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Late effects of treatment for childhood cancer PowerPoint Presentation

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Description : Check out this medical presentation on Childhood Cancer, which is titled "Late effects of treatment for childhood cancer", to know about childhood cancer, its risk factors, its management, etc.

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Published on : May 13, 2021 | Views : 1614 | Downloads : 1

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Slide 1-

Late effects of treatment for childhood cancer
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1950 – 1960 5 years EFS – 20% >1990 - 70% >2000- 80% Approximately 1 of every 640 individuals in US between ages of 20 and 39 years is survivor of childhood cancer 10 cancer survivors/100,000 healthy children/year
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Children Cancer Survivor Study (CCSS) >20,000 survivors at least 5 years, treated from 1970 to 1986 (CCSS) - standarized mortality rate (SMR) =10,8 SMR higher in women SMR higher in survivors treated <5years of age SMR highest in children treated for: CNS tumors and acute leukemias
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Causes of death Cancer recurrence/ second neoplasm SMR =19.4 Pulmotoxicity SMR = 9.2 Cardiotoxicity SMR = 8.2 infections
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Secondary malignancy Standarized incidence ratio (SIR) is 6.38 for the largest observed excesses for bone (SIR=19.1) and breast cancer (SIR=16.2) a 10-fold - for subsequent CNS cancer and thyroid cancer The cumulative incidence of SMN 20 years from the time of original cancer diagnosis is 3.2% overall and varied by diagnostic subgroups: - Hodgkin lymphoma - 7.6% - soft-tissue sarcoma - 4.0% - bone sarcoma - 3.3%
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Risk factors: Primary neoplasm (retinoblastoma, HL, STS) Younger age at the time of therapy Female sex Radiotherapy Chemotherapy (alkylating agents, topoizomerase inhibitors) Genetic predisposition ( Li-Fraumeni syndrome, NF t.1, Fanconi anemia, gene polimorphisme) enviroment
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Hodgkin lymphoma >ALL, ANLL, CML, bone tumors, thyroid cancer, breast/ skin cancer Retinoblastoma > osteosarcoma Nephroblastoma (genetic form) >osteochondroma, adenocarcinoma T-ALL > ANLL Radiotherapy > osteosarcoma, STS, skin cancer Radiotherapy of neck > thyroid cancer
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Management Patient education Detailed history, including family history Careful clinical examination Advice on reduction risk behaviours, especially smoking and sunbathing
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Circulatory system Anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin, mitoxantrone) , cyclophosphamide - myocytes damage due to free radicals generation Thoracic radiation therapy - affected fine vasculature of the heart
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The risks to the heart are related to: - Cumulative anthracycline dose: >200-300mg/m2 >600mg/m2 > 30% 500- 600mg/m2 > 11% - method of administration (bolus) - younger age (<15years of age) - female sex - trisomy 21
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and in addition: - hypothyroidism - ovarian failure - obesity - renal failure - hyperlipidemia - pulmonary failure - pregnancy - cong.heart disease - growth hormone therapy - sex steroid replacement therapy
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Cardiomyopathy Early: at the time of treatment to 1 year after the treatment Late: > 1 year after treatment
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Thoracic radiation therapy >15Gy Delayed pericarditis Pancarditis, which includes pericardial and myocardial fibrosis, with or without endocardial fibroelastosis Myopathy Coronary artery disease (CAD) Functional valve injury Conduction defects
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Signs and symptoms Cardiomyopathy (after chemotherapy): fatigue, cough,dyspnea on exertion, peripheral edema, hypertension, tachypnea/rales, tachycardia, cardiomegaly, syncope, palpitations, arrhytmias Valvular damage (after radiation therapy >40Gy): weakness,cough, dyspnea on exertion, new murmur Pericardial damage ( radiation >35 Gy) : fatigue, dyspnea on exertion, chest pain, cyanosis, ascites, peripheral edema, hypotension, friction rub, muffled heart sounds, venous distension, pulsus paradoxus Coronary artery disease (radiation > 30Gy): chest pain on exertion, dyspnea, diaphoresis, pallor, arrhytmias
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Diagnosis Electrocardiogram (ST-T changes voltage, decreased voltage) Chest x-ray Holter monitoring Exercise testing baseline Echocardiogram ( lower % EF, shortening fraction <28%, higher afterload)
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Indications Abnormal clinical examination & abnormal echocardiogram & planning sport & before pregnancy : ->cardiologist consultation Treatment angiotensin converting enzyme inhibitors cardiac transplantation
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Respitatory system Radiation therapy >15 Gy (whole lungs, mediastinal, mantle, TBI): Pneumonitis acute (>40 Gy alone - or lower dose + dactynomycin/ anthracyclines ) signs: fever, congestion, cough, dyspnea 12 – 14 Gy – reduced total lung capacity and vital capacity to about 70% Pulmonary fibrotic disease with permanent restrictive disease
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Chemotherapy: Bleomycine >200mg/m2 busulphan Lomustine, carmustine, cyclophosphamide
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Signs and symptoms Fatigue Cough dyspnea on exertion reduced exercise tolerance Orthopnea Cyanosis finger clubbing Rale cor pulmonare
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Screening and diagnostic tests Baseline chest x-ray O2 saturation Pulmonary function test
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Management and intervention Advice against smoking Pneumococcal immunisation Annual influenze immunisation in patients with etablished lung disease
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Urinary system Renal failure due to: Disease: nephroblastoma, NHL, leukemia > > renal infiltration > blood vessels compression > hypertension
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Chemotherapy: Cisplatin ,carboplatin -> glomerular dysfunction - Asymptomatic or fatigue, anemia, oliguria cisplatin, carbo, ifosfamide -> tubular dysfunction - seizures (low Magnesium!), weakness (low PO4), glikozuria, poor linear growth ifosfamide -> glomerular and tubular toxicity with renal acidosis and Fanconi’s syndrome cyclophosphamide, ifosfamid ->hemorrhagic cystitis - Hematuria, dysuria
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Radiotherapy Doses > 25 Gy to both kidneys > renal failure at delayed intervals of more than 6 months Radiation 20 – 30 Gy or 10- 15 Gy with chemotherapy > - hypoplastic kidney/ renal arteriosclerosis: *fatigue, poor linear growth, hypertension, headache, edema, albuminuria - nephrotic syndrome * proteinuria, edema - bladder: fibrosis or hypoplasia (reduced bladder capacity) *urgency, frequency, incontinence (nocturia), pelvic hypoplasia - bladder tenderness *urinary tract infections, renal calculi
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Management and intervention In dependence of late effect: Glomerular dysfunction, hypoplastic kidney - low-protein diet, dialysis, renal transplant Tubular dysfunction - Mg supplement, PO4 supplement Nephrotic syndrome - low salt diet, diuretics
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Gastrointestinal tract Enteritis due to: Chemotherapy (actinomycin D, doxorubicin) Radiation >40Gy Surgery (abdominal surgery enchance RT effect) - abdominal pain - diarrhea, decreased stool bulk - emesis - weigth loss, poor linear growth
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Adhesions due to: Radiation Surgery -abdominal pain - bilious vomiting - hyperactive bowel sounds Indications: * abdominal radiograph * adhesion lysis
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Fibrosis esophagus (stricture) due to: Chemotherapy (actinomycine D, doxorubicine) Radiation >50 –50 Gy Abdominal surgery - weight loss - dysphagia - poor linear growth Indications: * esophagus dilatation * Antireflux therapy
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Fibrosis small intestine due to: Radiation > 40 Gy Abdominal surgery - diarrhea - weight loss - obstruction - abdominal pain - constipation Indications: *high –fiber diet *decompression, resection, balloon dilatation
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Large intestine/ colon fibrosis due to: Radiation >40 Gy Abdominal surgery Signs: - abdominal colic - rectal pain - constipation - melena - weight loss - obstruction Indications: * stool softeners, high-fiber diet
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Hepatic late effects Fibrosis/ cirrhosis due to: Chemotherapy ( mtx, act D, 6-MP, 6-TG) Radiation >30 Gy Surgery Hepatitis B/C infection
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Endocrine system Thyroid late effects Overt hypothyroidism - radiation >20 Gy to the neck, cervical spine - TBI - partial or total thyroidectomy Symptoms: hoarseness, fatigue, weight gain, cold intolerance, dry brittle hairs, alopecia, constipation, lethargy, pubertal delay, bradycardia, hypotension Diagnosis: T4, TSH
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Compensated hypothyroidism- asymptomatic Hyperthyroidism –nervousness, tremor, heat intolerance, weight loss,increased apppetite, insomnia, diarrhea, moist skin, goiter Thyroid nodules – any dose radiation hoarseness, fatigue, dry skin, cold intolerance, dry brittle hair, alopecia, constipation, lethargy, poor linear growth Biopsy!
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Neuroendocrine late effects GH deficiency - Radiation >24 Gy - Surgery (tumor in region of H-P axis) Adrenocorticotropic hormone deficiency - Radiation >40 Gy/ surgery Thyrotropin-releasing hormone deficiency - Radiation > 40 Gy Precocious puberty - Radiation >20 Gy
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Gonadotropin deficiency - Radiation >40 Gy/ surgery Hyperprolactinemia - Radiation >40 Gy/surgery Metabolic syndrome: (insulin resistance, hyperglycemia, hyperinsulinemia, hypertension, hyperlipidemia, obesity): - steroids - radiation ? >18 Gy
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Musculoskeletal system Radiation therapy> 20 Gy : > soft tissue hypoplasia > assymmetry of muscle mass when compared with untreated area,decreased range of motion, stiffness and pain in affected area > spinal abnormalities : scoliosis, kyfosis, lordosis, decreased sitting height > back pain, hip pain, uneven shoulder height, rib humps or flares, deviation from vertical curve, gait abnormalities
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diminution of bone growth > lenght discrepancy: lower back pain, limp,hip pain, discrepancy in muscle mass and length when compared with untreated extremity, scoliosis > pathological fracture >osteonecrosis (steroids, radiation >40Gy): pain in affected joint, limp >osteopenia/ osteoporosis (steroids,radiation >18 Gy)
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Obesity Risk factors: Female survivors ALL CNS radiation Steroids Cranial irradiation Genetic predisposition Polimorphism in the leptin receptor gene Brain tumors (hypothalamic dysfunction)
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Reproductive system Male gonadal function: Germ cell damage (oligospermia/azoospermia) Chemotherapy: cyclophosphamide, lomustine, carmustine, procarbazine, ifosfamide, busulfan, melphalan,dacarbazine Radiation >1 Gy Surgery (orchiectomy or surgical manipulation) * Symptoms: testicular atrophy * Diagnosis: FSH, inhibin B, spermiogram * Management: sperm banking prior to treatment
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Leydig cell damage: Chemotherapy: cyclophosphamide, etoposide Radiation> 12 Gy to the testes or scattered from pelvis Surgery: orchiectomy *Symptoms: delayed/arrested/absent pubertal development, lack of penile and testicular enlargement, voice change, body odor and acne, testicular atrophy * Diagnosis: LH, testosterone * Management: testosterone replacement regarding testosterone deficiency
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Female gonadal late effects Ovarian failure: Chemotherapy (cyclophosphamide,procarbazine, busulfan,melphalan, dacarbazine, carmustine, ifosfamide) Radiation >4 Gy Surgery: oophorectomy or oophoropexy *Symptoms: delayed/arrested pubertal development (breasts, female habitus, menses, estrogen deficiency, infertility), osteoporosis, atherosclerosis *Diagnosis: LH,FSH, inhibin B, anti-mullerian hormone *Management: hormone replacement
Slide 42-

Vagina: fibrosis/diminished growth Chemo: act D, doxo – enhance radiation therapy effect Radiation >40Gy Uterus: Radiation >20 Gy (prepubertal), >40 Gy (pubertal) *Symptoms: spontaneous abortions, low birth-weight infants, small uterus *Diagnosis: usg
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Growth impairment Brain tumors (craniopharyngioma) Cranial radiotherapy > GH deficiency (>24 Gy) LH/ FSH/ ACTH/ TSH deficiency (>40 Gy) Spinal irradiation > spinal growth is affected > skeletal disproportion Radiation directed on the gonads TBI Precocious puberty after cranial irradiation Chemotherapy, steroids
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Monitoring for growth problems Regular height measurement Endocrinologist consultation Treatment with growth hormone Craniopharyngioma After cranial iradiation (acute leukemia) – possibility of cancer recurrence??? - second cancers?
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CNS late effects Neurocognitive deficits (after radiation >18Gy, HD MTX) -difficulty with: reading, language, memory, attention, decreased IQ, poor school attendance, poor hand-eye coordination Leuko-encephalopathy (MTX, Ara-C, radiation >18 Gy) -seizures, neurologic impairment Focal necrosis (MTX,cisplatin, carmustine, radiation >50 Gy) -headaches, seizures, papilledema, hemiparesis, speech/learning/memory deficits
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Large vessel stroke (radiation >50 Gy) -headache, seizures, hemiparesis, aphasia, focal neurologic findings Vision loss (cisplatin, radiation >50 Gy, surgery) -progressive visual loss Ototoxicity (cisplatin, carboplatin, radiation >35 Gy, surgery) - abnormal speech development, hearning Myelitis (radiation >45 Gy, surgery) -paresis, spasticity, altered sensation, loss of sphincter control
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Ear late effects Chronic otitis (radiation >35 Gy) Sensorineural hearing loss (cisplatin, carboplatin, radiation >40 Gy) Decreased production of cerumen (radiation >30 Gy) Chondritis ( radiation 50 Gy) Chondronecrosis (radiation 60 Gy)
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Eye late effects Radiation >50 Gy: Decreased tear production Lacrimal duct fibrosis Ulceration of eyelids Conjunctiva: necrosis, scarring Thinning of aclera Cornea ulceration Neovascularization keratinization
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Cataract Secondary glaucoma Iris neovascularization Retina: infarction, exudates, hemorrhage, teleangiectasia, neovascularization, macular edema, optic neuropathy
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Dental late effects Xerostomia (decreased salivary gland function) due to radiation >40 gy Abnormal tooth and root development due to radiation >10 Gy and chemotherapy