Oncology Flashcards

Question

Differentials of mediastinal masses - ant, middle, post

Answer 1

- Anterior: lymphoma, germ cell tumour - Middle: lymph nodes, TB, fungal, osteosarcoma, lymphoma/leukaemia (T cell) ; foregut duplication cysts - Posterior (neurogenic): neuroblastoma (\<10), neurofibroma, schwannoma - 80% of mediastinal masses are malignant 10% in ant superior mediastinum compress SVC/airway

Answer 2

Neuroblastoma Mets brain tumour Primary spinal tumour Ewings and Osteosarcoma Rhabdomyosarcoma Lymphoma / Leukaemia (Chloromas) - Local or radicular pain \>80% - Motor weakness, sensory loss, incontinence (caudal equina) - Paraplegia/quadriplegia can progress rapidly - Emergency MRI, surgery/radio/chemo +/- dexamethasone Better outcome if treatment started within 10 days onset symptoms

Answer 3

- L'Asparaginase/PEG asparaginase - Etoposide - Carboplatin - Amifostine - Platelet transfusions + newer moncolonal antibodies cause allergic reactions - Premedications given to reduce risk

Answer 4

Doxorubicin, dactinomyin, danorubicin, vinblastine, vincristine Rx Attack new syringe, aspirate as much as possible, involve plastics

Answer 5

Alpha haemolytic strep (strep mitis/strep pleuridans) Always treat these patients with tazocin + vancomycin

Answer 6

Methotrexate, doxorubicin Mx Hyperhydration Leucovorin (folinic acid) rescue with HD MTX Oral hygiene Antifungals if high risk GCSF Mouth wash, pain relief Gut rest and IVN for typhilits Immune suppression for GVHD

Answer 7

Doxorubicin (anthracyclines) + thoracic radiation - worse with puberty, pregnancy, high intensity exercise - Give dexrazoxane (iron chelator) prior to anthracycline in high risk patients

Answer 8

\>38 ̊C on 2 occasions or \>38.5 ̊C on one occasion AND ANC of \<0.5 x 109/L, or expected neutropenia from recent chemo • Urgent review because: – Chemotherapy causes decreased number and function of immune cells – Radiation complication – Surgeries – Breakdown of mucocutaneous barriers – Foreign bodies (CVL, grafts etc.) – They can decompensate very quickly Most common culprits are staph epi, streps, gram negative rods. But most rapidly lethal are gram negatives (E. Coli, Pseudomonas, Kliebsiella) – Microbiological diagnosis only made in 10-30% • Antibiotics should be started within the first hour – Tazocin (Piperacillin/Tazobactam) monotherapy – HD araC exposure/AML/BMT–add Vancomycin – Known ESBL–add Amikacin – If shocked–add Amikacin and Vancomycin – Avoid Amikacin if cisplatin exposure – If shocked, but cisplatin exposure or risk of renal damage–use Meropenem – If low risk–consider Ceftriaxone as outpatient

Answer 9

- Ondansetron (5HT3 receptor antagonist) - can prolong QT - Dexamethasone (half Aprep if using) - Aprepitant (NK1 Antagonist) CI with IFOS, risk encephalopathy, dose reduce with steroids (toxicity) SE EPSE, long QT, NMS - Scopaderm patch (Hysoscine) ; Anticholinergic, CI with epilepsy and ileus. Use with metoclopramide - Dopamine antagonists - Metoclopramide/ Domperidone ; Prokinetic, risk EPSE ; acts on CTZ at floor 4th ventricle - Cyclizine (antihistamine) acts on Vestibular centre - Loraz (benzo) - anticipatory nausea Refractory nausea Olanzapine (antipsychotic) Nozinan (Levomepromazine) - phenothiazine, broad spectrum antiemetic Delayed emesis (24hrs-7days post chemo) is most common with cisplatin but also seen with high dose cyclophosphamide, doxorubicin, carboplatin and Ifosfomide. It is more likely when these drugs are used in combination.

Answer 10

• Can involve the whole of the alimentary tract from mouth to anus • Chemo: – MTX related mucositis • Infection: – Candida / Herpes causing stomatitis / esophagitis • Neutropenia: – Typhlitis / neutropenic colitis • GVHD of tongue / gut

Answer 11

Solid tumours - Wilms - Neuroblastoma - Brain tumour ALL (steroid SE) Post BMT (SE Ciclosporin)

Answer 12

GH deficiency (most commonly affected by radiation - causes linear growth failure) Precocious puberty Thyroid problems Gonadal failure( Primary - high FSH/LH ; central - low/normal FSH/LH) - 50% males infertile - 30% women need oestrogen replacement, check AMH 12 months post Rx, Ovarian US for follicle count - Can use Zoladex (GNRH analogue) to suppress menstruation and limit gonadotrophin effects of treatment Bone disease - Osteoporosis, Rickets Obesity, Metabolic syndrome, insulin resistance Nearly 1/2 patients will have 1+ of above

Answer 13

2% above average RF Radiation (Sarcoma, BMT, Hodgkins) ETOP / alkylating agents (Cyclophos/IFOS) - risk AML and sarcomas Genetic (Fanconi, Li Fraumenia, Retinoblasoma(Rb1) Hodgkin (mantle irradiation): breast (30-40% risk by age 50) and thyroid cancer Early off therapy (2-3 years) secondary AML Late (\>5-10 years) post RT - 2-5% V. Late (\>10yrs post treament ) - \>10% eg risk breast ca post Hodgkins RT

Answer 14

Cisplatin (up to 70%), worse if had gentamicin, amikacin, frusemide treatment. 30% require hearing aids.

Answer 15

Mediastinal germ cell tumour Breast cancer

Answer 16

- Medulloblastoma - Neuroblastoma - Ewings - Wilms - Hepatoblastoma - Retinoblastoma

Answer 17

- Is a result of donor T lymphocytes directed against recipient tissue antigens. - Fever, rash, diarrhoea, LFT derangement and pancytopenia. - It has a very poor prognosis and is almost universally fatal - Prevent by using irradiated blood.

Answer 18

Good prognostic factors: Age \<1 Hyperdiploidy Whole chromosome gains Poor prognostic factors: Amplification of the N-myc proto-oncogene Segmental chromosome abnormalities

Answer 19

- Supependymal giant cell astrocytoma (5-15%) - benign, slow growing, wall lateral ventricles - Cerebral cortical tubers (90-100%), associated with seizures - Subependymal hamartomatous nodules - Everolimus is the standard of care for unresectable lesions

Answer 20

- Delayed neuro changes after tumour resection - Cerebellar mutism, irritability, difficulty verbalising, emotional lability, nystagmus - 20% incidence after resection medulloblastoma - Mutism resolves ~1m, other neuro symptoms persist

Answer 21

Ewing's, alveolar rhabdomyosarcoma, neuroblastoma

Answer 22

AD cancer predispostion syndrome caused by germline mutations in the tumour suppressor gene APC. Inc risk bowel cancer and hepatoblastoma

Answer 23

- ALL (inc 20x) ; T21 poor prognostic in ALL - Acute megakaryoblastic leukaemia (inc 500x) (AML \> ALL in first 3 years life) ; AML good prognostic in T21 - Transient myeloproliferative disease (peripheral blasts, usually in first 3months life, most resolve) - 20-30% of these develop AML within 3 years life (mean 18months) T21 ++sensitive chemo, need to dose reduce MTX

Answer 24

- Mutation in TP 53 gene, tumour suppressor gene - AD, FHx early-onset cancers - Soft tissue sarcoma, osteosarcoma, breast cancer, leukaemia, brain cancers, adrencortical

Answer 25

AR mutation BLM gene Associated Leukaemia, lymphoma, CNS tumors

Answer 26

Leukaemia, lymphoma, CNS Mutation ATM tumor suppressor gene, AR

Answer 27

- 85% sporadic, mutation in 11p15.5 causing over-reactivity of IGF2 gene - From abnormal methylation or uniparental disomy - 10-20% develop malignancy - hepatoblastoma, neuroblastoma, Wilm's, rhabdomyosarcoma, adrenocortical tumour Of the tumours in BWS, -43% are Wilms Tumour -20% hepatoblastoma and -7% adrenal cell carcinoma. - Abdo USS 3-monthly until age 8, AFP every 6 weeks until age 4 - After 10 years, the risk approaches the baseline risk of cancer in the general population.

Answer 28

Multiple basal cell ca ; medulloblastoma AD mutation PTCH gene

Answer 29

AD mutation VHL gene Haemangioblastoma cerebellum and retina Phaeochromocytoma Renal ca

Answer 30

Parathyroid Pancreatic islet Pituitary

Answer 31

Medullary ca thyroid Hyperparathyroidism Phaeochromocytoma AD mutation RET proto-oncogene

Answer 32

Late (\>18mo off treatment) Early (\>18mo since diagnosis, \<6mo off treatment), 50% survival Very early (\<18mo since diagnosis), poor prog 20-30% survival T cell ALL relapse has poor prognosis, \<30% survival

Answer 33

- Mutation of NF-1 on Ch17, unable to produce neurofibromin - AD, variable expression - Neurofibroma, schwannoma, optic glioma, astrocytoma, pheochromocytoma, malignant tumour from plexiform neurofibroma

Answer 34

- Familial retinoblastoma - germline RB1 mutation - Li-Fraumeni - mutation in tumour suppressor TP53 - Neurofibromatosis 1 - mutation of NF-1 gene on Ch 17 - Beckwith-Wiedemann - mutation in 11p15.5 - Trisomy 21

Answer 35

Gonadal (30%) or extra-gonadal (70%) - sacrococcygeal, retroperitoneal, mediastinum, neck, pineal region

Answer 36

- Gonadal 30%, extra-gonadal 70% - Range from undifferentiated embryonal carcinoma to mature teratoma (pure teratoma has no metastatic potential) - Gonadal: testicular swelling, pelvic pain, ovarian torsion, abnormal or precocious puberty - Inc risk with undescended testes - Ix: AFP and b-HCG - Can metastasise to lungs, liver lymph nodes - Tx depends on type/location. Chemo is cisplatin and carboplatin

Answer 37

- 90% of all renal tumours - Predisposed by nephrogenic rest (foetal tissue persisting into infancy) - Abdo mass (75%), haematuria, constipation, pain, HTN - Metastasises to lungs and IVC tumour thrombus - Low risk - surgery+observe. Other risk - surgery + chemo +/- radiotherapy - Overall survival \>90% for favourable disease

Answer 38

Embryonal tumour ; Small round blue cells Most common malignant renal tumour of childhood 6% of paediatric tumours From infancy to 5 years. Very unlikely past then. -Rarely dx \<6months -Best characterised gene is Wt1 deletion on 11p13 METS to LUNGS 95% unilateral 5% bilateral (at same time OR contralateral later in life) 90+ survival (unless anaplastic) Can be syndromic or non syndromic If known risk q3MONTHLY USS until age 8 If bilateral at same time -more aggressive chemo. Try to spare nephrons with surgery. If not remove --\> dialysis 1-2 years --\> transplant 20 years ESRF risk: 1% unilateral 12% bilateral Sx: Unilateral large mass (75% abdo mass only) Abdo pain Fever Painless gross haematuria HTN in 25% (increased renin from tumour) Complications: Bleed into tumour (with rapid enlargement) Anaemia Thrombus --\> 5-10% can extend into IVC Acquired vWF deficiency METS to lung, IVC thrombus via renal vein IX: XR, USS, CT, MRI USS is good to look at cystic vs solid, and differentiate from adrenal tumours DDX: Mesoblastic nephroma (\<3 months, solid tumour, mostly benign) Clear cell tumour (look for bone mets) Rhabdoid tumour kidney (look for brain mets; poor prognosis, rare; often haematuria presenting complaint) Prognostic factors: Age (\<2 =better), stage, tumour weight, loss of heterozygosity at 1p and 16q (poorer prognosis), anaplasia Rx: Surgery and chemo Low risk- actinomycin- D and vincristine High risk: Actinomycin D, Vinc, Doxorubicin Late effects: 2nd malignancy cardiac toxicity pulmonary disease renal failure

Answer 39

Most common soft tissue malignancy in children -Small round blue cells 3 types: 1. Embryonal (60%) - NO translocations, intermediate prognosis. Include botyroid variant(bunch grapes). Tumors resemble skeletal muscle 2. Alveolar 25-40% (translocations 1;13 or 2;13) and are most often in trunk and extremities and have poor prognosis. PAX-FOXO1 fusion associated poor prognosis 3. Pleomorphic (adult type, rare) -chemosensitive -3.5% of childhood cancers - Can occur anywhere but usually head and neck (including face, nasopharynx, midle ear, sinuses etc) -more likely alveolar in older children - Can disseminate early + LUNG METS -Alveolar METS everywhere incl BONE MARROW - Associated with neurofibromatosis and Li-Fraumeni syndrome Location Head and neck 25% ; Orbit 9% GU tract 24% ; Extremities 19% Sx: -Mass (may be painful) -Secondary sx from pressing on structures (anywhere from nose bleeds to cranial nerve palsies). Can often present with similar to common childhood conditions - If in extremities usually noticed after trauma and mistaken for haematoma -Can get vaginal rhabdo (grape like mass bulging through vaginal orifice) Ix: CT and MRI Staging - bone scan, chest CT, BMA, biopsy RX: 1.pre-operative chemo (VAC VI) 2. resection 3. post -op chemo (vinc, cyclophosphamide) 4. +/- irradiation depending on stage and site Survival: Embryonal - 40-90%, still curable if mets Alveolar 0-60% incurable if mets Risk factors: Older = bad Histology and staging (mets and site) Fusion protein (PAX FOXO1 poor prog) Late effects: -Impaired bone growth from radiation - second malignancy -Infertility from CYCLOPHOSPHAMIDE

Answer 40

Embryonal tumour - most common intra-ocular cancer in childhood - 4% malignancies (10% malignancy \<1 year age) - Most cases \<5 years old, median age 2; M=F 60% unilateral (10-15% germline RB1 mutation) 40% bilateral (germline RB1 mutation) - Hereditary and sporadic - Hereditary associated with younger age and bilateral retinoblastoma - Loss of function of RB1 gene on chromosome 13 - Small round blue cell tumour with rosette formation - Generally presents with leukocoria or strabismus - Advancing disease results in orbital inflammation, redness and pupillary distortion - pain if glaucoma present Can MET to CSF and spinal cord AT RISK of trilateral tumour (pineal ) tumour which can occur at the same time or any time after (presents with HEADACHES AND VI NERVE PALSY DDX: Other causes of leukocoria --\> ROP, coats disease, cataract, persistent hyperplastic primary vitreous IX: Dx made based on ophthalmological findings (under GA) as imaging is not diagnostic and pathology not required Orbital USS / Brain MRI Staging: MRI brain and spine, LP +/- BM trephine (can mets to BM) Rx: Focal chemo (etoposide, vincristine, carboplatin) If too large then enucleation of the eye If bilateral - focal chemo to reduce size + focal laser photocoagulation or cryotherapy +/-irradiation (significant deformity + increased risk of 2ndary tumour) If poor prognosis for vision or tumour in anterior segment - enucleation Prognosis - good \>95% Continue routine examination of eyes until age 7 If spread outside orbit, prognosis is poor Those with RB1(tumour suppression gene) mutation increased risk of secondary tumours, esp if exposed to radiation (Osteosarcoma, breast ca, soft tissue sarcoma) Late effects: Usually related to Rtx - cataracts -poor orbital growth deformities - lacrimal dysfunction - late retinal vascular injury Trilateral disease - bilateral retinoblastoma and pineal tumour (palsy of upward gaze - Parinaud) and hydrocephalus

Answer 41

Tumor originates in primordial neural crest tissue Most comon extra cranial solid tumour - 7% childhood malignancies ; 15% child cancer deaths - median age dx 22 months with 90% dx by 5 year old - Can occur at any site of sympathetic nervous tissue. about 50% adrenals, the rest along sympathetic ganglion - mets more likely if \>1 year old -mets lymph nodes, long bones, skull, bone marrow, liver and skin - lung and brain mets are RARE - Associated with neural crest disorders such as hirschsprungs, NF1 and central hypoventilation syndrome -Associated with Beckwith wiedemann syndrome or isolated hemihypertrophy - Family Hx in 1-2% (PHOX2B gene mutation and germline ALK mutations) 3 types of risk 1. High risk and malignant and aggressive (local/mets) -MYCM AMPLIFICATION -70% survival -HIGH dose chemo 13-18 months --\> causes aplastic anaemia so need autologous stem cell rescue + surgery + radiation +/- MIBG radioactive isotope, chimeric (immune therapy), retinoic acid 2. Intermediate risk local or metastatic \<18 month -95% survuval -2-8 cycles mod chemo +surgery -No transplant, no chimeric, rarely radiation 3. Low risk, localised and STAY that way -97-99% survival -small ones in babies usualy resolve spontaneously -larger ones cured with resection Sx: Can present with syndrome (see slide) Great mimicker so can be non-specific and hard to dx -metastatic disease can present with systemic sx, bony pain, cytopenia, proptosis, periorbital ecchymoses(raccoon eyes),. -localised disease can present as asymptomatic or mass-related sx such as spinal cord compression, bowel obstruction and SVC syndrome Dx: -Imaging - CT, MRI - Tumour markers such as catecholamine metabolites (HVA and VMA) in urine is elevated in 95% cases and helps to confirm dx -biopsy gold standard but dx can be made if small round blue cells in bone marrow and urine catecholamines are high - Staging - CT chest and abdomen, bone scan and at least 2x BMA and trephine for staging - MIBG scan (picks up cells with norepinephrine transport protein ; need iodine before and after scan as can be taken up by thyroid and cause damage) Neurobolastoma risk: -met vs local - easy to resect vs not -age (older = worse. cut off age 18 months) -histology - genetics = MYCN amplification and 11q missing are bad Rx depends on stage Surgery Chemo Chimeric (Dinutuximab) - Anti GD2 via ADCC (antibody dependent cell cytotoxicity), glycoprotein expressed on neuroblastoma ; also seen on normal pain fibres ; SE: ++pain, HR need 6 cycles multi agent induction chemo, then tandem autologous transplant and RT and post consolidation immunotherapy

Answer 42

HORNER SYNDROME - neuroblastoma originating in superior cervical ganglion -Unilateral ptosis, myosis, ahydrosis - Sx DO NOT resolve with tumour resection OPSOCLONUS-MYOCLONUS-ATAXIA syndrome -paraneoplastic syndrome of autoimmune origin - myoclonic jerking and random eye movement +/-ataxia - usually associated with lower risk tumour - may not resolve with tumour removal - can be progressive SWEATING and HTN - catecholamine release from tumour NEUROCRISTOPATHY SYNDROME -when neuroblastoma associated with other neural crest syndrome such as hirschsprungs, and congenital hypoventilation syndrome - Germline mutation of PHOX2B KERNER-MORRISON SYNDROME -tumour secreation of vasointestinal peptides causing intractable secretory diarrhoea -tumours generally biologically favourable PEPPER SYNDROME - massive involvement of the liver with mets disease +/- respiratory involvement HUTCHINSON SYNDROME - irritability and limp in young child associated with bony and bone marrow mets.

Answer 43

targets "GD2" which is present on healthy and unhealthy nerve cells -antibody dependent cellular cytotoxicity (ADCC) -attacks healthy nerves = ++pain. need morphine and ketamine -causes physiological instability, fever, oedema

Answer 44

Most common liver malignancy of childhood \<1% malignancies of childhood (liver tumours account for 1%, hepatoblastomas about 65% of this) -usually in children \<3 years -Alterations in APc/beta-catenin pathway -Environment predisposition LBW \<1000g (38 x relative risk) --\> not high enough to screen for -15% have genetic predisposition --\> BWS --\> FAP --\> Li-fraumeni, T18, NF-1, ataxia telangectasia, fanconi anaemia, TS Ix: AFP raised (non-specific as high in HCC and GCTs) --\> but used for monitoring response Can also have raised BHCG Biopsy gold standard RX: 1. resection key to cure (as much as 85% is fine with regeneration in 3-4 months!) 2. chemo in most Cisplatin/carboplatin (also treats mets) + sodium thiosulpahte (protects against SNHL) vinc and doxorubicin 3. Transplant if unable to resect +/- post-transplant chemotherapy The ONLY CONTRAINDICATION to TRANSPLANT: persistence of viable extrahepatic disease after chemo Prognosis: -\>90% with low staged with surgery and post chemo - 60% if unresectable tumour - 25% if pulmonary mets

Answer 45

-tumour that begins in cells that give rise to eggs or sperm -can occur almost anywhere in the body and can be malignant or benign -1/3 arise in gonads -2/3 are extragonadal as arise from aberrant migration and occur in the MIDLINE - appearance may mimic any cell in embryo (yolk) or extra embryonic (chorion) -types include teratoma (mature and immature) --\> benign Germinoma embryonal carcinoma Yolk sack tumor (raised AFP) choriocarcinoma (raised BHCG) Primary sites: -Gonadal - testes 25% (adolescents), ovaries 10% (adolescents -CNS--\> pineal (2/3), suprasellar (1/3), rare and aggressive ; Germinoma 60% CNS, Good outcome with RT -cervical --\> rare, teratomas/infants - MEDIASTINAL --\> 5% (adolescents) associated with KLINFELTERS - Retroperitoneal 10% infants/children - SACROCCOYGEAL 50% infants/children Sx: present as mass lesions If in CNS presents often as diabetes insipidus in adolescents. Or as precocious puberty or panhypopit RX: 1. Surgery 2. Cisplatin/carboplatin if cannot be resected +/-radiation (intracranial chemo +radiation as cannot resect

Answer 46

GORLIN SYNDROME -AKA basal-cell nevus syndrome -3% will get MB -PTCH pathway mutation TURCOT's SYNDROME -mismatch repair cancer syndrome (Lycnh, HNPCC) -Increased risk of CNS tumours and cororectal polyposis/cancer -high grade gliomas and MB in childhood/adolescence LI-FRAUMENI SYNDROME -TP53 -bimodal peak \<10 years abd 20-40 years - ASTROCYTOMAS \>\> MB

Answer 47

4 types -different histology and age onset 1. WNT activated -monosomy 6, classic histology -10% patients ; good prognosis -90% long term survival ; more common girls 2. SHH activated -PTCH pathway -lateral tumours - nodular desmoplastic - INFANTS have excellent prognosis -TP53 mutated tumour very poor prognosis 3. Non-WNT/non SHH -Group 3 --\> MYC amplification, large cell ANAPLASTIC, poor outcome -Group 4 --\> MYCN amplification, cassic or large cell anaplastic, intermediate outcome These guys are stratified into SJMB12 treatment and guides chemo + RTX

Answer 48

most common CNS tumour approx 20% - primitive neuroectodermal tumour ; - small blue round cell tumour (SBRCT), large cell(poorer prognosis( - peak age 3-9 years, M\>F (65%males) - post fossa (cerebellum, usually arises from vermis) - Predilection for CNS dissemination - up to 1/3 metastatic disease at presentation (CSF, nodule seeding in brain or spine) On MRI: - T1 scan enhancement -Cystic spaces seen on T2 Prognosis based on: - ability to resect (do better if \<1.5cm2 residual tumour) - stage ( AR if localised only aka M0, HR if M1-M4 or Anaplastic or if residual tumour) - histology ( if extensive nodularity and young child can rx with chemo only and no have to use Rtx) - molecular markers - Age \> 3 years (\<3 years do worse can cannot irradiate brain and spine) Ix: -repeat MRI of spine and CSF at least 10/7 after resection Rx: 1. maximal tumour resection 2. Rtx --\> reduced dose and tumour bed boost if AR; high dose RTX if HR 3. adjuvant during and after Rtx --\> St Jude's - Cisplatin, vincristine, cyclophosphamide - HD chemo is HR with autologous stem cell rescue (don't need for AR) Prognosis 5 years: AR --\> 75-80% HR --\> M1 about 60% --\> M2/M3 about 40% --\> SJMB-96 M1-M3 66%

Answer 49

Atypical Teratoid/Rhabdoid tumour - Deletion or mutation in INI1 gene (aka SMARCB1 gene) in tumour -Highly malignant -Usually occurs \<2 years of age - about 15% children \<3 years old with CNS -short hx, aggressive -occurs anywhere in brain and spine MRI: - Cystic and calcifications (subtle) Genetics: - can be germline mutation --\> if so at risk fro renal and soft tissue tumours - GTR of tumour assoc with longer median survival (12.5 months vs 9.25 months) -chemo curative in small minority -early Rtx used in majority of survivors if \>3 years old -unclear if Craniospinal irradiation necessar

Answer 50

- originates from cells lining lateral ventricle or central canal of the spinal cord -composed of neoplastic ependymal cells - third most common CNS tumour (10%) - 90% intracranial with 70% in the post fossa Poor prognosis if: - \<3 years old - Anaplastic - Disseminated disease - Infratentorial worse prog than supratentorial Not usually chemosensitive Surgery and RT mainstay of treatment

Answer 51

AKA low grade gliomas -low grade tumours (WHO grade 1 and 2) - comprise the largest group of CNS tumours in children -most common is juvenile pilocytic astrocytoma --\> 2/3 occur in POST FOSSA involving the cerebellum - Associated with NF1 (optic pathway gliomas) --\> also respond better to chemo - Large and cystic - Cause pressure effects and visual impairment (if involving the optic pathway -indolent --\> can be stable or regress - 3 places --\> posterior fossa (cerebellum), supratentorial and (optic pathway), - Almost all tumours involving the OPTIC pathway are JUVENILE PILOCYTIC ASTROCYTOMA Only 5% LG glioma present in optic pathway but \>70% OPG due to NF1 Histo: low to mod cellularity with ROSENTHAL FIBRES Genetics: single pathway - (B) RAF pathway aberration --\> MEK inhibitors disrupted Rx: - usually just observe with interval examinations and periodic CNS imaging - surgery +/- chemo (if non-resectable) +/\_ RTX if symptomatic exp if visual disturbances - chemo --\> carboplatin, vinc, vinblastine - Targeted therapy with MEK inhibitors for single pathway disease Prognosis 85-90%

Answer 52

Locally infiltrative astrocytomas 2 kinds: 1. Anaplastic astrocytoma (grade III) 2. Glioblastoma multiforme (grade IV) BUT \<10% leptomeningeal spread at time of dx Genetics poorly understood: P53, high Ki67 (mitotic index) Rx: 1. surgery --\> unlikely to get GTR 2. Rtx + alkylating agents (TEMOZOLAMIDE) Prognosis: \< 2 years progression free \<20% Prognostic factors: - degree of resection - grade - P53 expression (+ve =good prognostic factor) - proliferation index (high Ki67 = bad) - younger \<3 years better prognosis

Answer 53

A common type of brainstem glioma - usually dx 5-10 years old - Grade II-IV BUT prognosis based on mutation landmark = Histone H3.3 NOT grade H3.3 gene mutations do worse - 80% have H3.3 gene mutation (histone = protein replication and formation) Sx: Classic triad - Cerebellar signs (ataxia, dysmetria, dysarthria) - Long tract signs (increased tone, hyper reflexia, clonus, +ve babinski, motor deficit) - isolated or multiple nerve palsies (uni or bilateral) Ix: MRI diagnosis (+clinical signs) - T2 hyperintense -T1 hypotense (usually) - \>50% in PONS - Diffuse changes -BASILAR artery encasement in \>50% -Biopsy NO effect of survival so only if clinical trial available and trained surgeons Prognosis: At 2 years, approx 20% with \<10% chance of no disease progression

Answer 54

NEUROCOGNITIVE: -serial decrease in IQ \<7 years --\> as in declines relative to peers as not progressing in learning --\> if at least 7 years old when IQ projection is -0.42 pts/year --\> If less than 7 years old IQ projection is -4.82 pts/year (note in normal ppl IQ plateau's about 16-20 years) - spatial learning difficulties -adaptive behaviour deficits -academic failure - Deficits worsen with time Psychological Endocrine/fertility- GH deficiency is most common followed by TSH and ACTH (and many others) Neurological Secondary cancers Ototoxicity Vision (life long damage)

Answer 55

- Cyclophosphamide (alkalising agent) - Etoposide (topoisomerase II inhibitor) - Doxorubicin and danorubicin (anthracyclines, topoisomerase II inhibitors)

Answer 56

- Parents are haploidentical matches to patient (i.e. patient shares 50% with Dad, 50% with Mum) - 1/4 chance of having a complete HLA matched sibling

Answer 57

• Recurrent headaches am, nausea or vomiting without deficits, lethargy suggest ↑ICP • Sun setting eyes (superior colliculus control vertical eye movments) • Sudden onset of cranial nerve palsies III,VI,VII • Papilloedema • Irritability • Listlessness • Failure to thrive • Progressive macrocephaly • Older children more likely than infants to have localising neurological signs • Change in personality • Change in gait • “Learning Disabilities” in older children • Cranial nerve palsies • Deterioration of vision • Strabismus • Other Symptoms – Genetic predisposition syndromes – Family history

Answer 58

Neuro‐Imaging – MRI Brain and spine (MRA/diffusion/Spectroscopy/fMRI/DTI) – low threshold for GA or sedation – anatomical details are key • Procedures – Surgical resection or biopsy (safe maximum resection) – LP for CSF cytology (10-14 days after procedure) • Laboratory Studies – May include α‐FP and β‐HCG – blood and CSF (marker GCT) – Pituitary hormones

Answer 59

Atypical Teratoid / Rhabdoid tumours (ATRT) • Biallelic inactivation of SMARCB1 in majority (previously INI1, SNF5, BAF47), INI loss in tumour. • Check germline mutation – at risk for renal and soft tissue tumours ; screen siblings/parents

Answer 60

G0 resting phase G1 preproliferative phase - L asparaginase S phase (DNA replication) - cytarabine - antimetabolites - MTX, 6MP, G2 phase - Etoposide (topoisomerase inhibitor) - Bleomycin M phase (mitosis) - Vincristine, vinblastine (vinca alkaloids) Non phase dependent drugs Anthracyclines Alkylating agents

Answer 61

a delayed effect that results from the interaction of certain chemotherapeutic agents (doxorubicin, daunorubicin, or actinomycin-D) with radiation. After radiation therapy, an erythematous rash in the previous radiation field develops. The rash is geographic, usually precisely following the outline of the radiation field. Many of these occur months after the radiation treatment

Answer 62

5 Ts Teratoma (GCT), Thymoma, Thryoid mass T cell leukaemia Terrible lymphoma

Answer 63

Interfere with DNA synthesis Cyclophosphamide, Ifosfamide, melphalan DNA alkylation causes cytotoxic effect Dose Limiting effect is myelosuppression SE cyclophosphamide - Haemorrhagic cystitis (prevent with Mesna) - Myelosuppression - N&V - Infertility - Alopecia - Neurotoxicity Ifos - renal issues - fanconi syndrome - haemophilia cysts (use mesna to prevent) Can get secondary malignancies Mesna acts as a detoxifying agent. It is given as an adjuvant therapy and binds to acrolein in the urine, which creates an inert thioether that is excreted.

Answer 64

Cisplatin is platinum analogue Ototoxicity (irreversible High freq hearing loss) Nephrotoxicity (renal fanconi) Delayed nausea reversible sensory neuropathy

Answer 65

Doxorubicin, daunorubimcin Metabolised by liver, 75% biliary excretion Liver dysfunction needs dose reduction Use in ALL and solid tumours Cardiotoxicity - related cumulative dose, increased risk female Radiation recall Mucosisits, Myelosupp, N&V, alopecia Secondary malignancy (AML)

Answer 66

G2 phase inhibition of topoisomerase 2 Use solid tumors, AML, HL SE Myelosuppression N&V, mucositis, alopecia 2nd malignancy (AML)

Answer 67

inhibits dihydrofolate reductase (folic acid antagonist) Cell death from DNA interference (S phase) SE: Mucositis, myelosupp, renal toxicity, hepatitis, neuro SE (GBS like syndrome), pnuemonitis Intrathecal (CNS necrotising leukoencephalopathy) Can use folinic acid (Leucovorin) to reverse SE Interacts with cotrimoxazole

Answer 68

Pyrimidine analogue, Inhibits DNA polymerase (S phase) 90% excreted by kidney Myelosupp, mucositis, N+V Conjunctivitis (steroid eye drops) CNS - acute cerebellar syndrome

Answer 69

Vincristine, vinblastine Binds to tubulin in M phase - inhibits mitosis (antimicrotubule agent) Peripheral neuropathy (Vinc\>vinb) Jaw pain Extravasation - vesicant Constipation, alopecia SIADH Minimal myelosupp Vincristine is fatal if given IT

Answer 70

Used in ALL, inhibits protein synthesis (G1) Anaphylaxis Hyperglycaemia Pancreatitis Coagulopathy / platelet dysfunction Encephalopathy

Answer 71

inhibits purine synthesis (S phase) SE Myelosuppression (worsened by allopurinol ; increased 6TGN) Mucositis

Answer 72

* HLA mismatch (also causes GVHD) * Low TNC dose from donor graft * Previous multiple transfusions (older child \>10) * Infections * GVHD * Drugs(myelosupp - aciclovir, cotrimox, MTX)

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