the CBC findings in the next few slides
These electrolyte abnormalities may be indicative of tumor lysis syndrome which is an oncologic emergency. I won’t go into detail on this since TLS was covered by Brooke Bernhardt in the pharmacology pre-conference but if you see this, you need to either call the oncology team immediately or send the patient to the ER
LDH is an indicator of tissue breakdown; cancer cells in general have a very high turnover rate so the destroyed cells lead to an elevation in the LDH
LP if no contraindications such as elevated ICP (risk for herniation)
BMA and LP ONLY to be done by the oncology service after referral
~5% of leukemia pts have CNS involvement at presentation

12. Complete Blood Count: A Review
White blood cells/Neutrophils
Responsible for fighting infection
Red blood cells/Hemoglobin
Carries O2 from lungs to blood tissues and CO2 from tissue to lungs
Platelets
Necessary for clotting and control of bleeding
Most important screening tool for leukemia that is easy to obtain, relatively non-invasive, inexpensive, and can be done in an outpatient primary care setting
Cannot understand leukemia without first understanding the basics of the CBC components and what is normal in order to identify when to be concerned for malignancy

13. CBC Findings in Leukemia
Leukocytosis - ~50% with WBC >10,000 and ~20% > 50,000
Elevated blasts and low neutrophils
Anemia
Thrombocytopenia
2 or more cell lines decreased  REFER
90% present with hemoglobin < 11g/dL, 45% < 7g/dL
75% present with platelets < 100,000/mm3
CBC is the most important screening tool for PCPs and can give you 90% of the information you need for the diagnosis

14. Lymphoma Tumor of the lymphatic system Incidence Risk factors
1500 new cases each year
More common in adolescents and older teenagers, males, Caucasians
Risk factors
Immunodeficiency syndromes: Wiskott Aldrich, SCIDS, HIV/AIDS
Autoimmune diseases: RA, SLE
Some viruses: Epstein-Barr (particularly for Burkitt’s lymphoma)
Since lymphoma is a cancer of the lymphatic system, which is responsible for defending the body from foreign invaders, most of the predisposing risk factors have to do with disorders that affect the immune system, either under-active (as is the case in ID or over-active as in AI)
Wiskott Aldrich – X-linked, recessive disease; chronic thrombocytopenia, recurrent infections
SCIDS – severe combined immunodeficiency syndrome; absence of functional T-lymphocytes
HIV/AIDS – HIV pts are determined to have AIDS when they develop significant conditions and/or diseases in conjunction with the virus and often lymphoma is this determining factor
Large correlation b/w autoimmune diseases and lymphoma – b/c as you know, in autoimmune disorders, the immune system sees its own tissues and attacks them as it would a germ or foreign invader. Lymphocytes (the cells from which lymphomas start) are part of the body’s immune system so the overactive immune system in autoimmune disorders may cause lymphocytes to grow and divide more often than normal and increase the risk of them developing into lymphoma cells
Some viruses directly affect the DNA of lymphocytes, helping to transform them into cancer cells
EBV – member of the herpes virus family, extremely common, responsible for mono infections and most cases of EBV are not serious. However, in pts w/compromised immune systems (i.e. HIV or AIDS) in which T-cells do not destroy infected B-cells, EBV-infected cells may become cancerous. Strongest correlation b/w EBV and lymphoma pertains to Burkitt’s lymphoma

15. Types of Lymphoma Non-Hodgkin’s Lymphoma – 60%
Lymphoblastic
Anaplastic
Burkitt’s
Diffuse large B-cell
Hodgkin’s Lymphoma – 40%

16. Lymphoma: Presenting Signs and Symptoms
History – 75% asymptomatic
Unexplained fever for more than 3 days
Weight loss of 10% within 6 months
Drenching night sweats
Malaise
Anorexia
Physical Exam – based on location of disease
Head/Neck: supraclavicular or cervical adenopathy, jaw swelling, unilateral tonsillar enlargement
Abdomen: splenomegaly, abdominal distention, jaundice
Mediastinum: cough, chest pain, stridor
Again, similar to leukemia, the lymph nodes are usually firm and are often described as “rubbery”. May be painless or painful if it has enlarged quickly

17. Lymphoma: Evaluation and Diagnostic Work Up
DO NOT START STEROIDS
Blood work: CBC w/diff, liver and renal fxn tests, including alkaline phosphatase; ESR, ferritin, LDH may be elevated
Imaging Studies
CT scans (neck, chest, abdomen, pelvis)
PET scan
Bone scan
Biopsy of affected node
Required for definitive diagnosis
Done under guidance of oncology team only
CBC – might see cytopenias if there is bone marrow disease
ESR, ferritin, LDH – non-specific, indicators of inflammation and cell turnover
although XR can be performed quickly to determine presence of mediastinal mass, it won’t give you much other information about the extent of disease
CT to evaluate for metastasis
Positron emission tomography – only 70% of pts have disease that will show up on a PET scan. This is a nuclear imaging scan, where they inject a dye before the scan and it gets taken up by the malignancy which will then show up as a bright spot on the scan. However, the dye can also be taken up by infection or thrombosis so you may get false positives. So it’s really helpful to use the two imaging techniques in conjunction with one another to get the most information possible.
Sometimes a bone scan is done if there is bone pain, an elevated alkaline phosphatase, or suspicion for metastatic disease but this may not be done with every patient
Biopsy – only oncology service should perform this procedure

18. Brain Tumors Can be malignant or “benign”
Much slower rate of treatment advances than other malignancies
Unique challenges in children – brain still developing
Incidence
3400 new cases every year
More common in ages < 15 years
Risk factors
Little known
Hereditary cancer predisposition syndromes (i.e. Li-Fraumeni Syndrome)
I use quotes around benign, b/c this term isn’t really helpful in pediatric oncology and rarely used. This is b/c even the most low grade tumors can have devastating effects b/c of the nature of its location
Brain is immature – much more likely to result in devastating late effects with huge morbidity associated with treatments for brain tumors, with the biggest player being radiation to the brain and what that can do later down the road to things like cognition, growth and development, hormones, etc

19. Most Common CNS Tumors Astrocytoma Brain Stem Glioma Medulloblastoma
Most supratentorial
but can originate in
cerebellum, brainstem,
or hypothalamus
Brain Stem Glioma
Medulla, pons
Medulloblastoma
Cerebellum
Ependymoma
Ependymal tissue within the ventricular system,
most commonly the fourth ventricle
Astrocytoma – originate in astrocyte cells
BSG – diffuse, infiltrating, very poor survival
Medulloblastoma – highly cellular; arises from primitive neuroepithelial cells
Ependymoma – predominantly arise from epithelial cells lining the ventricles in the brain
Picture from The Children’s Hospital at Montefiore,

20. CNS Tumors: Presenting Signs and Symptoms
Depends on site and severity of disease as well as child’s age & development
History
Seizures
Visual changes
Headache
Nausea/vomiting, often in morning
Poor concentration or mental status change
Physical Exam
Hemiparesis
Endocrinopathies
Ataxia
Cranial nerve deficits
signs of increased ICP
lethargy, academic changes, personality changes

21. Headache: When Further Evaluation is Warranted
Recurrent morning headache
Headache that awakens the child
Intense, incapacitating headache
Changes in the quality, frequency, or pattern of headaches
Presence or onset of neurologic abnormality
Ocular findings such as papilledema, decreased visual acuity, or loss of vision
Associated with vomiting that is persistent, increasing in frequency, or preceded by recurrent headaches
Age 3 years or less
DO NOT START STEROIDS
increased severity, increased frequency
children this young don’t usually complain of headaches
these findings might suggest the need for a CT scan – do not wait until you can schedule one a few weeks down the road. Send to the ER to get one same day if you have a high index of suspicion for CNS pathology

22. CNS Tumors: Diagnostic Tests
Imaging studies are the only diagnostic tests
MRI brain and spine
CT often obtained first due to easy access
LP if clinically
indicated and safe
to perform
on the left – medulloblastoma
as you can see, these aren’t always a solid mass. They can just appear as a sort of brightening, or what we call “enhancement”. The one on the right is more diffuse, that one on the left is more of a solid mass; sometimes you see a darkening in the center that usually represents some necrotic tissue. Sometimes if tumors grow really rapidly, then the tumor cells in the center might start to die as new ones form.
Some CNS tumors have the potential to seed along the CSF pathway, so CSF cytology should be tested in patients with tumors such as medulloblastoma or ependymoma. However, and this is important – you MUST do the MRI BEFORE the LP to make sure it is safe to perform the procedure. If the MRI shows any evidence of midline shift on it, then there is a risk of herniation during the procedure and it must not be performed

23. Solid Tumors: Evaluation of an Abdominal Mass
ALWAYS suspect a malignant solid tumor in a child with a palpable abdominal mass
Avoid abdominal palpation as much as possible; palpate gently if necessary
In younger children, often renal  neuroblastoma or Wilms’ tumor
In older patients, may be related to leukemia or lymphoma with enlargement of the spleen or liver
Obtain comprehensive GU and GI histories
Associated symptoms of flushing, palpitations, diarrhea, failure to thrive, and fever could point to disseminated process such as neuroblastoma
Complete exam with focus on skin, extremities (bone pain), neuro exam (Horner’s syndrome, spinal cord compression), organomegaly, measurement of abdominal girth
Obtain diagnostic imaging STAT
Usually start with abdominal ultrasound
Newborns might be an exception to this. I would still have malignancy on your list of differentials, but an abdominal mass in a neonate is usually renal in origin and most commonly caused by hydronephrosis or multicystic kidney
Once you have either felt the initial mass on your exam or if it is obvious just by looking at the patient (i.e. abdominal distention, prominent veins), then do not palpate the abdomen. This is also not the time for you to have every med student or resident come and feel the abdomen. If there is a malignancy, it could be encapsulated and pressing on it might break open the capsule, causing the tumor cells to spill out and spread all over the body
Other possible malignant causes include rhabdomyosarcoma, rhabdoid tumor, hepatoblastoma, sarcomas, or an ovarian tumor
Do not wait until the next available outpatient scan date that is a few weeks down the road. Send them to the ER if you have to.
Imaging can include a plain film of the abdomen, chest XR, abdominal ultrasound, CT scan (include chest and pelvis in addition to abdomen), bone scan, MRI spine if neuro symptoms

24. Wilm’s Tumor Large, rapidly growing, vascular renal tumor
Second most common intra-abdominal malignancy in children
Can be bilateral or unilateral
Incidence
500 new cases/year
Peak incidence 3 years of age
Slight female predominance; African-Americans > Caucasians > Asians
Risk factors
Congenital anomalies: GU malformations, hemihypertrophy, Beckwith-Wiedemann syndrome, Denys-Drash syndrome
Familial pre-disposition syndromes: Li-Fraumeni syndrome
In the interest of time, I am only going to review the most common solid tumors of childhood
BWS – an overgrowth syndrome
Denys-Drash – involving genitourinary abnormalities

25. Wilm’s Tumor: History and PE Findings
Abdominal mass – smooth, firm, rarely crosses midline but 5- 10% are bilateral
Diffuse abdominal distention with large masses
Usually asymptomatic, but 25% have abdominal pain, vomiting, hematuria, hypertension
Signs of thrombosis: leg swelling, prominent veins over abdomen
Signs of hemorrhage into tumor (occurs rarely): anemia, fever, rapid abdominal distension
parents are often the first ones to notice the abdominal mass or distension
thrombosis occurs more often than hemorrhage

26. Wilm’s Tumor: Diagnostic Tests
Blood work – CBC, liver function, renal function
Coagulation screen – may acquire Von Willebrand’s
Abdominal ultrasound usually first test ordered – will reveal mass arising from within kidney
Doppler US to assess patency of renal vein and inferior vena cava
Abdominal CT
There are no specific tumor markers for wilms, but initial blood work might consist of CBC, LFTs, renal function may be impaired, however, it is often normal
studies have shown that as many as 8& of Wilms’ tumors pts develop Von Willebrand’s disease at diagnosis; so this should be evaluated for to determine whether treatment with DDAVP is necessary to correct coagulation prior to surgical intervention
Doppler US b/c thrombosis can occur
Abdominal CT further assesses the extent of the mass and can assess for smaller lesions in the contralateral kidney; can also assess for any liver metastases

27. Neuroblastoma
Cancer of the sympathetic nervous system; derived from neural crest cells
Second most common solid tumor of childhood and the most common extracranial solid tumor
Incidence
650 new cases every year in the U.S.
90% cases in children < 5 years old
Boys > girls; Caucasian predominance
Risk factors
Most cases sporadic
Has been identified in other disorders of neural crest cells
Neurofibromatosis
Hirschsprung’s disease
Beckwith-Wiedemann syndrome
DiGeorge syndrome
Neural crest cells are the cells that make up the sympathetic or peripheral nervous system that can grow in the sympathetic ganglia, adrenal medulla, among other sites
median age is 2 years so these pts are somewhat younger than Wilms’ tumor patients

28. Neuroblastoma: Clinical Presentation
Can arise anywhere along sympathetic nervous system
Signs and symptoms depend on location of primary tumor and presence of metastasis
Two-thirds have primary site in abdomen, usually adrenal
Thoracic region is the next most common primary site
About 60% have metastatic disease at presentation due to vague initial symptoms and late presentation
Bone marrow
Bone
Liver
Skin
Orbits
these kids appear more ill than the Wilms’ tumor patients due to the high incidence of metastatic disease at diagnosis

29. Neuroblastoma: Presenting Signs and Symptoms
Firm, irregular, non-tender abdominal mass
Hepatomegaly
Abdominal pain
Urinary obstructions
Flushing
Sweating
Diarrhea
Anorexia
Malaise
Site-specific symptoms from metastases to bone, skin, liver, or CNS
Opsoclonus-myoclonus syndrome – “dancing eyes and dancing feet”
I’m only going to review the s/s related to the most common locations of primary disease and metastatic disease
neuroblastoma is one of the few causes of massive hepatomegaly
flushing, sweating, diarrhea are related to tumor secretion of vasoactive instestinal peptide
Bone – bone pain, limp
Skin – blueberry muffin lesions which i’ll show you a picture of in an upcoming slide
Liver – jaundice
CNS – seizures, neuro s/s, cranial nerve deficits
Horner’s syndrome – ptosis of the eyelid; meiosis=constriction of the pupil on the same side; anhidrosis=decreased sweating on that side of the face (sometimes parents will report that only one side of their face gets red when they are outside or have been running; it would be the unaffected side)
opsoclonus-myclonus – consists of myoclonic jerks, ataxia, and jerky eye movements and is a unique paraneoplastic syndrome associated with neuroblastoma. If you see this, it should prompt a search for an occult neuroblastoma even in the absence of an abdominal mass

30. Neuroblastoma: Presenting Signs and Symptoms

31. Neuroblastoma: Diagnostic Tests
CBC – cytopenias
Chem 10
Ferritin, LDH, uric acid
Liver panel
Urine catecholamines (VMA/HVA)
CT chest/abdomen/pelvis
Tissue biopsy for definitive diagnosis
Bilateral bone marrow aspirate and biopsy to evaluate for BM involvement
MIBG scan or bone scan to evaluate for metastasis
ferritin, LDH, uric acid may all be increased, although these are very non-specific tests; increased in many cancers but also in non-malignant causes, just markers of inflammation and high cell turnover
these tumors excrete catecholamines so these are elevated in about 90% of cases; these are used as screening techniques in the past, but abdominal ultrasound or CT is the current diagnostic procedure of choice

32. MIBG Scan
as you can see, these can be very hard to read. An MIBG scan is another nuclear medicine technique just like the PET scan I talked about earlier. A dye is injected before the scan that will be taken up by catecholaminergic cells and areas of disease will then show up as bright spots on the scan. However, there are also some spots that always light up which is why additional scans are often needed and the MIBG is primarily used to evaluate the extent of disease and look for metastasis. You’ll see normal uptake in the salivary glands, myocardium, liver, and bladder

33. Osteosarcoma Tumor of the bone; usually at the end of long bones
Incidence
400 new cases/year
More prominent during adolescent growth spurt; periods of rapid bone growth
Males > females; African-Americans > Caucasians
Risk factors
Ionizing radiation
Hereditary retinoblastoma
Li-Fraumeni Syndrome

34. Osteosarcoma: Signs and Symptoms
Dull, aching pain, usually worse at night
+/- soft tissue swelling, warmth
May have vascularity over the mass
Decreased range of motion
Often long duration of symptoms prior to diagnosis; can be up to 6 months

35. Osteosarcoma: Diagnostic Tests
Diagnostic Imaging
Plain radiograph of affected area – “sunburst
pattern”
MRI to further examine tumor boundaries, soft
tissue component, relationship to joints, blood
vessels, neurovascular bundle
Chest XR or CT to evaluate for mets
Bone scan to evaluate for skeletal mets
Blood Tests
Elevations in LDH, alk phos may be present
Tumor Biopsy
Necessary for definitive diagnosis
Lungs are most common site of metastasis; XR is a lot faster, cheaper, easier to get than a CT but a CT is more sensitive for smaller pulmonary nodules that an XR might miss
Again, there are no specific tumor markers for osteosarcoma and the LDH and alk phos aren’t tumor-specific; abnormalities do not distinguish b/w bone and liver etiologies

36. Supportive Care of a Patient with Cancer Infection Prophylaxis
Good hand washing!!
Proper dental hygiene – daily brushing with a soft brush, use of chlorhexidine mouth rinse
Avoidance of crowded, enclosed spaces
Cleanliness of perirectal area – avoid constipation
No rectal temperatures!
Prophylaxis for Pneumocystis carinii pneumonia (PCP) from time of diagnosis until 6 months after completion of therapy – Trimethoprim- sulfamethoxazole, Pentamidine, Dapsone
Viral and fungal prophylaxis may be indicated
children receiving chemo are susceptible to acquiring infection from bacterial, viral, fungal, and protozoal organisms
They are chronically myelosuppressed, and at times, severely myelosuppressed, as a direct result of the chemotherapy and have an increased exposure to nosocomial organisms
many of these children have central venous catheters and may intermittently have mucosal breakdown secondary to chemo – 2 situations that interrupt the integrity of the physical defense barriers
hyponutrition also plays a significant role in host susceptibility
certain standards of care can be implemented to minimize the risk of acquiring serious infections in these childrens
Avoid constipation just means encouraging a proper diet and liberal use of stool softeners if necessary
and no rectal suppositories either; we want to avoid the possibility of a mucosal tear and entrance of enteric organisms
PCP is an opportunistic infection that can be acquired in immunocompromised hosts
Bactrim is usually first line. It is given twice daily on three consecutive days/week. Pentamidine is an inhaled or IV treatment, usually given monthly, that is used when patients can’t tolerate Bactrim or have a sulfa allergy. Dapsone can also be used, but this is falling out of favor b/c they have seen methemoglobinemia develop that has been linked to dapsone use just recently

37. Management of Fever in the Child with Cancer
Defined as a single temperature of ≥ 101°F or two temperatures ≥ °F taken 1 hour apart
Do not give anti-pyretics!
No rectal temperatures
Every cancer patient who presents with fever should be considered septic until proven otherwise
Prompt evaluation and management essential for improved survival
Goal is to administer first dose of IV antibiotics within 1 hour of presentation
you do not want to mask a fever b/c it is a sign that some sort of an infectious process is going on that we would want to be able to promptly recognize and treat
since their immune systems are not working properly, they may not have the same signs or symptoms of an infection as a normal host would, so fever may be the only sign of infection

38. Initial Evaluation of Fever
Prompt tx essential – send to ER or urgent care center for immediate evaluation and management and call oncology service
Evaluate for signs of septic shock
Tachycardia – usually the first sign of shock. Ideally, aggressive treatment starts here.
Check perfusion – delayed capillary refill; pulses weak and thready or bounding
Hypotension – LATE sign
Mental status changes; lethargy – OMINOUS
Examine for focal signs of infection
Often there are none
Oral cavity, perianal area, skin, respiratory tract, abdomen (typhlitis)
these kids can deteriorate VERY quickly. I cannot stress that enough. We have gotten very good at recognizing shock early and treating aggressively so often can avoid long ICU stays or starting pressors on these kids. A lot of things can cause tachycardia so many of us have started to disregard its significance. And many of those causes are reasons these pts could be tachycardic (anemia, anxiety, pain, fever) but now there is an evidence based table that corrects HR for fever and if the HR exceeds that number for the child’s age, we start treating them for shock. There are very few kids who will be harmed by fluid resuscitation or antibiotics. There are some exceptions, and those kids would be carefully considered and treatment modified accordingly. But the benefit far outweighs the risk.
I won’t go into the signs of septic shock since I believe Dr. Patel did a separate talk on this subject

39. Fever: Diagnostic Work Up
CBC with differential – risk-based management based on neutrophil count
Blood cultures – all CVC lumens and peripheral; important to have prior to first dose of antibiotics
Urinalysis/urine culture, if feasible based on clinical status – no catheterization
Additional cultures of any potential sources of infection – skin lesions, stool sample if diarrhea, mouth sores
Do NOT I & D any skin lesions
Chest XR if respiratory symptoms – obtain portable or delay until after initial antibiotics
Do NOT perform LP until oncology service is consulted
the overall theme is that we do not want to delay the start of antibiotics for these patients
if an LP seems indicated initially, contact the pediatric oncologist immediately for assessment. Evaluation for increased ICP may be necessary by imaging in some patients prior to lumbar puncture

40. Empiric Therapy of the Febrile Patient
DO NOT wait for culture results
Broad-spectrum antibiotics must be started immediately; will tailor antibiotic choice when culture results known
Antibiotics chosen based on individual institution’s local microbial prevalence and antibiotic susceptibility patterns
Regimen also based on risk criteria – high risk if ANC < 100, infant ALL, AML, in any phase of leukemia tx other than maintenance (induction at highest risk), < 7 days from last chemotherapy, focal signs of infection, or concern for sepsis
Admission often indicated
Anti-virals and/or anti-fungals may be added as clinically indicated
Septic shock treated aggressively with normal saline
fluid boluses and triple antibiotics
I’m going to skip this slide since this was covered in Brooke Bernhardt’s talk on oncologic emergencies
these patients will usually need more than one IV access so these interventions can be done simultaneously

41. Immunizations and the Cancer Patient
Cannot assume adequate immunization even if patient’s vaccines are up to date prior to diagnosis
NO LIVE VACCINES
Siblings or household contacts should not receive the oral polio vaccine
All other vaccines may continue as scheduled, but will need to check titers at completion of treatment to ensure adequate immunity. Boosters or full re-immunization may be needed after completion of therapy
Highly recommend seasonal influenza vaccination in patient and household contacts
this is b/c all the chemo they get wipes out their immune system. Assume they are susceptible to everything. This is why herd immunity is so important. To protect patients like this from getting a potentially devastating disease that their immune systems will not be able to handle
pts receiving chemotherapy or who are otherwise immune compromised, should not receive live virus vaccines – specifically the MMR and varicella vaccines. Also includes oral polio and the nasal spray formulation of the influenza vaccine (oral polio is a live vaccine; the injection is inactivated)
Oral polio vaccine is contraindicated in household contacts b/c viral shedding may occur for 8-12 weeks and may lead to paralytic poliomyelitis in an immunocompromised patient so inactivated polio vaccine should be given instead. All other vaccines are safe to be administered to household contacts, included the other live vaccines such as MMR and varicella b/c transmission of disease from these vaccines does not occur
may continue as scheduled, however, this sort of comes with a caveat – the inactivated vaccines pose no special risk to immunosuppressed children, but they pts may not respond adequately to the vaccine so we often hold all vaccines until therapy is completed with the exception of the flu vaccine!
whether immunization occurred prior to or during chemotherapy since there is the potential loss of protective antibody titers as the result of immune suppressive therapy

42. References
Howlader N. et al. SEER Cancer Statistics Review, , National Cancer Institute. Bethesda, MD, based on November 2012 SEER data submission, posted to the SEER web site, April 2013.
Hastings, C. (2002). The Children’s Hospital Oakland Hematology/Oncology Handbook. St. Louis, MO: Mosby, Inc.
Kline, N. & Tomlinson, D. (2005). Pediatric Oncology Nursing. Heidelberg, Germany: Springer Publishing.
Lowry, A., Bhakta, K., & Nag, P. (2011). Texas Children’s Hospital Handbook of Pediatrics and Neonatology. McGraw-Hill Publishing.
Pizzo, P. & Poplack, D. (2005). Principles and Practice of Pediatric Oncology, 5th edition. Philadelphia, PA: Lippincott, Williams & Wilkins.
Zorc, J. (2013). Clinical Handbook of Pediatrics, 5th edition. Philadelphia, PA: Lippincott, Williams & Wilkins.

43. Questions??