Pediatrics Flashcards

Question

Pediatric CNS tumors- Medulloblastoma -5

Answer 1

A primitive neuroectodermal tumor (PNET) Median age at diagnosis = 5-6 years Arises in cerebellum 25-45% have leptomeningeal mets at diagnosis Rapidly growing, so short duration of symptoms - BECAUSE OF THIS AMENABLE TO CHEMO

Answer 2

Early symptoms: signs and symptoms of increased ICP, headache, emesis, lethargy, hydrocephalus ``` Late symptoms : ataxia, diplopia, weakness, papilledema, strabismus ```

Answer 3

Favorable disease: 1. children older than 3 years of age, 2. localized disease that has complete or near total resection High risk: 1. invasive disease that limits total resection (greater than 1.5cm2 residual disease) 2. overt metastatic disease (subarachnoid seeding)

Answer 4

M0 = No gross subarachnoid or heme mets M1 Microscopic tumor cells in CSF M2 Gross nodular seeding in cerebellum, cerebral subarachnoid space, or in third or fourth ventricles M3 Gross nodular seeding in spinal subarachnoid space M4 Extraneuraxial metastasis

Answer 5

Surgery is KEY! Need complete or near complete resection. Can do post-op MRI to detect residual disease and operate a second time to improve resection. Bone marrow aspirate and biopsy (5% have systemic mets)

Answer 6

wonderful addition, but only if you are at least 3 years of age, IDEALLY OVER 5 YO Attempting to use chemo to decrease dose of XRT or avoid it altogether. inability to give XRT to younger kids hurts their chances of survival Some low risk patients can be cured with post-op radiation

Answer 7

NO SOC Cisplatin, vincristine, prednisone, cyclophosphamide, lomustine and topotecan have been used post-op. Chemo used to avoid XRT in very young (<3) Chemo can be used with XRT to decrease the dose of XRT used in low risk patients Unclear if chemo improves survival in low risk patients

Answer 8

#CVP lomustine (CCNU) 100mg/m2 po x 1 vincristine 1.5mg/m2 IV weekly x 3 prednisone 40mg/m2 po x 14 days #philadelphia regimen Cisplatin 90mg/m2 IV x 1 Lomustine 100mg/m2 PO x 1 Vincristine 1.5mg/m2 weekly x 3

Answer 9

metastatic stage M adjuvant treatment residual tumor

Answer 10

60-80% survival rate based on how aggressive surgery was as well as chemo, XRT ``` Poor risk: less than 3 years of age, subarachnoid seeding, greater than 1.5cm2 tumor remaining post-op, histology, diploid DNA content, C-myc amplification, deletion of 17p ```

Answer 11

``` #Most are slow growing (low grade): I and II #About 20% are malignant (anaplastic astrocytoma or glioblastoma) # 2 histologic types: juvenile pilocytic astrocytomas and diffuse astrocytomas ```

Answer 12

associated with increased ICP, seizures, visual disturbances, can be similar to medulloblastoma depending on their location

Answer 13

``` #curative intent for Cerebellar astrocytomas # malignant astrocytomas and glioblastoma, the goal is maximal resection ```

Answer 14

``` # avoid in kids <3-5 if possible #prolong time to tumor progression if there was an incomplete resection of malignant astrocytoma or glioblastoma ```

Answer 15

``` #multiagent, dose-intense #cyclophosphamide, cisplatin, carboplatin, etoposide, vincristine, carmustine (carboplatin is in most regimens since it is among the most active) #Chemo used where radiation deferred or failed or where surgery not a good option ```

Answer 16

Carboplatin 175mg/m2 IV weekly x 4 | Vincristine 1.5mg/m2 (0.05mg/kg if less than 12kg) IV weekly

Answer 17

``` #Worst prognosis: malignant astrocytoma and glioblastoma #Extent of resection important for cerebellar gliomas #The older the patient, the worse the prognosis ```

Answer 18

``` #Most frequently occur between 5-10 yo #Usually in pons, can be in medulla and midbrain ```

Answer 19

rarely cause increased ICP until late in course Extra ocular muscle paresis and diplopia, facial weakness, cranial nerve dysfunction, personality changes Spastic gait, hemiparesis

Answer 20

``` #diffuse infiltrative (usually in pons, poor prognosis, median OS <1yr) #focal (in medulla or midbrain) - good prognosis if can be removed surgically +/- radiation – survival 50-100% ```

Answer 21

remove as much as possible while preserving neurologic function

Answer 22

Mainstay of treatment for diffuse infiltrative, also for palliation and to control neurologic symptoms

Answer 23

Only 650 cases/year in US 36% occur before 1 year of age 90% occur before 5 years of age Median age at diagnosis is 22 months old

Answer 24

#Arise in the adrenal medulla or paraspinal sites of sympathetic nervous system tissue (anywhere along the sympathetic tract) #A “small blue round cell” tumor like Ewing’s sarcoma, non-Hodgkins lymphoma, primitive neuroectodermal tumors and rhabdomyosarcoma #65% are abdominal (adrenal or paraspinal) and 20% are thoracic #Mets to lymph nodes, bone marrow, bone, liver and skin #70% mets dz at dx

Answer 25

Based on age, stage, and tumor biology #40% of kids have low to intermediate risk dz which is cured by surgery or surgery plus chemo #60% of kids will have high risk dz and these kids rarely survive even with conventional therapy #Low risk-not treated unless life/organ impacting tumor #Intermediate risk: chemo +/- surgery, but no XRT #High risk: Chemo, surgery, HSCT, XRT, cis-retinoic acid

Answer 26

5 yr OS for infants is about 90% and about 55% for older children Age 95% 5 yr DFS for kids with Stage 4 is about 35%

Answer 27

hyperdiploidy normal n-myc copy number (THIS IS INTRINSIC TO DZ) low LDH low ferritin high VMA/HVA ratio neuron-specific enolase <100ng/ml DNA CONTENT: HYPERDIPLOID (POOR= DIPLOID) expression of HA-ras p21 or TRK gene

Answer 28

Urine catecholamines vanillylmandelic acid (VMA) and homovanillic acid (HVA) are elevated in at least 85% of patients. The higher the VMA:HVA ratio, the better the prognosis. Neuron specific enolase elevated in 95% pts with widespread disease. Ferritin is produced by neuroblastoma cells and is elevated in 50% of patients with Stage III and IV disease.

Answer 29

Stage 1-4, plus 4S (which doesn’t fit the scheme of higher number = worse prognosis) 4S is localized primary tumor with dissemination limited to skin, liver and/or bone marrow (limited to infants less than 1 year of age) Usually hyperdiploid without N-myc amplification. GOOD OUTCOME. Mostly stage 3 or 4

Answer 30

resection can cure localized disease

Answer 31

not useful for disseminated disease even though neuroblastoma is radiosensitive

Answer 32

Used in all but stage 1 and 4S disease Cyclophosphamide, ifosfamide, doxorubicin, cisplatin, carboplatin, vincristine and epipodophyllotoxins have been used.

Answer 33

Differentiating agents (retinoic acid): used after stem cell transplant mIBG to target radiotherapy for metastatic neuroblastoma anti-GD2 ganglioside = ch14.18 monoclonal antibody USE AFTER TRANSPLANTATION (TX CAUSES A LOT OF PAIN - STIMULATES NERVES - USE OPIOIDS) USE retinoic acid + anti-GD2 ganglioside AFTER STEM CELL TX to improve OS

Answer 34

Surgery cures > 90%. N-myc positive requires chemo

Answer 35

surgery Chemo if N-myc amplified or recurrence. Chemo includes cyclophosphamide and doxorubicin. Failures get cisplatin and etoposide. Can use XRT for residual disease after second look surgery cyclophosphamide 150mg/m2/day IV x 7 days doxorubicin 35mg/m2 IV on day 8 Repeat q3 wks x 5

Answer 36

50-70% cure rate with intensive therapy. Surgery, chemo, and possible radiation Ex: vincristine 1.5mg/m2 IV on day 1 cisplatin 80mg/m2 IV over 24 hours on day 1 etoposide 200mg/m2 IV over 4 hours on day 3 alternate with vincristine 1.5mg/m2 IV on day 1 cyclophosphamide 600mg/m2 IV on day 1 etoposide 200mg/m2 IV over 4 hours on day 1 carboplatin 500mg/m2 IV on day 1

Answer 37

Least responsive to chemo Survival depends strongly on age, infants respond to less aggressive courses than older kids Even with aggressive treatment, OS usually no better than 20% High risk = Stage 4, and stage 2,3,4S with N-myc amplification

Answer 38

Aggressive induction chemo Consolidation with intensive chemo OR high dose chemo, TBI, and HSCT SCT can be allo if there is a matched sibling, or auto

Answer 39

cyclophos 2.1gm/m2/day with mesna on days 1 and 2 (HUGE DOSE) doxorubicin 25mg/m2 on days 1,2, and 3 vincristine 0.67mg/m2/day as bolus or continuous infusion on days 1, 2, and 3 (max of 2mg over 72 hours) ALTERNATE with Cisplatin 50mg/m2/day on days 1 to 4 etoposide 200mg/m2/day on days 1 to 3 HOLD TX IF ANC <100K

Answer 40

Retinoic acid 160mg/m2/day x 14 days for 4 courses (helps neuroblastoma cells differentiate) Monoclonal antibodies to neuroblastoma antigens USE AFTER HSCT

Answer 41

Surgical resection will cure most Clinical course depends on age and liver involvement at diagnosis. If N-myc amplification, treat as high risk

Answer 42

``` #Due to loss of function in tumor suppressor genes ~500 cases/year in US ``` Peaks at 2-3 years of age, rare after 6 years sporadic and familial types Familial types tend to be bilateral and occur at younger age (1-2% of cases) Usually detected by caregiver who notices an abdominal mass 25% have hypertension

Answer 43

Favorable histopathology (85% of cases): well differentiated and resembles developing embryonic tissue Unfavorable histopathology: anaplastic, clear cell, rhabdoid Local spread – infiltrated renal capsule, involvement of renal sinus, tumor in intrarenal vessels Distant spread to: lungs, regional lymph nodes and liver Neuroblastoma displaces the kidney but Wilm’s distorts the kidney Use ultrasound to check for thrombus in renal veins and inferior vena cava. Stage is increased if thrombus attached to vessel walls

Answer 44

I = limited to kidney, complete excision, intact capsule, not ruptures, no residual II = extends beyond kidney, but completely excised. Lymph nodes negative III = Residual tumor present IV = hematogenous mets or lymph node mets outside abdomen V = bilateral disease

Answer 45

most important, ALL STAGES check both kidneys, can use chemo first to shrink tumor or if extensive vena cava involvement

Answer 46

if nodes involved or metastatic disease, peritoneal seeding, spillage during surgery or rupture (No abdominal exams) 2 DRUGS ARE RADIOSENSITIZERS - THESE DRUGS ARE HELD DURING CHEM

Answer 47

vincristine, dactinomycin, doxorubicin, and cyclophosphamide are the most active 1m2 kid = 30kg For kids less than 1yo, doses are cut in half after converted to mg/kg to reduce toxicity - KEY

Answer 48

#Dactinomycin 0.045mg/kg/dose (1.35mg/m2 for patients > 30kg (max 2.3mg) start within 5 days of nephrectomy during week 0 and then week 3,6,9,12,15,18 #Vincristine 1.5mg/m2 (0.05mg/kg for

Answer 49

#Dactinomycin 0.045mg/kg IV (max 2.3mg) within 5 days of nephrectomy during week 0, then on weeks 6, 12, 18, and 24 #Doxorubicin 45mg/m2 IV push (1.5mg/kg for

Answer 50

#Surgery and post op radiation to tumor bed #Doxorubicin 45mg/m2 on weeks 0, 6,12, 18, and 24 #Vincristine 1.5mg/m2 on weeks 1,2, 4-8, 10, and 11; then 2mg/m2 on weeks 12,13, 18, 24 #Etoposide 100mg/m2 daily x 5 on weeks 3,9,15,21 #Cyclophosphamide 440mg/m2 daily x 3 on weeks 6,12,18,24

Answer 51

#Based on stage and histology #Stage 1 is 96% 4 year OS #Stage 5 is 75% 4 year OS #Unfavorable histology: 55% for stage IV #Histology is the most important prognostic factor, with distant mets and lymph node involvement being important, also

Answer 52

#Can occur anywhere, usual sites are GU, extremity, head and neck, trunk, orbit and retroperitoneum, prostate #4 types: embryonal, alveolar, undifferentiated and botryoid #Embryonal: (resembles striated muscle) see in young kids with head and neck or GU #Alveolar: (resembles lung cells) seen more in older kids and involves trunk or extremities

Answer 53

Spreads locally and via lymph and blood. Primary sites of metastatis are regional lymph nodes, lungs, bone and bone marrow (lung is most common)

Answer 54

if tumor is resectable only 1/3 resectable all will relapse with surgery alone

Answer 55

for local control (have to hold dactinomycin for radiation) routine for higher stages =group 2-4

Answer 56

#most relapse without chemo - given by group #Group 1 (localized, complete resection) -vincristine and dactinomycin (VA) x 1 year with no XRT #Group 2 (microscopic residual disease +/- nodes) -Radiation with chemo – 90% local control VA x 1 year with radiation #Group 3 (localized, not resected)- Pulse vincristine/ dactinomycin/cyclophosphamide (VAC) for 1 year + radiation #Group 4 (metastatic)- Pulse VAC alternating with ifosfamide 1.8gm/m2 IV x 5 days plus etoposide 100mg/m2 IV x 5 days for 1 year plus radiation

Answer 57

vincristine 1.5mg/m2 IV weekly dactinomycin 1.5mg/m2 or 0.045mg/kg (2.5mg max) IV every 3 weeks. (Using mg/kg due to increased risk of VOD in younger kids) cyclophosphamide 1.2 or 2.2 gm/m2 IV every 3 weeks (using 1.2gm/m2 currently to try to decrease toxicity (sterility) without affecting survival rates)

Answer 58

Overall 70% long term survival Most important variable is clinical group or extent of disease at diagnosis, second most important is primary site. Histology is also of prognostic significance. Best to worst: Botryoid, embryonal, alveolar, undifferentiated Without complete tumor obliteration, cure is not possible. HSCT doesn’t improve survival in high risk patients

Answer 59

Hemorrhagic cystitis Infertility Cardiomyopathy Adhesions Secondary malignancy (ex. radiation-related sarcomas and secondary AML Renal Fanconi’s syndrome with ifosfamide

Answer 60

300 cases in US each year 75% of cases are unilateral (ONLY GERM MUTATIONS CAUSE BILATERAL) Majority in very young children 95% before 5 years and 66% before 2 years The RB gene is a tumor suppressor gene and it gets inactivated 2 Types: hereditary (40%) and sporadic (60%)

Answer 61

Leukokoria (lack of red reflex in eye) – white pupil Strabismus (having a squint) Red/painful eye

Answer 62

Kids with a positive family history have full eye exams shortly after birth and at 6 weeks of age and every 2-3 months until 2 years old. This is one of the very few pediatric tumors that can be screened.

Answer 63

Arises in retina Can extend locally or spread distantly Local spread = growth in intraocular space Mets occur when tumor grows along optic nerve, spread to CNS or spread via lymph or blood

Answer 64

Eye exam with ophthalmoscope Ultrasound CT Staging based on number and size of tumors and whether or not there is vitreous seeding

Answer 65

enucleation for advanced disease (not done as much as in the past). Can use laser photocoagulation or cryotherapy if the tumor is small enough

Answer 66

to try to control the disease and retain the eye and useful vision. increased risk of second cancers (OSTEOSARCOMA)

Answer 67

IV and or IT chemo if metastatic disease present. Can use it to minimize need for XRT or enucleation. Vincristine 1.5mg/m2 (0.05mg/kg if less than 36 mo) IV x 1 Etoposide 150mg/m2 (5mg/kg if less than 36mo) IV daily x 2 Carboplatin 560mg/m2 (18.6mg/kg if less than 36mo) x 1 Combination chemo and radiation is used for stage IV and V

Answer 68

90% survive retinoblastoma, but patients with germinal mutation tend to get second non-ocular malignancy (osteogenic sarcoma) Retention of vision depends on the size of the tumor and its location

Answer 69

Primarily seen in adolescents (during growth spurt) A high-grade sarcoma Usually occurs in distal femur, proximal tibia, or proximal humerus. Most common is distal femur Can involve flat bones (ex pelvis)

Answer 70

Bone diseases (osteogenesis imperfecta and Paget’s disease) predispose elderly to osteosarcoma Ionizing radiation Genetic predisposition (ex retinoblastoma and risk of secondary osteosarcoma) Alkylating agents

Answer 71

Pain/mass/swelling over the involved area About 20-25% present with metastatic disease. Most common site is the lungs

Answer 72

x-rays CT/MRI Biopsy Can see increased alkaline phosphatase and LDH

Answer 73

Stage 1 (low grade) Stage II (high grade) – most are high grade Stage III (distant mets) A OR B is if extramedullary (broken out of bone)

Answer 74

must remove the primary tumor for local control. Limb salvage or amputation Metastatic disease must be completely removed in order to get a cure need chemo also otherwise 80% recurrence

Answer 75

Osteosarcoma is not radiosensitive, so radiation is not used *this is a difference vs Ewing’s sarcoma*

Answer 76

relatively drug-resistant due to p-glycoprotein Few drugs are effective High dose methotrexate alternating with doxorubicin and cisplatin - NEED CLOSE MONITORING OF RENAL FUNCTION AND MTX LEVELS

Answer 77

Cisplatin 120mg/m2 IV over 4 hrs on day 1 Doxorubicin 25mg/m2/day on days 1, 2, and 3 as a continuous infusion Alternate with methotrexate 12gm/m2 IV over 4 hours on days 21 and 28 with leucovorin starting 24 hours from the start of methotrexate. (MAX methotrexate dose is 20 grams)

Answer 78

Give chemo for a few cycles, then assess tumor response at time of resection. Less than 90-95% tumor necrosis is associated with poor risk disease Shrinking the tumor with chemo prior to surgery improves the chances of limb salvage instead of amputation Overall, neoadjuvant chemo hasn’t improved outcome vs post-surgical chemo

Answer 79

Surgery and adjuvant chemo have 50-75% disease-free survival at 2-5 years. Overt metastatic disease has poor outcome Axial primaries (pelvis) have worse outcomes Age >20 is better, <10 is worse Females have better outcome Increased levels of alkaline phosphatase are associated with increased risk of metastatic disease and poor prognosis

Answer 80

Also most commonly seen in adolescents Considered a bone tumor, but can arise in soft tissue Primitive neuroectodermal cell tumor, small round blue cell tumor (unique translocation is t(11;22) Most frequent site is pelvis, then the femur, tibia, and humerus Can arise in any bone Osteosarcoma is usually in long bones in extremities, while Ewing’s is usually in the axial skeleton

Answer 81

Pain and swelling of the affected area May have systemic signs and symptoms (unlike osteosarcoma), especially with metastatic disease: fatigue, anorexia, weight loss and fevers Can be an extraosseous tumor (no bone involvement)

Answer 82

Without systemic treatment, over 90% of patients develop mets, mostly in the lungs. Can also spread to other bones and the bone marrow Highly malignant No universally accepted staging system Presence of metastatic disease is the important issue Elevated LDH is associated with metastatic disease and a poor prognosis Spread to lymph nodes is rare (as opposed to rhabdo, osteo and PNET which involve lymph nodes more commonly) Mets to paraspinal area are common

Answer 83

POSSIBILITY FOR COMPLETE RESECTION AND ANATOMY (QOL ISSUES, CHANCE FOR CURE) Role is for local control Can use surgery or radiation for local control Neoadjuvant chemo is given to assess tumor responsiveness and treat micrometastatic disease. Neoadjuvant chemo may improve resectability of tumor Can do limb sparing or amputation

Answer 84

very radiosensitive. Use for lesions that are difficult to remove surgically can be used if surgery would result in loss of nerve function

Answer 85

Vincristine 1.5mg/m2 IV Doxorubicin 75mg/m2 IV over 48 hours Cyclophosphamide 1200mg/m2 IV Alternating with: Etoposide 100mg/m2 IV daily x 5 days Ifosfamide 1.8gm/m2 IV daily x 5 days ONLY GIVE IE IN NON-METS DZ. DO NOT HOLD FOR MYELOSUPPRESSION

Answer 86

Patients with multifocal or metastatic disease at diagnosis have very poor prognosis High dose chemo and HSCT is now front line tx

Answer 87

``` #Most important factor is extent of disease at diagnosis #Increased LDH predicts metastatic disease and poor prognosis #Mets to bone marrow or bone has a poor prognosis #Multifocal disease at presentation has bad prognosis #Patients less than 10yo have better prognosis than older patients #Distal sites are more favorable #Unfavorable sites include pelvic or sacral lesions, intermediate sites include humerus, femur, and rib. #OS for distal extremity is 60-70% and pelvic is 35% #Tumor volume 100ml #Pathologic response to neoadjuvant chemo (good response is favorable prognostic sign) ```

Answer 88

no established screening tests anthracycline - delayed cardio tox more common cisplat - hydration 2x maintenance, correct CrCl for size ifos - renal Fanconi's = spill electolytes, mostly phos, and spill glucose (see at doses >70g/m2) infant dosing - reduce or by kg (with BSA nomogram can overdose kids) ~30kg = 1m2 BSA IT dosing - based on age (a dose in mg/m2 WOULD BE INCORRECT) slow use of new agents in clinical trials despite high clinical trial enrollment (~85%)

Answer 89

change ifos to cyclophos

Pediatrics Flashcards

(114 cards)