1 / 36

Jacek Wachowiak

Jacek Wachowiak. COMPLICATIONS OF CHEMO- AND RADIOTHERAPY IN CHILDREN WITH CANCER. STANDARDS OF CONTEMPORARY CANCER TREATMENT. Early diagnosis Start of treatment as soon as possible after diagnosis Complex interdisciplinary treatment : > chemotherapy (CT) > HSCT

ornice
Download Presentation

Jacek Wachowiak

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Jacek Wachowiak COMPLICATIONS OF CHEMO- AND RADIOTHERAPY IN CHILDREN WITH CANCER

  2. STANDARDS OF CONTEMPORARYCANCER TREATMENT • Early diagnosis • Start of treatment as soon as possible after diagnosis • Complex interdisciplinary treatment : > chemotherapy (CT) > HSCT > radiotherapy ( RT ) > immunotherapy > surgery > target therapy • Treatment exclusively in properly experienced and equiped centers

  3. CANONS OF CONTEMPORARY CHEMO- AND RADIOTHERAPY OF CANCER • Mobilization and synchronization • Multiagent • Periodicity • Long duration • Use of maximal tolerated doses of cytostatics and irradiation • Selective destroy of cancer tissue with minimal and reversible damage of healthy tissues • Prophylaxis of complications of chemotherapy and radiotherapy • Supportive care

  4. TISSUE MOST ENDANGERED TO GENERAL AND SELECTIVE TOXICITY OF CHEMOTHERAPY AND RADIOTHERAPY • GENERAL TOXICITY > tissue demonstrating high proliferative activity - hematopoietic tissue - lymphopoietic tissue - epithelial tissue > germinal cells • SELECTIVE TOXICITY > cardiac toxicity ( anthracyklines ) > hepatotoxicity ( antimetabolities, RT ) > renal toxicity ( cisplatin, RT ) > pulmonary toxicity ( busulfan, bleomycin, RT ) > neurotoxicity ( vincristin, RT ) > epiphyseal cartilage ( RT )

  5. CHEMOTHERAPY & RADIOTHERAPYOF CANCER IN CHILDREN 1. early side effects and complications 2. delayed consequences

  6. EARLY COMPLICATIONSOF CANCER CHEMOTHERAPY & RADIOTHERAPYIN CHILDREN

  7. EARLY COMPLICATIONSOF CANCER CHEMOTHERAPY & RADIOTHERAPYIN CHILDREN I. tissue and organ toxic injury II. compromized cellular and humoral immunity and alteration of mucosal and skin barriers

  8. EARLY COMPLICATIONS OFCANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN I. TISSUE AND ORGAN TOXICITY • myelosupression • immunosupression • oral mucositis and gastrointestinal mucosa damage • nausea, vomiting and anorexia • hepatic toxicity • skin toxicity • renal toxicity • bladder toxicity • peripheral and central neurotoxicity • ototoxicity • cardiac toxicity • pulmonary toxicity

  9. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • MYELOSUPRESSION > LABORATORY EXPOTENTS - leuko-, neutro- and monocytopenia - thrombocytopenia - decreased number of retikulocytes - decreased bone marrow cellularity > CONSEQUENCES - infections ( mainly bacterial and fungal ) - diathesis haemorrhagica and bleedings - anemia

  10. MONITORING, PROPHYLAXIS AND THERAPY OF CONSEQUENCES OF MYELOSUPRESSION • blood cell count control • therapy modification according to WBC, and thrombocytes counts • thromocytopenia # platelets concentrate transfusions ( platelet count < 20 x 109 / L ) # rekombinated thrombopoetin • anemia # erythrocytes transfusions ( Hb < 7 g% ) # rekombinated erythropoetin WARNING ! All blood products should be leukocyte depleted, screened viral infection and irradiated (24-30 Gy) • granulocytopenia (<0.5 x 109 / L ) # infections prophylaxis, monitoring and treatment

  11. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • IMMUNOSUPRESSION > LABORATORY EXPOTENTS - lymphopenia; - hipogammaglobulinemia; > CONSEQUENCES - increased risk of infections, especially viral, fungal and protozoal; > MONITORING, PROPHYLAXIS AND TREATMENT OF CONSQUENCES OF IMMUNOSUPRESSION - monitoring of electrophoresis and immunoelectrophoresis; - prophylaxis and treatment (7S-polyvalent intravenous immunoglobulins, anti-viral drugs, anti-fungal drugs, anti- protozoal drugs);

  12. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN- INFECTIONS AND THEIR SPECTRUM IN RELATION TO THE TYPE OF DEFICIT IN PATIENTS DEFENSES (PART A) • neutropenia - Gram - positive bacteria - Gram - negative bacteria - fungi (Candida spp., Aspergillus spp., Mucor spp.) • lymphopenia # lymphocytes T - Herpes viruses (VZV, HSV, CMV, EBV) - Pneumocystis carinii # lymphocytes B - encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis)

  13. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN - INFECTIONS AND THEIR SPECTRUM IN RELATION TO THE TYPE OF DEFICIT IN PATIENTS DEFENSES (PART B) • decreased number of monocytes and tissue macrophages - monocytes presents antigens to lymphocytes and create a main source of inflammatory cytokines; therefore monocytes are important in the host’s defence against viral, fungal and protozoal infections - monocytes are especially important in responding to bacteria (Salmonella, Mycobacteria, Brucella, Listeria) and fungi (Candida spp., Histoplasma), which act as intracellular parasites • damaged mucosal and skin barriers - endogenous bacteria

  14. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • TOXIC INJURY OF ORAL AND GASTROINTESTINAL MUCOSA > CLINICAL SYMPTOMS - stomatitis with ulceration and pain - abdominal pain, watery stools not related to infection, hemorrhagic stools > CONSEQUENCES - infections (mainly with opportunistic endogenous microflora) - bleedings - perforation - worsening of general status

  15. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • NAUSEA AND VOMITING > PATOGENESIS - 5HT released under the influence of cytostatics from enterochromafin cells of stomach and gut, activates its receptors and initiates fibers depolarization of vagus nerve (n. X) > CONSEQUENCES - difficulties with oral drugs administration and oral feeding - exacerbation toxic injury of the mucosa in oral cavity, pharynx and esophagus - releuctance to treatment continuation

  16. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • NAUSEA AND VOMITING PROPHYLAXIS > antagonists of 5HT receptor (ondansetron - Zofran, tropisetron - Navoban, granisetron - Kytril)

  17. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • HEPATOTOXICITY > HEPATOTOXIC FACTORS - antimetabolities ( methotrexate, merkaptopurin, thioguanin, cytarabine ) - actinomycin D - radiotherapy - other factors ( viral infections - HCV, HBV, CMV, EBV; antiviral drugs, amphotericin, long period of parenteral nutrition ) > CONSEQUENCES - hepatic dysfunction with increased bilirubin level, liver enzymes activity with subsequent liver fibrosis and insufficiency

  18. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • HEPATOTOXICITY > SURVEILLANCE - serum bilirubin, AlAt, AspAt, GGTP, NH3, electrophoresis, PTT - liver USG - biopsy and immunohistopathology (if necessary) > PROPHYLAXIS - dose of cytostatics atapted to current liver function - prevention measueres against infection with hepatotropic viruses (HBV, HCV)

  19. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • CARDIAC TOXICITY > CARDIOTOXIC FACTORS - anthracyclines (daunorubicin, adriamycin ) > CONSEQUENCES - unspecific arrhythmias (acute toxicity shortly after the administration)

  20. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • CARDIAC TOXICITY > SURVEILLANCE - EKG, ECHO, CK, AspAt and LHD activity in serum > PREVENTION - cumulative dose of doxorubicin below 550 mg/m2, - cumulative dose of daunorubicin below 600 mg/m2 - cumulative dose of adriamycin below 450 mg/m2 - correct way of administration (duration, concentration, period betwen subsequent doses) - administration of dexrazoxane ( Cardioxane )

  21. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • BLADDER TOXICITY > PATOGENESIS - akrolein ( urotoxic metabolite of cyclophosphamide, which induce hemorrhagic cystitis) > SYMPTOMS - dysuria - urgency - erythrocytes and clots in urine

  22. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN > PREVENTION OF HEMORHHAGIC CYSTITIS - intensive i.v. hydratation ( 3000 ml /m2 ) - diuresis stimulation - mesna ( Uromitexan ) at the dose of 160% the dose of cyclophospamide – binds acrolein

  23. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • RENAL TOXICITY > ANTINEOPLASTIC AGENTS ASSOCIATED WITH NEPHROTOXICITY - cisplatin - methotexate > PATOGENESIS - necrosis of proximal and distal renal tubules >CONSEQUENCES - renal insufficency

  24. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • RENAL TOXICITY > SURVEILLANCE - concentration of urea and creatinin in serum and in urine - ccreatinine clearance; - cisplatin; beta 2-microglobuline in urine; GGTP - GGTP, leucinaminopeptidse, alaninaminopeptidse and Mg in serum ; - metotrexate – monitoring of drug concentration in blood; > PREVENTION - cisplatin – administration of magnesium sulphate, mannitol for diuresis induction and hyperhydratation; - metotrexate – hyperhydratation, diuretics,urine alkalization;

  25. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • TUMOR LYSIS SYNDROME (TLS) > PATOGENESIS - hyperuricemia, hyperphosphatemia, hyperkaliemia and symptomatic hypocalcemia resulted from death of numerous tumor cells and release of their contents into the circulation; - cristalization uremic acid in renal tubules;

  26. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • TUMOR LYSIS SYNDROME (TLS) > PREVENTION AND THERAPY - hyperhydratation ( 3000 ml/m2 / 24 h ) - urine alkalization pH > 7,0 ( 8,4% Natrii bicarbonici ) - diuretics - uric acid reduction (allopurinol or urate oxidase) - correction of electrolyte disturbances - dialysis when : volume overload, hyperkaliemia, hyperphosphatemia, hyperuricaemia, symptomatic hypocalcemia, renal failure - recombinated uric oxydase (conversion of uric acid to soluble allantoin) - Rasburicase

  27. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • PERIPHERAL NERVOUS SYSTEM TOXICITY - Vinca alkaloids( vincristin, vinblastin ) - symptoms : # loos of deep tendon reflexes # neuritic pain # paresthesias # wrist and foot drop # urinary retention # paralytic ileus – most dangerous !!!

  28. EARLY COMPLICATIONS OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • CENTRAL NERVOUS SYSTEM TOXICITY > metotrexate ith. +/- CNS radiotherapy - meningeal irritation or arachnoiditis with severe headache, stiff neck, vomiting, lethargy, trancient or permanent paraplegia, fever, and inflammatory pleocytosis in the CSF;

  29. LATE COMPLICATIONSOF CANCER CHEMOTHERAPY & RADIOTHERAPYIN CHILDREN

  30. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • impaired linear growth and development • impaired gonadal development and reproductions aberrations • disruption of function in other organ systems: - CNS (neurologic, intellectual and psychosocial sequelaes) - liver - kidney - heart - lungs - pancreas - gastrointestinal tract - skeleton • genetic aberrations, oncogenesis, teratogenesis

  31. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • impaired linear growth and development > systemic causes - growth hormone (GH) deficiency - thyroid hypofunction - corticosteroids administration - malnutrition related to chronic disease and treatment > local factors - radiotherapy (dose related impaired growth of bones and joints due to growth plates injury and deficient blood supply related to vessels sclerosis)

  32. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • GONADAL FUNCTION IMPAIRMENT > gonadotoxic factors - alkylating agents, methotrexate, doxorubicin, vincristin, vinblastin - radiotherapy > boys / men - Leydig cell hypofunction (low testosterone blood levels) - azoospermia lub oligospermia (infertility) > girls / women - premature menopause, infertility > hormonal substitution

  33. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • CENTRAL NERVOUS SYSTEM LESIONS > radiotherapy, methotrexate ith., cytarabine ith. > leucoencephalopathy > intellectual regression > psychological anomalies > neurological local symptoms > seizures • LIVER > antimetabolities (methotrexate, mercaptopurine) +/- irradiation > veno-occlusive disease with subsequent chronic dysfunction and liver cirrhosis

  34. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • HEART > radiotherapy > 45 Gy > anthracyclines (adriamycin > 450 mg/m2, doxorubicin > 550 mg/m2, daunorubicin 600 mg/m2) > congestive heart failure (CHF) with arrhytmia and sudden death • LUNGS > bleomycin, alkylating agents and irradiation > lung fibrosis with restrictive impairment of ventilation

  35. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • URINARY TRACT > irradiation > 15-20 Gy hypertension +/- late renal failure > cisplatin ; persistent injury of renal tubules with renal failure > cyclophosphamide, ifosfamide ; fibrosis of bladder wall

  36. DELAYED CONSEQUENCES OF CANCER CHEMOTHERAPY & RADIOTHERAPY IN CHILDREN • SECONDARY MALIGNANCY > in 0,95% of children with acute leukemias 15 years from treatment cessation > in 5,1% of children with Hodgkin’s disease 20 years after treatment cessation

More Related