Oncology - Lecture Materials

Oncology General numbers 1/600 risk m>f (just) Most common cause of death in 5-14yrs 2nd most common cause of death in 15-19y Mechanisms of inherited Cancers Mutation / deletion of tumour suppressor genes – needs loss of both copies Activation of oncogene Translocation à overexpression of growth factors Management principles Chemotherapy Systemic à decreases risk of tumour recurrence Adjuvant = post surgery Neoadjuvant = pre surgery Cell cycle G1 = gap – synthesis of components needed for DNA synthesis S = synthesis of new DNA G2 = gap – preparation for mitosis M = mitosis (cell division) Differentiation Chemo = makes cells develop down a given cell line and the apoptose. Used as adjuvant to chemo e.g. ATRA Aggressive tumours have high mitotic index = respond well to chemo because chemo works by damaging DNA/blocking DNA synthesis/interfering with processing of DNA / interrupting mitosis Chemo doesn’t kill all cells because normal cells have low turnover Agents may be phase specific or cycle specific (act all the time) Side effects Short term - Vomiting, myelosupression, alopecia, mucositis, hepatitis, haemorrhagic cystitis, nephrotoxicity, encephalopathy Long term – cardiotoxicity, pulmonary fibrosis, nephrotoxic, infertility, hearing loss, secondary malignancy High dose therapy + stem cell transplant “Conditioning” = myelo-ablative dose of chemo + total body irradiation à stem cell transplant Radiotherapy Dose and fractionation (no of doses) vary Used in Hodgkin’s, neuroblastoma, Wilms, soft tissue, Ewing’s, and most CNS tumours Plan by CT/MRI Immobilise and target using masks & tattoos Protect surroundings with lead shields Can use some chemo elements to increase effectiveness = “radiation recall” is used afterwards Side effects Acute – N&V, cutaneous erythema/desquamation, diarrhoea, myelosupression, pneumonitis, hepatitis Later SE – cardiotoxic, lung & renal dysfunction, MSK hypoplasia/asymmetry, low T4, decreased spinal growth, hypopituitarism, neuro-psych, cataracts, infertility, new primary tumours (approx 5%) Surgery Biopsy Resection (primary or post chemo) Side effects of chemo & radiotherapy Most chemotherapy drugs act by interfering with replication & division of DNA during cell division Early Marrow suppression à low plts & WCC à haemorrhage & infections Febrile neutropenia Give broad spectrum cover (aminoglycoside + Beta lactam). If indwelling line add in cover for coag negative staph. If persistent fever add antifungal cover as well G-CSF has been shown to decrease the duration of neutropenia, fever & frequency of infection Most commonly find Coag Negative Staph on B.Cult Tumour lysis syndrome – raised urate, K+, PO4, low Na, precipitates in kidneys à obstruction. Highest risk is when raised WCC & bulky solid tumour. Give hyperhydration & xanthine oxidase inhibitors Gastro - N&V (antiemetic), Poor nutrition due to malabsorption Neurotoxicity – vincristine à peripheral neuropathy, SiADH, low Na+ & seizures Others – Allopecia,. Hepatotoxicity, Steroid problems Specific to drugs: Doxorubicin à cardiotoxicity Cisplatin à renal failure & deafness Cyclophosphamide à haemorrhagic cystitis Vincristine à Neuropathy & disruption of microtubules à loss of deep tendon reflexes Cytosine Arabinoside à conjunctivitis & cerebellar toxicity Bleomycin à lung damage Asparaginase à pancreatitis Isosfamide à renal tubule damage Late Short stature – pituitary radiation à decreased GH Endocrine – damage to glands Infertility – due to gonad irradiation / damage from alkalating agents e.g. cyclophosphamide Cateracts – due to lens irradiation Cardiotoxicty - doxorubicin Cognitive dysfunction due to neurosurgery / radiotherapy (esp if < 5 yrs) Avascular necrosis Secondary tumours – due to radiation Social & educational delay Presentations of malignancy Pancytopenia – pallor, infections, bruising. Due to marrow displacement e.g. leukaemia /disseminated malignancy LN/Unexplained masses >2cm diameter with progressive enlargement Non tender, rubbery, hard, fixed Supraclavicular/axillary Assoc with pallor, lethargy etc +/- hepatosplenomegaly Respiratory symptoms – new/changing wheeze = intrathoracic mass Bone/Joint pain/swelling – persistent back pain is rarely innocent. E.g. leukaemia, mets, primary spinal tumour Abdo mass Progressive enlargement + malaise e.g. neuroblastoma Or incidental e.g. Wilms Raised ICP – early morning headaches, vomiting, ataxia, papilloedema, CN III & VI palsy Neuro signs – CV palsies, cerebellar signs (inc head tilt), visual disturbance, abnormal eye movements, gait change, motor/sensory/behaviour disturbance, decreased school performance, loss of milestones, increased HC Endocrine – poor feeds / FTT (diencephalic syndrome), DI, GH def, Precocious puberty Oncology Emergencies Tumour Lysis Syndrome Rapid lysis on starting chemo à release of cell contents Causes high K, Urea & PO4, with low Ca & metabolic acidosis Exceeds renal capacity to handle altered electrolytes Causing ARF Seen in ALL/NHL and others Can occur spontaneously/after single dose of steroids Rx Hyper-hydration before & during chemo Ensure good renal output Urate precipitation – use allopurinol Increase fluids and haemofiltrate if required Salbutamol/resonium/dextrose/insulin for hyperkalaemia Hyperviscosity Syndrome Assoc with high WCC in leukaemia Sludging of blood in cerebral veins Rx – hydration, urate oxidase, chemo, Transfuse only if essential (and do it slowly), leucophoresis may aid symptoms SVC obstruction Due to mediastinal masses Can also à airway obstruction Dyspnoea, chest discomfort, hoarse cough, plethora of vessels on CXR, engorged chest wall veins, venous dilatation of optic fundi Acute abdomen Most commonly neutropenic enterocolitis/thyphilitis Bacterial invasion of wall à inflammation / infarction / perforation / sepsis & coagulopathy High mortality Can be masked by steroid used Raised ICP High dose dex to reduce cerebral oedema Cord compression Back pain, gait change, decreased sensation to legs, bladder & bowel Can be due to neuroblastoma, sarcoma, lymphoma, or CNS tumour Supportive Care Infection – fever = emergency Febrile neutropenia Fever > 38 + neuts < 1.0 Viral infections If zoster contact à acyclovir + IVIg HSV can cause painful leg ulcers Fungal PCP Inc aspergillosis, hepatic candidiasis and abscesses Pneumocystis Carinii Jirovecii Raised RR, dry cough and O2 requirement Haematology Bld + plt Tx as required Blood products should be leucodepleated to reduce viral transmission & reactions Irradiated blood needed for BMT & Hodgkin’s Renal Close attention to electrolytes as chemo/abx/anti-fungals can à dysfunction N&V Esp due to cisplatin/ifosfamide 1st line = domperidone/metoclopromide 2nd line = ondansetron (5-HT antagonist) + dexamethasone Cyclizine is good for CNS tumours Nabilone / chlorpromazine in severe cases Nutrition & mucositis Poor nutrition due to malig, chemo & infection Mucositis – due to chemo/radio therapy à pain + diarrhoea Rx – analgesia, good oral hygiene & antiseptic mouth washes Constipation – laxatives, less constipating opiates Bowel obstruction – antispasmodics, stool softeners, octreotide (reduces secretions & vomiting) Convulsions – diazepam/midazolam Cord Compression – Dex, radiotherapy, bladder & bowel management Dyspnoea – position, fans, opiates, benzos, O2, steroids Increased secretions – hyoscine, glycopyronium Anxiety/depression – diazepam, levomepromazine, amitriptyline Pruritus – cimetidine, antihistamine Haematological – Tx only for Sx improvement/quality of live. Topical tranexamic acid/adrenalin is useful Palliative care May still involve chemo/radiotherapy/surgery Symptom control Pain = usual ladder à Subcut at terminal stage Leukaemia = 1/3 of all childhood cancers 80% ALL 20% AML Downs have 30x ppn risk ALL Malignant clonal proliferation of white cell precursors Can form leukaemic deposits in spleen, LN’s, eyes & meninges Incidence 1/25000 = commonest childhood malignancy Peak 2-5 yrs (2yrs in girls, 3yrs in boys). Slightly more common in girls Risk factors Ataxia telangectasia, Downs (20-30x ppn risk), Fanconi anaemia, Hodgkin’s, Klinefelters & radiation exposure S&S: Short Hx of pancytopenia, pain (marrow expansion) and LN 15% = Insidious onset General - Anorexia, lethargy, cold that is slow to clear Marrow infiltration à bone & joint pain, anaemia, low WCC, petechiae Reticular endothelial infiltration – LN & Hepatosplenomegally à SVC obstruction Organ infiltration CNS à headaches & vomiting with raised ICP & nerve palsies, papilloedema. Testis à testicular enlargement Congenital Leukaemia can à blueberry muffin spots Ix – exam (inc. testes), marrow, CSF, CXR ↓RBC, WBC & platelets CSF to assess CNS involvement (1-2% with CNS signs) Blood film to assess cell lineage (+ marrow, biochem, virus serology) Prognosis = approx. 80% survival. Poor prognosis if WCC > 100 at presentation Age > 10 yrs < 1 yr = very poor. Cranial / testicular involvement Relapse on treatment Poor if chromosome translocation 9:21 = Philadelphia chromosome, MLL gene t(4:11) or AML1 amplification Also poor if poor response to initial induction chemo G better survival than B 70% long term survival Rx Induction – 4/52 as inpatient aiming for < 5% blasts NB: rapid lysis of cells, à ↑ K+, ↓Ca2+, urate neuropathy, renal failure) = “tumour lysis syndrome” à give allopurinol Consolidation – CNS prophylaxis (weekly Intrathecal methotrexate) Maintenance – 2-3yrs (2y for g, 3y for b) of… Oral chemo (methotrexate + mercaptopurine) to aim for mild marrow suppression WITHOUT low Neuts AND monthly IV vincristine with 5d oral dexamethasone + 3/12ly Intrathecal methotrexate Transfuse as needed. PCP prophylaxis (cotrimoxazole) Relapses – can be bone, marrow or extramedullary (CNS/testes) à re-induction & consolidation + further 2yrs of maintenance BMT for highest risk patients Acute Myeloblastic Leukaemia (AML) – blast cells resemble myeloid precursors Classified by FAB system into M1-7 15-20%, evenly distributed throughout ages, 10% twin-twin risk S&S: clinical presentation similar to ALL, fewer LNs CNS involvement rare Can have gum hypertrophy / proptosis / skin nodules due to leukaemic infiltrates May present with chloromas (solid masses of myeloblasts around orbits, spinal cord or skull) Ix – 80% will have chromosomal problems in the marrow Myeloblasts have prominent cytoplasm with granules and Auer Rods, convoluted nuclei many of which stain with myeloperoxidase and Sudan Black Rx: 4-5 courses of intensive myelosupression with NO prolonged maintenance Marrow transplant if poor prognosis Prognosis - 80-90% achieve remission, Favourable outcome if t(15:17), t(8:21) or inv(16) Poor prognosis if monosomy 7 High risk if slow to respond / transplant during 1st remission Worse outcomes if chromosomal abnormalities Chronic Leukaemias (rare) Excessive ppn of mature white cells Adult Chronic Myeloid Leukaemia Anaemia, splenomegaly, high WCC, responds to chemo Juvenile Chronic Myeloid Leukaemia Skin rashes, lymphadenopathy, fever, bleeding, high HbF, death from infection or progressive marrow failure. Only Rx = marrow transplant Lymphoma Arise in LN à firm, non tender nodes Mediastinal LN à cough / collapse due to compression Hodgkin Lymphomas Twice as common as NHL 2 peak incidences (20s & 50+). RARE at < 5yrs Linked to EBV Lymph tissue hyperplasia with reed-sternberg cells (owls-eye nucleus) Reactive inflammatory infiltrate & granulomata, cellular immune deficiency Subtypes Classified into classical / lymphocyte predominant (localised with better prognosis) • Nodular sclerosing 50% • Mixed cellular 40% • Lymphocyte predominant 10% • Lymphocytic depleted = RARE S&S: Slow growing Progressive painless LN in >80% of cases 70% cervical, 20% axillary, 10% inguinal Weight loss (min 10% in 6 months) Systemic upset, night sweats (poor prognosis), persistent fever, pruritus, hepatosplenomegaly, Dissemination occurs late Rare presentations: Biliary obstruction Bone marrow involvement (pancytopenia) Spinal cord compression, and Immune diseases such as autoimmune haemolytic anaemia, thrombocytopenia or nephrotic syndrome. Staging = Ann Arbour Staging 1. Single LN region / single organ 2. 2+ regions on same side as diaphragm OR 1 organ + 1 region 3. Disease on both sides of diaphragm 4. Diffuse disseminated disease Prognosis 90% 5yr survival (97% in stage 1, 70% in stage IV) Poor if Fever, night sweats, wt loss or mass > 10cm Mixed cellularity on Bx Lymphocyte depleted Presentation with PUO >60yrs Reed-sternberg cells on marrow (indicates spread to marrow) Rx: multi-agent chemotherapy / radiotherapy if local à 90% long term cure Can à sterility for boys, but not girls Non-Hodgkin Lymphoma Peak 9yrs Majority are highly malignant proliferation of lymph tissue (can double size in days) T-cell = 40-50% (mediastinal mass) B cell = 30-35% (abdo mass) Remainder lymphoblastic S&S: fever, malaise, enlarged LN, multifocal signs, airway / SVC obstruction (due to enlarged LN), can be multi-focal including CNS Presentation by site (LN, pain, obstruction, ascites, resp sx, SVC obstruction, pancytopenia) Divided into Lymphoblastic (30%) – 90% T cell, 10% pre-B cell. Anterior mediastinal mass Mature B cell (50%) = Burkitts / atypical Burkitts. Abdo/head/neck/marrow/CNS Anaplastic large cell lymphoma - <20% Rx: multi-agent chemo, marrow transplant à approx 75% survival Lymphoblastic = treat as ALL Others = short dose intensive à HIGH tumour lysis risk Prognosis >70% overall >90% if localised Relapses tend to occur early & if they do = limited salvage options with poor survival Burkitts Lymphoma Small, non-cleaved cell (SNCC) type of NHL Assoc with EBV (EBV also causes increased risk of lympho-epithelioma and Hodgkin’s disease 90-95% of Burkitts Lymphoma in Africa are assoc with EBV (only 20-30% in USA) Chronic stimulation of B lymphocytes by B lymphocytes by EBV à chromosomal transformation à malignancy Increased risk in Africa as chronic malarial infection à decreased immune surveillance by genetically altered cells à increased BL Most commonly found in Jaw & is most common childhood Ca in east Africa & New Guinea Mean onset age = 5 years Good prognosis once treated CNS tumours Most common solid tumour (25% of total) Usually present late 2/3 infratentorial - raised ICP, headaches, vomiting, cerebellar ataxia 1/3 supratentorial - raised ICP & focal signs, hypothalamic-pituitary dysfunction or visual impairment 1o spinal tumours are rare à cord compression CNS mets of extra-cranial tumours are rare in children Raised ICP needs prompt management with Dex Can do “diversion” surgery to reroute CSF Associated with some risk factors including: • personal / FH of brain / leukaemia / sarcoma / early onset breast Ca • Prior therapeutic CNS irradiation • NF type 1 & 2 • TS type 1 & 2 S&S: < 5 years: Persistent / recurrent vomiting Abnormal balance / coordination / gait Abnormal eye movements Behaviour change (esp. lethargy) Afebrile fits Abnormal head position – twist / tilt 5-11 years: Above + Blurred / double vision Headache 12-18 years Above + Delayed /arrested puberty Central tumours (e.g. pilocytic astrocytoma) Affect visual system & hypothalamus Can obstruct CSF drainage à hydrocephalus & raised ICP Symptoms include: headache, abnormal eye movements, papilloedema, decreased visual acuity, vomiting, DI, fits, CN palsies, roving eye movements (occur if loss of vision à failure of fixation), new nystagmus, hypothalamus involvements Brain Stem tumours (e.g. brain stem glioma) Lower cranial nerve palsies (dysphagia) and ipsilateral motor signs (distruption of corticospinal tracts) Symptoms include: gait disturbance, headache, CN palsies, pyramidal signs, squint and facial palsy Posterior Fossa tumour (e.g. medulloblastoma) Raised ICP à headache, nausea & vomiting especially in the mornings Gait problems, papilloedema, eye movement disturbance, nystagmus and squint Supratentorial mass (e.g. low grade glioma) Focal signs – weakness and focal seizures Raised ICP Low Grade Glioma (45%) = most common. Subdivided to types Astrocytomas: Most common brain Ca in children (40%). Anywhere in brain / cord. Most common in cerebellum. Usually slow growing. Most common in 5-8yrs. Aim to resect Brain stem: almost exclusive to children of school age (mean = 6yrs) but can grow large before symptomatic. Radiation & chemo, position makes inoperable. Mostly are diffuse but 20% are focal. Usually 6m of symptoms before diagnosis. Most children die within 1yr of diagnosis Ependymomas: (10% of paed brain Ca) lining of ventricles / cord. Most common in cerebellum à blocks CSF. Usually < 10yrs old, 30% are < 3yrs. 50% 5yr survival Optic nerve glioma: most common with neurofibromatosis. Primative Neuro-ectodermal tumours (PNETs) (25%) CSF borne mets in 10-15% Excise + radio (+/- chemo) 70% of local cases à cure Arise from embryonic neural crest. On Scans… Gliomas = mainly diffuse Medulloblatsoma = midline cerebellum Can be located in soft tissue or bone Most commonly present in chest Peak 5yrs Medulloblastoma: (20% paed brain Ca) fast growing B>G. Mostly occur < 10yrs old Almost always in midline of posterior fossa Cause raised ICP & ataxia Often met to other parts of brain esp. cord (seed via CSF) – 20% have spinal mets at diagnosis 50% 5yr survival after resection & radiotherapy Supratentorial (pineoblastomas) = worse prognosis Ependymoma (10%) In / around ventricles Causes obstructive hydrocephalus Treat with surgical excision fb radiotherapy à 70% survival Craniopharyngioma (5%) Slow growing, midline epithelial tumours From remnants of rathke’s pouch (suprasellar) Usually benign around pituitary. Rx – Difficult to treat due to location – try resection CNS germ cell tumours (5%) Gorlin Syndrome a.k.a nevoid basal cell carcinoma syn AD on Chr 9 Skin – early BCC Eyes – cataracts, glaucoma, coloboma, strabismus, blindness CNS – falx calcification, fits, mental retardation, partial agenesis of corpus callosum, hydrocephalus, nerve deafness, MEDULLOBLASTOMA Endocrine – hypogonadism + absent / undescended testis Bones – anomalies to ribs, spina bifida & kyphoscolisos Rx: control ICP, tumour resection, chemo/radiotherapy Spinal Tumours Rare S&S: back pain @ night, gait disturbance, problems with sphincter control Most commonly astrocytomas or ependymomas OR cord compression from non-neural tumours e.g. neuroblastoma, lymphoma or Ewings Neuroblastoma 7% of childhood malignancy Commonest extra-cranial solid tumour in children Malignant embryonal tumours from neural crest = sympathetic neuroblasts Can produce Adrenaline & NA (90-95%) à break down products in urine. E.g. VMA / HVA = marker for diagnosis & monitoring response to Rx Median onset 2yrs, ½ present <2yrs, rare > 5yrs, Majority = adrenals / abdo / thorax (relate to sympathetic chain) Assoc with – NF1 & hirschsprungs Presentation = non-specific / site dependent Often advanced at diagnosis with mets to bone/marrow/liver/CNS/lungs LN / palpable mass Thoracic – horners / airway compression (wheeze) Neuro – heterochromia iridis, myoclonus with rapid eye movements Skin – raised bluish non-tender nodules Bone mets – pain, proptosis, racoon eyes (periorbital bruising) Marrow – pancytopenia GIT – diarrhoea (secondary to VIP secretion) Calcification on AXR should always à suspicion Nosebleeds – if olfactory neuroblastomas & due to thrombocytopenia from marrow infiltration Sweating / pallor / watery diarrhoea & raised BP Sites S&S: Ix: Staging 50% adrenal medulla 25% abdominal sympathetic ganglia 5% pelvis 20% chest 5% neck (can have Horner’s) } } } 80% in abdomen Miserable, FTT, pallor, Extensive bruising inc. periorbital (mimics NIA) Limb pain – focal bony tenderness Proptosis, paraplegia, usually in abdo but can be in thorax, neck or head, mediastinal compression, skin nodules, hepatomegaly. Can cause Horner’s syn / cord compression presence of mass VMA & HVA in urine, marrow / tumour biopsy Increased urine catecholamines 1 – Confined to origin 2 – Spread outside origin but not across midline a. Without LN involvement b. With LN involvement 3 – Spread beyond midline 4 – Disseminated (20-30% 5 yr survival) o 4s – Small adrenal 1 with mets limited to skin, liver, marrow. Can à spontaneous regression. Usually < 1y old Treatment Stage 1 – surgery Stage 4 – induction fb high dose chemo then surgery, then stem cell rescue with radiotherapy Stage 4s – usually resolve spontaneously Mets most commonly to lymph nodes, bone, bone marrow, liver, and skin. 75% have mets at diagnosis Prognosis Better when younger (can be spontaneous regression in neonate) <15% survival in over 1s Better for extra-abdominal sites Better with lower stages (stage 1 = >90%) Poor prognosis - > 1yr, stage 3 or 4, increased tumour markers (ferritin, LDH, neuron-specific enolase), poor histology/genetics (MYCN amplification / 17q gain, 1p loss) Wilms Tumour (Nephroblastoma) 6% of childhood malignancy Tumour of embryonic kidney tissue - One of the commonest solid tumours (Main differential is neuroblastoma) Usually birth-5yrs (peak 2 yrs) - 75% occur < 4 yrs 33% assoc with deletion of Cr 11p13 à 10% bilateral Only 2% have FH Assoc with other congenital abnormality 4% GU 3% hemihypertrophy 1% sporadic aniridia Assoc with syndromes WAGR – Wilms, Aniridia, GU malformations, mental Retardation Denys-Drash – Wilms, nephropathy, GU malformations Beckwith-Wiederman S&S: Visible / palpable painless mass in well child 1/3 have haematuria +/- HTN fever, vomiting, poor appetite abdo mass (90%) Haematuria (30%) abdo pain (20%) HTN. Can get an acquired vW disease picture to blood results Staging & Prognosis Mostly localised, can met to lungs 10% bilateral (= genetic) 1: localised to kidney, completely excised 97% survival 2: beyond kidney, but completely excised 92% survival 3: residual intra-abdominal deposits due to incomplete excision or spill 87% 4: spread to liver/lung/bone/brain 73% survival 5: bilateral kidneys Mx – short course chemo à surgery, fb chemo (based on histology) & radiotherapy if incomplete resection Germ cell tumours May be benign or malignant Arise from precursors of sperm & ova – therefore retain ability to differentiate into anything Usually arise in gonads, others occur in midline structures e.g. pineal gland & hypothalamus 2 peaks of incidence <3yrs & puberty Most common is congenital sacrococcygeal teratoma Often secrete AFP or b-HCG = used as tumour markers 90% chance of cure Bone Tumours (see rheum notes for more details) Most commonly osetosarcoma or Ewing Presentation with local swelling, pain & occasional path # Osteosarcoma / Ewings Bone tumour = rare (4% of paed malignancy) Incidence increases with age, Peak @ teens – early adulthood Need management at specialist centre Genetic predisposition (FH + assoc with retinoblastoma) Features Typical Hx is minor injury à pain & swelling at metaphysial area Pain, swelling, path #s Osteosarcoma Commonest 1o bone tumour = long bones (around knee in 80%) otherwise in proximal humerus ¼ will have mets at diagnosis 10% met to lungs at Diagnosis 70% survival if no mets < 20% survival if mets Ewing’s = axial skeleton (mainly pelvis), 25% met to bone marrow at presentation Usually <10yrs Ix: X-ray shows sclerotic bone destruction, periosteal elevation (codman’s triangle) with “sunburst” appearance due to soft tissue involvement Management – Surgery (often amputation) +/- radiotherapy (can include extra corporeal bone irradiation) Prognosis = 60% survival (overall), worse in large 1o, axial, mets or poor chemo response Hepatoblastoma Embryonic tumour, <3yrs old Assoc with hemihypertrophy & FH Ca Can à anorexia, abdo mass & jaundice Hepatocellular Carcinoma Assoc with cirrhosis and alpha-1-antitrypsin deficiency, Rx: treat with resection & chemo, consider transplant Retinoblastoma 1/18000 Rb1 gene in CH 13 60% unilateral (spontaneous mutation) 40% bilateral (hereditary Rb gene = 13q14 = thought to be AD with variable penetrance) – but only 10% will have FH è Increased risk of osteosarcoma in 30s Sporadic = later onset and unilateral Survivors (of familial) have higher risk of other Ca (most commonly osteosarcoma) Knudson 2 hit hypothesis 1st hit = germline } in familial form nd 2 hit = somatic } Presentation <2yrs with white pupil S&S: white pupil, strabismus, painful red-eye, poor vision Rhabdomyosarcoma Commonest soft tissue sarcoma. Most occur < 10yrs Rapid growing small round cell tumour of early childhood Features – usually bladder / pelvis / nasopharynx / parameningeal / paratestes. Can have mass, pain or bladder outflow obstruction Mets are rare (lungs, liver & bone & assoc with poor prognosis) Mx – 6-9 courses of combination chemo Prognosis – 10% of bony mets, 70% if paratesticular & fully excised. If relapse = very poor Niesidioblastosis B cell endocrine benign hyperplasia è Low BMs & high insulin è Rx pancreatectomy Mediastinal Masses Anterior Malignant – T-cell NHL, ALL, Hodgkin’s, Malignant germ cell tumour, rhabdomycosarcoma, Ewing’s sarcoma Benign – teratoma, cystic hygroma, haemangioma, thymic cyst Posterior Malignant – neuroblastoma, ganglioneuroblastoma, sarcoma, phaeochromocytoma Benign – ganglioneuroma, Schwann-cell tumour, neurofibroma, bronchogenic cyst Stem cell transplants Autologous = patients own – used for solid tumours Syngenetic = twin Allogenic = sib / related / unrelated – used in leukaemia Give chemo +/- total body irradiation to kill native haemopoetic cells Complications Graft rejection Infection – esp CMV, PCP, fungus GVHD – give tacrolimus / ciclosporin Veno-occulsive disease of the liver (due to chemo drugs) Side effects of ONC drugs Ciclosporin – Hypertrichosis, Gingival Hypertrophy, Tremor, HTN, Renal toxic, Hepatotoxic Cyclophoshpamide à Haemorrhagic cystitis (can be prevented with high fluid intake and admin of mesna) L-Asparaginase à Deranged Clotting, hepatotoxic, pancreatitis, hyperglycaemia Amphoteracin B à Hypokalaemia, deranged K & PO4 (nephrotoxic) Methotrexate à mucositis, hepatitis, dermatitis, osteoporosis Doxorubicin à cardiomyopathy, alopecia, mucositis Bleomycin à pulmonary fibrosis Vincristine à neuropathy Cytosine arabinoside à cerebellar toxicity Ondansetron à headache, chest pain Domperidone à acute dystonic reaction Metoclopromide à dystonic reactions (more common than domperidone) Ganciclovir à headache, seizures, hypertension, rash, photophobia, nephrotoxic Ceftriaxone à rash, eosinophilia, biliary sludging Vancomycin à flushing (redman syndrome)