Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
SlideShare a Scribd company logo

Onco emergencies : DR. DEVAWRAT BUCHE

•Download as PPTX, PDF•
•
Devawrat Buche
Devawrat Buche

This document discusses oncological emergencies, including tumor lysis syndrome, malignant hypercalcemia, superior vena cava syndrome, and others. It provides details on the definitions, causes, clinical presentations, diagnostic criteria, and treatment approaches for these time-sensitive cancer complications. Tumor lysis syndrome can result from cell lysis releasing uric acid and electrolytes, and requires aggressive hydration, allopurinol or rasburicase, and renal replacement therapy if severe. Malignant hypercalcemia is most common in breast and lung cancers and multiple myeloma, presenting with nausea, fatigue, and neurological symptoms, treated initially with hydration and bisphosphonates. Superior vena cava syndrome ob

1 of 69
ONCOLOGICAL EMERGENCIES Dr. Devawrat Buche, MD
CANCER BURDEN GLOBAL BURDEN • In 2000, burden of new case estimated 10.1 million • 56 % of cancer deaths in developing countries • Lung cancer >> stomach ca > prostate, colorectal ca • Develpoed countries : breast >> colorectal > lung > uterus • Males : lung > stomach> liver > H&N • Females : breast, cervix > stomach> lung > colorectal BURDEN IN INDIA • 2 – 2.5 million cases at a given time • Year 2000 : 8 lakh new cases, 5.5 lakh deaths • Heavy tobacco use : leading cause • 70 % present at advanced stages ( T3 – T4 stages ) : heavy mortality. ( MOHFW and TMH EBM data )
• Any cancer may present itself as an emergency due to :  mass effect ( SVC syndrome, cord compression, leucostasis , gut obstruction etc.) Tumor invasion ( sentinal/ torrential bleed, effusions and tamponade ) Paraneoplastic syndrome ( hypercalcemia, SIADH, etc. ) Chemo induced damage ( heart failure, pancreatitis, severe infections, renal and hepatic failure , etc. )
Considerations before intervention • Is the condition truly emergent ? • malignancy or a benign process ? • Specific tumor type ? • Tumor stage ? • Studies required to establish diagnosis ? • Prognosis and impact of intervention on patient ? • WHAT ARE THE WISHES OF THE PATIENT AND FAMILY ??? Irvin & Rippe, 7th edition
ONCOLOGICAL EMERGENCIES • Tumor lysis syndrome • Malignant hypercalcemia • SVC syndrome • Epidural cord compression • Leucostasis • Malignant pericardial effusion/ tamponade • Chemo induced cardiotoxicity • Others : SIADH /hyponatremia, bleeding, febrile neutropenia, DIC , etc.
1. TUMOR LYSIS SYNDROME • Syndrome of metabolic derangements • Observed in cancers with large tumor burden, high proliferative rates or high chemosensitivity. • Metabolic derangement due to massive cell lysis and outpouring of intracellular chemicals: Hyperuricemia Hyperkalemia Hyperphosphatemia Hypocalcemia uremia
Incidence • most frequently in patients with NHL and other hematologic malignancies,particularly Burkitt’s lymphoma, ALL, and acute myeloid leukemia (AML). • The overall incidence of LTLS and CTLS ranges from • 14%-17% and 3%-5% in AML, • 21%-30% and 5%-8% in ALL, • and 19%-40% and 6%-20% in NHL • solid tumors : occurrences are rare, with a very high mortality ( 1 in 3 )
Risk factors
Classification • currently no universally accepted system for classification and grading. • The most recent and preferred is : Cairo and Bishop classification system • based on defining laboratory or clinical TLS (LTLS or CTLS). • This system distinguishes between patients who do not require therapeutic intervention versus those experiencing life-threatening clinical abnormalities. • LTLS is considered to be either present or absent, • whereas the grade of CTLS is defined by the maximal grade of the clinical manifestation
L -TLS
C -TLS
Clinical manifestations • may occur before the start of chemotherapy • observed more commonly within 12 to 72 hours after the initiation of cytoreductive therapy • nausea, vomiting, diarrhea, • anorexia, • Lethargy, • edema, fluid overload, congestive heart failure, • hematuria, • cardiac dysrhythmias, • seizures, • muscle cramps, tetany, • syncope, and possible sudden death. • Complications can compromise the efficacy or further administration of chemotherapy.
RISK STRATIFICATION
Prevention HIGH RISK PATIENTS • Adequate hydration and urine output are of high importance in preventing TLS • should be admitted to an intensive care unit • rasburicase should be used in the initial management of pediatric patients • Delaying tumor therapy • RRT as required
INTERMEDIATE RISK PATIENTS • hydration, • allopurinol may be used • single dose of rasburicase might also be considered in pediatric patients LOW RISK PATIENTS • watch-and-wait approach
TREATMENT A. HYPERURICEMIA
FLUIDS AND HYDRATION • Aggressive hydration and diuresis are fundamental to the prevention and management • Promotes the excretion of uric acid and phosphate by improving intravascular volume, RBF, and GFR. • Vigorous hydration is recommended for all patients in the intermediate to- high risk groups • Fluid intake should be maintained at approx 1-2 times maintenance, with a urine output of 80 to 100 mL/m2/h ALKALINIZATION • currently not recommended • risk of precipitation of calcium phosphate crystals • only indicated for patients with metabolic acidosis, in which case sodium bicarbonate may be considered based on the standards of the institution.
ALLOPURINOL • competitive inhibitor of xanthine oxidase • Use of allopurinol has been shown to decrease the formation of uric acid and to reduce the incidence of obstructive uropathy DOSE • ORAL : 50 to 100 mg/m2 every 8 hours (maximum dose, 300 mg/m2/d) or 10 mg/kg/d divided every 8 hours (maximum dose, 800 mg/d). • IV : 200 to 400 mg/m2/d in one to three divided doses (maximum dose, 600 mg/d). TIMING • initiated in intermediate risk patients no more than 12 to 24 hours before the start of induction chemotherapy UPTO 3-7 DAYS AFTER CT. • be continued until uric acid levels are normalized, and tumor burden, WBC count, and other laboratory values have returned to low-TLS risk levels
• only prevents the formation of uric acid and does not reduce uric acid produced before the initiation of treatment.  patients with pre-existing severe hyperuricemia (> 7.5 mg/dL), treatment with rasburicase is preferred • Allopurinol can also cause an increase in serum levels and crystal deposition of the purine precursors xanthine and hypoxanthine, which can result in acute obstructive uropathy. • In addition, because allopurinol also reduces the degradation of other purines, particularly 6- mercaptopurine, dose reductions of 50% to 70% of 6-mercaptopurine and/or azathioprine are recommended. • Because allopurinol is excreted by the kidneys, a dose reduction of 50% is recommended in patients with renal insufficiency.
RASBURICASE • Urate oxidase converts uric acid into allantoin, which is five to 10 times more soluble in urine than uric acid • recommended for the treatment of patients with hyperuricemia associated with LTLS or CTLS, or in the initial management of patients considered to be at high risk DOSE • 0.15 to 0.2 mg/kg once daily , as an IV infusion over 30 minutes for 5 days. • However, rasburicase has demonstrated activity even at lower doses and for shorter duration. • Therefore, a dose of 0.10 to 0.2 mg/kg daily, dependent on whether the intention is prevention or treatment may be used TIMING AND DURATION • 1 to 7 days • uric acid levels be monitored regularly
ADR • rare , include anaphylaxis, rash, hemolysis, methemoglobulinemia, fever, neutropenia (with or without fever), respiratory distress, sepsis, and mucositis. • contraindicated in patients with a known G6PD deficiency and in pregnant or lactating females. • rasburicase will cause the degradation of uric acid within blood samples : assay, which is preferably done within 4 hours of collection.
B.HYPERPHOSPHATEMIA Initial treatment: • eliminating phosphate from IV solutions, • maintaining adequate hydration, • administration of phosphate binders. • Aluminum hydroxide 50 to 150 mg/kg/d is administered in divided doses orally or nasogastrically every 6 hours. • Its use should be limited to 1 to 2 days to avoid cumulative aluminum toxicity • other phosphate binders : such as calcium carbonate, sevelamer hydroxide, and lanthanum carbonate For severe hyperphosphatemia, • RRT : hemodialysis, peritoneal dialysis, or continuous venovenous hemofiltration has been used • Phosphate clearance was found to be better with hemodialysis as compared with continuous venovenous hemofiltration or peritoneal dialysis.
TREATMENT OF OTHER DERANGEMENTS
MONITORING DURING TREATMENT • Check laboratory and clinical TLS parameters 4 to 6 hours after the initial administration of chemotherapy. • The TLS parameter consists of :  uric acid,  phosphate,  potassium,  creatinine,  calcium, and  LDH,  fluid input and urine output • Uric acid levels should be re-evaluated 4 hours after administration of rasburicase and every 6 to 8 hours thereafter until resolution of TLS • If TLS has not occurred after 2 days, the likelihood is essentially zero that the patient will experience TLS • Approx 3% require RRT. • Nephro consultation be obtained immediately if :  oliguria or anuria,  if there is persistent or elevated urea (> 150mg/dl), phosphate(>10mg/dl) or potassium levels(>7mmol/L), or life threatening hypocalcemia  in spite of optimal conservative measures
Prognosis • Outcome variable • Solid tumors : high fatality ( upto 36 %)
2.MALIGNANT HYPERCALCEMIA • MOST COMMON • 10-20 % of patients PHYSIOLOGY
• MECHANISMS IN MALIGNANCY : 1. Direct osteolysis by tumor 2. Increased osteoclastic resorption 3. Renal insufficiency PTHrP : Plays a role , elevated in 80 % patients. • Acitivity similar to PTH. • Stimulates osteoblasts  production of RANKL  osteoclasts activation  osteolysis & production of bone derived growth factors ( TGF β, IGF-1)  TUMOR CELL PROLIFERATION AND MORE PRODUCTION OF PTHrP  renal resorption increases in DCT • In some lymphomas, there is raised levels of Vit D metabolites increased gut absorption
Etiology HISTOLOGY % Breast 19-30 Lung 10-35 Multiple myeloma 20-30 H& N 5-24 Renal 17
Clinical presentation • Rapidity determines the severity • Constitutional : nausea, fatigue, lethargy, mental status changes • Reduced extravascular volume : malaise, fatigue, anorexia, polyuria • Decreased NM excitability : reduced NM tone, hyporeflexia • Pyschiatric symptoms :confusion, lethargy, coma • ECG: short QTc, wide QRS, prolonged PR, bradyarr., BBB, CHB
Diagnosis Elevated serum calcium 1. Raised ionized calcium 2. Raised corrected sr. calcium = 0.8 (4 – alb)+ Ca Other lab studies to be done are : PTH levels, BUN, creatinine, phosphate, magnesium, Vit D levels.
Differential diagnoses • Hyperparathyroidism • Milk alkali syndrome • Vit D, Vit A excess • Lithium • Thiazides • TPN
Treatment CALCIUM LEVEL SYMPTOMS THERAPY < 12 mg/dl none Observation, or hydration followed by observation <12 mg/dl present Hydration, BPN 12 – 14 mg/dl present Hydration, BPN > 14 mg/dl present Hydration, BPN >14 mg/dl severe Hydration,loop diuretics, calcitonin, BPN Alternatives : plicamycin, gallium, prednisone, RRT
• Decision to treat depends upon : Patient history Current disease QOL Patient and family wishes 1. HYDRATION • INITIAL THERAPY OF CHOICE • May require upto 3-7 litres/ 24 hrs • Loop diuretics to be used ONLY if CHF is a concern • IF DIURETICS USED PRIOR TO REPLETION : HYPERCALCEMIA CAN WORSEN.
2. Biphosphonates • Most useful agents • Prevent osteoclastic bone resorption : inhibit prenylation of GTP, also are cytotoxic to osteoclasts. • BPN approved : Zoledronate , pamidronate • Comparative studies indicate : improved response rates for zoledronate • Dose : 4 mg , IV, over 5 min • 8mg : for refractory hypercalcemia • Effects appears in 3-4 days, peaks in 7-10 days , lasts for 2 weeks- 2 months • ADR: const. symps, fever, hypophosphatemia, hypomagnesemia
3. Calcitonin • Inhibits bone resorption, reduces renal reabsorption • Source : salmon calcitonin • Dose: 4 IU/kg, SC/IM, every 12 hrs • Tachyphylaxis develops rapidly • Efficacy limited to 24-48 hrs. 4. Steroids • Effective in MM and lymphomas : cytotoxic • Onset is slow, develops over weeks • MOA : suppression of tumor and reduced gut absorption of calcium.
4. RANKL antibody • Denosumab : monoclonal ab, interferes with RANKL binding 5. Decoy RANKl ligand , osteoprotegerin No RCTS for above agents. 6. RRT : considered for severe and refractory hypercalcemia.
Prognosis • Development in lung ca : suggestive of unresectability, poor prognosis • 20 % MM presents with hypercalcemia : represents adv ds. , poor prognosis • Those with other solid tumors : grim survival, median survival 30-60 days.
3. SVC Syndrome • Pathophysiology
Etiology • Malignant cause 1. Lung ca : small cell ca (m.c. ) – 34 % > squamous ca ( 21 %) > adenoca (14 % ) 2. Lymphoma : NHL ( 13 %) > HL ( 0.8 % ) 3. Others ( 6 %) • Non malignant cause • Blastomycosis • Histoplasmosis • TB • Nocardia • Syphilis • Idiopathic mediastinal fibrosis • Goitre • Thymoma • Sarcoidosis • Prior radiation • metastases
Signs and symptoms • Depends upon the acuity of obstruction : Acute: • no time for collateral formation • Venous hypertension cause symptoms : cough, dypnea, edema of H&N • Rarely : hoarseness, headaches, chest pain, dysphagia Signs • Plethora, edema of H& N • JVP distension • Tachycardia • Rarely, papilledema and stridor.
Diagnosis • Initial investigation : CXR, CECT • Venography or MRI : to better define extent of obstruction • Aim to achieve tissue diagnosis at the earliest : sputum cytology, BAL, thoracoscopy, FNAC, LN Bx, mediastinoscopy, VATS, Open thoracotomy.
Treatment Radiotherapy • In those with established diagnosis • 30 Gy in 10 fractions : m.c. • Curative intent : 50 Gy in 25 fractions Chemotherapy • In chemosensitive tumors : germ cell ca, small cell lung ca, lymphoma, etc. Endovascular stenting • For those who lack tissue diagnosis • For emergency palliation of symptoms • Responses are durable ( 90% symptom free vs . 12 % with RT ) Surgial resection • Reserved for benign disease • In those with tracheal obstruction with resistance to CT/RT.
PROGNOSIS • In small cell ca and lymphomas : not a predictor of negative outcome • In these patients , curative intent is adviced.
4.EPIDURAL CORD COMPRESSION • Compression of dural sac and contents by extradural mass ( primary or met ) • M.c. : vertebral body • Site : thx (70%) > lumbar (20%) > cx (10%) • Lymphomas cause cord compression and IV foramen invasion without clinical compression : normal films, normal nuclear studies
Etiology • Benign causes : stenosis, abscess , hematoma
Signs and symptoms • Cardinal sign : pain ( 95%)- worsens on coughing, straining ; radicular distribution • Weakness • Autonomic dysfunction • Sensory deficit • Urinary retention : late presentation • Duration between pain and paralysis : variable ; 24-48 hrs to years
Diagnosis MRI : primary modality • More sensitive for paraspinal ds. • Has helped in defining extent of RT. ( clincally assessed had plan changed in 53 % ). • Better delineation of level of involvement. CT : faster than MRI ( in claustrophobics ) • Superior for vertbral body anatomy • Useful prior to surgical intervention
Treatment Steroids • In emergent situations, awaiting MRI • Reduction in peritumoral edema • High dose dexa : 100 mg bolus,thn, 96mg/d, tapered over 2 weeks • Or, 10 mg IV, then , 4mg/QID, taper over 2 wk RT • In highly radiosensitive tumors : first line • With multiple levels of involvement • Paraplegia for > 48 hrs. • Age > 65 yrs : sx associated with morbidity in elderly • Dose : 30 Gy , 10 fractions over 2 weeks (m.c.) Surgery • RT vs. RT + Sx : pt. with combination were mobile ( 84% vs 57 %) and ambulatory for longer periods ( 122 days vs 13 days ) • Statistically sign outcome in combination of RT + Sx.
Prognosis • Those paraplegic at presentation: 10 -19 % recover ambulation after RT alone vs. 62 % in those having Sx decompression upfront. • Early intervention : vital • Those ambulatory on presentation : 80 % remain ambulatory.
5. LEUCOSTASIS • Hyperleucocytosis : defined as leucocytes > 1 lakh/µL • Theories :  Integrins  Inflammatory cytokines  Adhesion of leucocyted to vascular endothelium releasing mediators  Expression of CD56/NCAM on AML blasts : correlates with development of leucostasis
Etiology • Most common : AML ( 10 -20 %) • Probably due to : large size and more adhesiveness of AML blasts. • Risk factors for development :  Total WBC counts  % of blasts  Rate at which counts rise  Lichtmann and Rowe : demonstrated that “LEUCOCRIT” , was closely related to development of leucostasis Leucocrit was proportional to number to circulating leucocytes and blasts.
Clinical manifestations • Obstruction of vascular beds • Tissue hypoxia cytokine release  thrombosis  organ dysfunction • Important capillary beds : CNS, RS, Renal, Coronaries involved by the rigid blasts. • Viscosity is seldom elevated : since RBCs are low due to marrow involvement
Treatment • Hydroxyurea : 20-30 mg/kg, requires 1-2 days to take effect. • RBC transfusions to be avoided until TLC < 50,000 to avoid ischemic events • leucopheresis : dose of 140 ml/kg ( 2 bld vol ) • Studies have failed to show significant benefit with leucopheresis • It is contraindicated in APML : risk of DIC, shock and death
Prognosis • No significant difference in complete response rates, disease free interval or survival rates in AML +/- leucostasis • Pulm. Leucostasis, hepatomegaly, hyperbilirubinemia, hypofibrinogenemia : predictors of poor outcome
6. Malignant cardiac tamponade • Pathophysiology • Fluid accumulation impairs LV expansion and diastolis filling. • SV reduces – tachycardia develops • Pressure equalizes in left & right heart ultimately • Tamponade develops when pericardium fails to expand : due to rapid fluid accumulation or thickening/ fibrosis.
Etiology • Pericardial involvement : 1 – 20 % • Lung, breast, lymphoma , leukemia • Pericardial effusions in cancer due to : Pericardial involvement ( 60 %) Idiopathic pericarditis (32 %) Radiation induced pericarditis (10 %) • Other causes : Dressler syndrome , RA, hypothyroidism.
Signs and symptoms Symptoms : • Dyspnea ( 85 %) • Cough ( 30%) • Orthopnea ( 25 %) • Chest pain ( 20 %) Signs : • JVP distension ( 100 %) • Tachycardia (100 %) • Pulsus paradoxus (89 %) • SBP < 90 mm Hg (52 %) • Preicardial rub (22 %) • ECG : low voltage complex, ST elevations, electrical alternans
Diagnosis 2D Echo : • Most useful, • Volume, fluidity & contents of effusion • Early : RV collapse, MR • Late : LA, RV collapse Cytologic examination : • essential for etiology (detection rates 50 – 100 %) • Cell count, cytology, cultures Pericardial Bx
Treatment • Tamponade : emergent drainage • Absolute indications :  PP < 20mmHg  Paradoxic pulse > 50 % of pulse pressure  Peripheral venous pressure > 13 mm Hg • ABC : as appropriate • Inotropes may be ineffective :  already a state of adrenergic overload  if mech ventilated , positive intrathoracic pressure • Observation adviced in ( tamponade seen in 20 %):  Asymptomatic  Minimal effusion , < 1 cm
Other therapy • RT In hematopoetic ca, 67 % control Non invasive Risk of radiation induced pericarditis • CT  chemo sensitive tumors : lymphoma , ca breast Prevents recurrence in 73 % • Sclerotherapy, pericardial window, subxiphoid pericardiotomy
7. Chemo induced cardiotoxicity ESMO guidelines, 2010
CLASSIFICATION • Type I : more serious, permanent myocardial damage e.g. doxorubicine • Type II : reversible usually e.g. trastuzumab • Acute onset : rare form . may occur immediately after a single dose or a course of anthracycline therapy, with clinical manifestations occurring within a week of treatment. • These may be in the form of transient electrophysiological abnormalities, Sinus tachycardia is the most common • Subacute : within days or weeks after completion of chemotherapy , results in acute failure of the left ventricle, pericarditis or a fatal pericarditis-myocarditis syndrome in some rare cases. • Chronic ( early onset, progressive ) : common and clinically important, presents within a year of treatment. It may persist or progress even after discontinuation of anthracyclines therapy, and may evolve into a chronic dilated cardiomyopathy in adult • Late chronic : causes ventricular dysfunction , heart failure and arrhythmia years to decades after chemotherapy has bee completed. Douraid K. Shakira, Kakil I Rasulb : J Clin Med Res 2009;1(1):8-12
RISK FACTORS • cumulative dose ( Cumulative doses of doxorubicin as low as 228 mg/m2 have shown to increase after-load or decrease contractility), • intravenous high single dose, • time of drug infusion <30 min, • history of prior irradiation, • use of other concomitant agents such as cyclophosphamide, trastuzumab, paclitaxel • female gender, • Extremes of age, • Underlying cardiovascular disease, • increase in time elapsed since therapy administration.
PATHOPHYSIOLOGY • multi-factorial. 1. Free radical–mediated myocyte damage : most thoroughly studied mechanisms in anthracyclines • The myocardium is more susceptible to free radical damage than other tissues because it has comparatively  less superoxide dismutase and catalase activity,  and its major defense, glutathione peroxidase, is suppressed by doxorubicin. • free radicals accumulate and cause severe lipid peroxidation, leading to extensive destruction . 2. Circulating pro-inflammatory cytokines : Doxorubicin induces the release of histamine and TNF-α from macrophages and interleukin-2 from monocytes • These cytokines have functional receptors on the myocardium and their release may result in dilated cardiomyopathy. 3. Adrenergic dysfunction and down regulation of myocardial histamine and β-adrenergic receptors has also been proposed as a cause for an evolving and established anthracycline–induced ventricular dysfunction
Signs and symptoms ACUTE PHASE • Transient ECG changes: prolonged QTc, ST elevations, T flattening, Sinus tachy • Pericarditis • Myocarditis • Serious arrhythmias ( 0.7 %): SVT, VT , junctional tachy CHRONIC • Chronic dilated cardiomyopathy • Restrictive cardiomyopathy • Heart failure • Arrythmias • Severe LV dysfunction • Sudden death
• Periodic monitoring : 2 DEcho is suggested especially for anthracyclines and their derivates, or monoclonal antibodies. • Baseline clinical and ECG evaluation are recommended in all patients undergoing anthracycline therapy [III, A]. • Assessment of baseline systolic and diastolic cardiac function with DEcho should be conducted before treatment with monoclonal antibodies [III, A] or anthracyclines and their derivates in patients aged >60 years, or with cardiovascular risk factors • Further evaluations of LVEF are recommended, even in asymptomatic patients, according to the follow timing:  after administration of half the planned dose of anthracycline, or  after administration of cumulative dose of doxorubicin 300 mg/m2, epirubicin 450 mg/m2 or mitoxantrone 60 mg/m2 [III, A] or  after administration of a cumulative dose of doxorubicin of 240 mg/m2 or epirubicin 360 mg/m2 in patients aging <15 years or >60 years [III, B];  before every next administration of anthracycline [III, A];  after 3, 6 and 12 months from the end of therapy with anthracycline [III, B]. MANAGEMENT & TREATMENT GUIDELINES ( ESMO , 2010 )
• During the echocardiographic assessments, patterns of PW Doppler of LV inflow tract and TDI-PW Doppler of mitral anulus should also be evaluated to detect initial signs of LV dysfunction that might occur before reduction of LVEF. • Periodic monitoring (every 12 weeks) of cardiac function is also suggested for those patients receiving monoclonal antibodies, especially if previously treated with anthracycline [III, A]. • Assessment of cardiac function is recommended 4 and 10 years after anthracycline therapy in patients who were treated at <15 years of age [III, B], or even at age >15 years but with cumulative dose of doxorubicin of >240 mg/m2 or epirubicin >360 mg/m2 [III, B].
• LVEF reduction of ‡20% from baseline despite normal function or LVEF decline <50% necessitate reassessment or discontinuation of therapy and further frequent clinical and echocardiographic checks. • Aggressive medical treatment of those patients, even asymptomatic, who show LV dysfunction at 2DEcho after anthracycline therapy is mandatory, especially if the neoplasia could have a long-term survival : ACE inhibitors and b-blockers and the earlier HF therapy is begun (within 2 months from the end of anthracycline therapy), the better the therapeutic response • role for biomarkers of cardiotoxicity is not well defined enough to include them as routine screening measurements. • a useful approach, even if rather costly and still controversial, is performing baseline assessment of biomarker concentrations and periodic measurements during therapy (at the end of chemotherapy administration, after 12, 24, 36, 72 h and 1 month later for troponin I; at the end of medicament infusion and after 72 h for BNP) to identify patients who need further cardiac assessment [III, C].
THANK YOU !!

More Related Content

Onco emergencies : DR. DEVAWRAT BUCHE

  • 2. CANCER BURDEN GLOBAL BURDEN • In 2000, burden of new case estimated 10.1 million • 56 % of cancer deaths in developing countries • Lung cancer >> stomach ca > prostate, colorectal ca • Develpoed countries : breast >> colorectal > lung > uterus • Males : lung > stomach> liver > H&N • Females : breast, cervix > stomach> lung > colorectal BURDEN IN INDIA • 2 – 2.5 million cases at a given time • Year 2000 : 8 lakh new cases, 5.5 lakh deaths • Heavy tobacco use : leading cause • 70 % present at advanced stages ( T3 – T4 stages ) : heavy mortality. ( MOHFW and TMH EBM data )
  • 3. • Any cancer may present itself as an emergency due to :  mass effect ( SVC syndrome, cord compression, leucostasis , gut obstruction etc.) Tumor invasion ( sentinal/ torrential bleed, effusions and tamponade ) Paraneoplastic syndrome ( hypercalcemia, SIADH, etc. ) Chemo induced damage ( heart failure, pancreatitis, severe infections, renal and hepatic failure , etc. )
  • 4. Considerations before intervention • Is the condition truly emergent ? • malignancy or a benign process ? • Specific tumor type ? • Tumor stage ? • Studies required to establish diagnosis ? • Prognosis and impact of intervention on patient ? • WHAT ARE THE WISHES OF THE PATIENT AND FAMILY ??? Irvin & Rippe, 7th edition
  • 5. ONCOLOGICAL EMERGENCIES • Tumor lysis syndrome • Malignant hypercalcemia • SVC syndrome • Epidural cord compression • Leucostasis • Malignant pericardial effusion/ tamponade • Chemo induced cardiotoxicity • Others : SIADH /hyponatremia, bleeding, febrile neutropenia, DIC , etc.
  • 6. 1. TUMOR LYSIS SYNDROME • Syndrome of metabolic derangements • Observed in cancers with large tumor burden, high proliferative rates or high chemosensitivity. • Metabolic derangement due to massive cell lysis and outpouring of intracellular chemicals: Hyperuricemia Hyperkalemia Hyperphosphatemia Hypocalcemia uremia
  • 7. Incidence • most frequently in patients with NHL and other hematologic malignancies,particularly Burkitt’s lymphoma, ALL, and acute myeloid leukemia (AML). • The overall incidence of LTLS and CTLS ranges from • 14%-17% and 3%-5% in AML, • 21%-30% and 5%-8% in ALL, • and 19%-40% and 6%-20% in NHL • solid tumors : occurrences are rare, with a very high mortality ( 1 in 3 )
  • 9. Classification • currently no universally accepted system for classification and grading. • The most recent and preferred is : Cairo and Bishop classification system • based on defining laboratory or clinical TLS (LTLS or CTLS). • This system distinguishes between patients who do not require therapeutic intervention versus those experiencing life-threatening clinical abnormalities. • LTLS is considered to be either present or absent, • whereas the grade of CTLS is defined by the maximal grade of the clinical manifestation
  • 12. Clinical manifestations • may occur before the start of chemotherapy • observed more commonly within 12 to 72 hours after the initiation of cytoreductive therapy • nausea, vomiting, diarrhea, • anorexia, • Lethargy, • edema, fluid overload, congestive heart failure, • hematuria, • cardiac dysrhythmias, • seizures, • muscle cramps, tetany, • syncope, and possible sudden death. • Complications can compromise the efficacy or further administration of chemotherapy.
  • 14. Prevention HIGH RISK PATIENTS • Adequate hydration and urine output are of high importance in preventing TLS • should be admitted to an intensive care unit • rasburicase should be used in the initial management of pediatric patients • Delaying tumor therapy • RRT as required
  • 15. INTERMEDIATE RISK PATIENTS • hydration, • allopurinol may be used • single dose of rasburicase might also be considered in pediatric patients LOW RISK PATIENTS • watch-and-wait approach
  • 17. FLUIDS AND HYDRATION • Aggressive hydration and diuresis are fundamental to the prevention and management • Promotes the excretion of uric acid and phosphate by improving intravascular volume, RBF, and GFR. • Vigorous hydration is recommended for all patients in the intermediate to- high risk groups • Fluid intake should be maintained at approx 1-2 times maintenance, with a urine output of 80 to 100 mL/m2/h ALKALINIZATION • currently not recommended • risk of precipitation of calcium phosphate crystals • only indicated for patients with metabolic acidosis, in which case sodium bicarbonate may be considered based on the standards of the institution.
  • 18. ALLOPURINOL • competitive inhibitor of xanthine oxidase • Use of allopurinol has been shown to decrease the formation of uric acid and to reduce the incidence of obstructive uropathy DOSE • ORAL : 50 to 100 mg/m2 every 8 hours (maximum dose, 300 mg/m2/d) or 10 mg/kg/d divided every 8 hours (maximum dose, 800 mg/d). • IV : 200 to 400 mg/m2/d in one to three divided doses (maximum dose, 600 mg/d). TIMING • initiated in intermediate risk patients no more than 12 to 24 hours before the start of induction chemotherapy UPTO 3-7 DAYS AFTER CT. • be continued until uric acid levels are normalized, and tumor burden, WBC count, and other laboratory values have returned to low-TLS risk levels
  • 19. • only prevents the formation of uric acid and does not reduce uric acid produced before the initiation of treatment.  patients with pre-existing severe hyperuricemia (> 7.5 mg/dL), treatment with rasburicase is preferred • Allopurinol can also cause an increase in serum levels and crystal deposition of the purine precursors xanthine and hypoxanthine, which can result in acute obstructive uropathy. • In addition, because allopurinol also reduces the degradation of other purines, particularly 6- mercaptopurine, dose reductions of 50% to 70% of 6-mercaptopurine and/or azathioprine are recommended. • Because allopurinol is excreted by the kidneys, a dose reduction of 50% is recommended in patients with renal insufficiency.
  • 20. RASBURICASE • Urate oxidase converts uric acid into allantoin, which is five to 10 times more soluble in urine than uric acid • recommended for the treatment of patients with hyperuricemia associated with LTLS or CTLS, or in the initial management of patients considered to be at high risk DOSE • 0.15 to 0.2 mg/kg once daily , as an IV infusion over 30 minutes for 5 days. • However, rasburicase has demonstrated activity even at lower doses and for shorter duration. • Therefore, a dose of 0.10 to 0.2 mg/kg daily, dependent on whether the intention is prevention or treatment may be used TIMING AND DURATION • 1 to 7 days • uric acid levels be monitored regularly
  • 21. ADR • rare , include anaphylaxis, rash, hemolysis, methemoglobulinemia, fever, neutropenia (with or without fever), respiratory distress, sepsis, and mucositis. • contraindicated in patients with a known G6PD deficiency and in pregnant or lactating females. • rasburicase will cause the degradation of uric acid within blood samples : assay, which is preferably done within 4 hours of collection.
  • 22. B.HYPERPHOSPHATEMIA Initial treatment: • eliminating phosphate from IV solutions, • maintaining adequate hydration, • administration of phosphate binders. • Aluminum hydroxide 50 to 150 mg/kg/d is administered in divided doses orally or nasogastrically every 6 hours. • Its use should be limited to 1 to 2 days to avoid cumulative aluminum toxicity • other phosphate binders : such as calcium carbonate, sevelamer hydroxide, and lanthanum carbonate For severe hyperphosphatemia, • RRT : hemodialysis, peritoneal dialysis, or continuous venovenous hemofiltration has been used • Phosphate clearance was found to be better with hemodialysis as compared with continuous venovenous hemofiltration or peritoneal dialysis.
  • 24. MONITORING DURING TREATMENT • Check laboratory and clinical TLS parameters 4 to 6 hours after the initial administration of chemotherapy. • The TLS parameter consists of :  uric acid,  phosphate,  potassium,  creatinine,  calcium, and  LDH,  fluid input and urine output • Uric acid levels should be re-evaluated 4 hours after administration of rasburicase and every 6 to 8 hours thereafter until resolution of TLS • If TLS has not occurred after 2 days, the likelihood is essentially zero that the patient will experience TLS • Approx 3% require RRT. • Nephro consultation be obtained immediately if :  oliguria or anuria,  if there is persistent or elevated urea (> 150mg/dl), phosphate(>10mg/dl) or potassium levels(>7mmol/L), or life threatening hypocalcemia  in spite of optimal conservative measures
  • 25. Prognosis • Outcome variable • Solid tumors : high fatality ( upto 36 %)
  • 26. 2.MALIGNANT HYPERCALCEMIA • MOST COMMON • 10-20 % of patients PHYSIOLOGY
  • 27. • MECHANISMS IN MALIGNANCY : 1. Direct osteolysis by tumor 2. Increased osteoclastic resorption 3. Renal insufficiency PTHrP : Plays a role , elevated in 80 % patients. • Acitivity similar to PTH. • Stimulates osteoblasts  production of RANKL  osteoclasts activation  osteolysis & production of bone derived growth factors ( TGF β, IGF-1)  TUMOR CELL PROLIFERATION AND MORE PRODUCTION OF PTHrP  renal resorption increases in DCT • In some lymphomas, there is raised levels of Vit D metabolites increased gut absorption
  • 28. Etiology HISTOLOGY % Breast 19-30 Lung 10-35 Multiple myeloma 20-30 H& N 5-24 Renal 17
  • 29. Clinical presentation • Rapidity determines the severity • Constitutional : nausea, fatigue, lethargy, mental status changes • Reduced extravascular volume : malaise, fatigue, anorexia, polyuria • Decreased NM excitability : reduced NM tone, hyporeflexia • Pyschiatric symptoms :confusion, lethargy, coma • ECG: short QTc, wide QRS, prolonged PR, bradyarr., BBB, CHB
  • 30. Diagnosis Elevated serum calcium 1. Raised ionized calcium 2. Raised corrected sr. calcium = 0.8 (4 – alb)+ Ca Other lab studies to be done are : PTH levels, BUN, creatinine, phosphate, magnesium, Vit D levels.
  • 31. Differential diagnoses • Hyperparathyroidism • Milk alkali syndrome • Vit D, Vit A excess • Lithium • Thiazides • TPN
  • 32. Treatment CALCIUM LEVEL SYMPTOMS THERAPY < 12 mg/dl none Observation, or hydration followed by observation <12 mg/dl present Hydration, BPN 12 – 14 mg/dl present Hydration, BPN > 14 mg/dl present Hydration, BPN >14 mg/dl severe Hydration,loop diuretics, calcitonin, BPN Alternatives : plicamycin, gallium, prednisone, RRT
  • 33. • Decision to treat depends upon : Patient history Current disease QOL Patient and family wishes 1. HYDRATION • INITIAL THERAPY OF CHOICE • May require upto 3-7 litres/ 24 hrs • Loop diuretics to be used ONLY if CHF is a concern • IF DIURETICS USED PRIOR TO REPLETION : HYPERCALCEMIA CAN WORSEN.
  • 34. 2. Biphosphonates • Most useful agents • Prevent osteoclastic bone resorption : inhibit prenylation of GTP, also are cytotoxic to osteoclasts. • BPN approved : Zoledronate , pamidronate • Comparative studies indicate : improved response rates for zoledronate • Dose : 4 mg , IV, over 5 min • 8mg : for refractory hypercalcemia • Effects appears in 3-4 days, peaks in 7-10 days , lasts for 2 weeks- 2 months • ADR: const. symps, fever, hypophosphatemia, hypomagnesemia
  • 35. 3. Calcitonin • Inhibits bone resorption, reduces renal reabsorption • Source : salmon calcitonin • Dose: 4 IU/kg, SC/IM, every 12 hrs • Tachyphylaxis develops rapidly • Efficacy limited to 24-48 hrs. 4. Steroids • Effective in MM and lymphomas : cytotoxic • Onset is slow, develops over weeks • MOA : suppression of tumor and reduced gut absorption of calcium.
  • 36. 4. RANKL antibody • Denosumab : monoclonal ab, interferes with RANKL binding 5. Decoy RANKl ligand , osteoprotegerin No RCTS for above agents. 6. RRT : considered for severe and refractory hypercalcemia.
  • 37. Prognosis • Development in lung ca : suggestive of unresectability, poor prognosis • 20 % MM presents with hypercalcemia : represents adv ds. , poor prognosis • Those with other solid tumors : grim survival, median survival 30-60 days.
  • 38. 3. SVC Syndrome • Pathophysiology
  • 39. Etiology • Malignant cause 1. Lung ca : small cell ca (m.c. ) – 34 % > squamous ca ( 21 %) > adenoca (14 % ) 2. Lymphoma : NHL ( 13 %) > HL ( 0.8 % ) 3. Others ( 6 %) • Non malignant cause • Blastomycosis • Histoplasmosis • TB • Nocardia • Syphilis • Idiopathic mediastinal fibrosis • Goitre • Thymoma • Sarcoidosis • Prior radiation • metastases
  • 40. Signs and symptoms • Depends upon the acuity of obstruction : Acute: • no time for collateral formation • Venous hypertension cause symptoms : cough, dypnea, edema of H&N • Rarely : hoarseness, headaches, chest pain, dysphagia Signs • Plethora, edema of H& N • JVP distension • Tachycardia • Rarely, papilledema and stridor.
  • 41. Diagnosis • Initial investigation : CXR, CECT • Venography or MRI : to better define extent of obstruction • Aim to achieve tissue diagnosis at the earliest : sputum cytology, BAL, thoracoscopy, FNAC, LN Bx, mediastinoscopy, VATS, Open thoracotomy.
  • 42. Treatment Radiotherapy • In those with established diagnosis • 30 Gy in 10 fractions : m.c. • Curative intent : 50 Gy in 25 fractions Chemotherapy • In chemosensitive tumors : germ cell ca, small cell lung ca, lymphoma, etc. Endovascular stenting • For those who lack tissue diagnosis • For emergency palliation of symptoms • Responses are durable ( 90% symptom free vs . 12 % with RT ) Surgial resection • Reserved for benign disease • In those with tracheal obstruction with resistance to CT/RT.
  • 43. PROGNOSIS • In small cell ca and lymphomas : not a predictor of negative outcome • In these patients , curative intent is adviced.
  • 44. 4.EPIDURAL CORD COMPRESSION • Compression of dural sac and contents by extradural mass ( primary or met ) • M.c. : vertebral body • Site : thx (70%) > lumbar (20%) > cx (10%) • Lymphomas cause cord compression and IV foramen invasion without clinical compression : normal films, normal nuclear studies
  • 45. Etiology • Benign causes : stenosis, abscess , hematoma
  • 46. Signs and symptoms • Cardinal sign : pain ( 95%)- worsens on coughing, straining ; radicular distribution • Weakness • Autonomic dysfunction • Sensory deficit • Urinary retention : late presentation • Duration between pain and paralysis : variable ; 24-48 hrs to years
  • 47. Diagnosis MRI : primary modality • More sensitive for paraspinal ds. • Has helped in defining extent of RT. ( clincally assessed had plan changed in 53 % ). • Better delineation of level of involvement. CT : faster than MRI ( in claustrophobics ) • Superior for vertbral body anatomy • Useful prior to surgical intervention
  • 48. Treatment Steroids • In emergent situations, awaiting MRI • Reduction in peritumoral edema • High dose dexa : 100 mg bolus,thn, 96mg/d, tapered over 2 weeks • Or, 10 mg IV, then , 4mg/QID, taper over 2 wk RT • In highly radiosensitive tumors : first line • With multiple levels of involvement • Paraplegia for > 48 hrs. • Age > 65 yrs : sx associated with morbidity in elderly • Dose : 30 Gy , 10 fractions over 2 weeks (m.c.) Surgery • RT vs. RT + Sx : pt. with combination were mobile ( 84% vs 57 %) and ambulatory for longer periods ( 122 days vs 13 days ) • Statistically sign outcome in combination of RT + Sx.
  • 49. Prognosis • Those paraplegic at presentation: 10 -19 % recover ambulation after RT alone vs. 62 % in those having Sx decompression upfront. • Early intervention : vital • Those ambulatory on presentation : 80 % remain ambulatory.
  • 50. 5. LEUCOSTASIS • Hyperleucocytosis : defined as leucocytes > 1 lakh/µL • Theories :  Integrins  Inflammatory cytokines  Adhesion of leucocyted to vascular endothelium releasing mediators  Expression of CD56/NCAM on AML blasts : correlates with development of leucostasis
  • 51. Etiology • Most common : AML ( 10 -20 %) • Probably due to : large size and more adhesiveness of AML blasts. • Risk factors for development :  Total WBC counts  % of blasts  Rate at which counts rise  Lichtmann and Rowe : demonstrated that “LEUCOCRIT” , was closely related to development of leucostasis Leucocrit was proportional to number to circulating leucocytes and blasts.
  • 52. Clinical manifestations • Obstruction of vascular beds • Tissue hypoxia cytokine release  thrombosis  organ dysfunction • Important capillary beds : CNS, RS, Renal, Coronaries involved by the rigid blasts. • Viscosity is seldom elevated : since RBCs are low due to marrow involvement
  • 53. Treatment • Hydroxyurea : 20-30 mg/kg, requires 1-2 days to take effect. • RBC transfusions to be avoided until TLC < 50,000 to avoid ischemic events • leucopheresis : dose of 140 ml/kg ( 2 bld vol ) • Studies have failed to show significant benefit with leucopheresis • It is contraindicated in APML : risk of DIC, shock and death
  • 54. Prognosis • No significant difference in complete response rates, disease free interval or survival rates in AML +/- leucostasis • Pulm. Leucostasis, hepatomegaly, hyperbilirubinemia, hypofibrinogenemia : predictors of poor outcome
  • 55. 6. Malignant cardiac tamponade • Pathophysiology • Fluid accumulation impairs LV expansion and diastolis filling. • SV reduces – tachycardia develops • Pressure equalizes in left & right heart ultimately • Tamponade develops when pericardium fails to expand : due to rapid fluid accumulation or thickening/ fibrosis.
  • 56. Etiology • Pericardial involvement : 1 – 20 % • Lung, breast, lymphoma , leukemia • Pericardial effusions in cancer due to : Pericardial involvement ( 60 %) Idiopathic pericarditis (32 %) Radiation induced pericarditis (10 %) • Other causes : Dressler syndrome , RA, hypothyroidism.
  • 57. Signs and symptoms Symptoms : • Dyspnea ( 85 %) • Cough ( 30%) • Orthopnea ( 25 %) • Chest pain ( 20 %) Signs : • JVP distension ( 100 %) • Tachycardia (100 %) • Pulsus paradoxus (89 %) • SBP < 90 mm Hg (52 %) • Preicardial rub (22 %) • ECG : low voltage complex, ST elevations, electrical alternans
  • 58. Diagnosis 2D Echo : • Most useful, • Volume, fluidity & contents of effusion • Early : RV collapse, MR • Late : LA, RV collapse Cytologic examination : • essential for etiology (detection rates 50 – 100 %) • Cell count, cytology, cultures Pericardial Bx
  • 59. Treatment • Tamponade : emergent drainage • Absolute indications :  PP < 20mmHg  Paradoxic pulse > 50 % of pulse pressure  Peripheral venous pressure > 13 mm Hg • ABC : as appropriate • Inotropes may be ineffective :  already a state of adrenergic overload  if mech ventilated , positive intrathoracic pressure • Observation adviced in ( tamponade seen in 20 %):  Asymptomatic  Minimal effusion , < 1 cm
  • 60. Other therapy • RT In hematopoetic ca, 67 % control Non invasive Risk of radiation induced pericarditis • CT  chemo sensitive tumors : lymphoma , ca breast Prevents recurrence in 73 % • Sclerotherapy, pericardial window, subxiphoid pericardiotomy
  • 61. 7. Chemo induced cardiotoxicity ESMO guidelines, 2010
  • 62. CLASSIFICATION • Type I : more serious, permanent myocardial damage e.g. doxorubicine • Type II : reversible usually e.g. trastuzumab • Acute onset : rare form . may occur immediately after a single dose or a course of anthracycline therapy, with clinical manifestations occurring within a week of treatment. • These may be in the form of transient electrophysiological abnormalities, Sinus tachycardia is the most common • Subacute : within days or weeks after completion of chemotherapy , results in acute failure of the left ventricle, pericarditis or a fatal pericarditis-myocarditis syndrome in some rare cases. • Chronic ( early onset, progressive ) : common and clinically important, presents within a year of treatment. It may persist or progress even after discontinuation of anthracyclines therapy, and may evolve into a chronic dilated cardiomyopathy in adult • Late chronic : causes ventricular dysfunction , heart failure and arrhythmia years to decades after chemotherapy has bee completed. Douraid K. Shakira, Kakil I Rasulb : J Clin Med Res 2009;1(1):8-12
  • 63. RISK FACTORS • cumulative dose ( Cumulative doses of doxorubicin as low as 228 mg/m2 have shown to increase after-load or decrease contractility), • intravenous high single dose, • time of drug infusion <30 min, • history of prior irradiation, • use of other concomitant agents such as cyclophosphamide, trastuzumab, paclitaxel • female gender, • Extremes of age, • Underlying cardiovascular disease, • increase in time elapsed since therapy administration.
  • 64. PATHOPHYSIOLOGY • multi-factorial. 1. Free radical–mediated myocyte damage : most thoroughly studied mechanisms in anthracyclines • The myocardium is more susceptible to free radical damage than other tissues because it has comparatively  less superoxide dismutase and catalase activity,  and its major defense, glutathione peroxidase, is suppressed by doxorubicin. • free radicals accumulate and cause severe lipid peroxidation, leading to extensive destruction . 2. Circulating pro-inflammatory cytokines : Doxorubicin induces the release of histamine and TNF-α from macrophages and interleukin-2 from monocytes • These cytokines have functional receptors on the myocardium and their release may result in dilated cardiomyopathy. 3. Adrenergic dysfunction and down regulation of myocardial histamine and β-adrenergic receptors has also been proposed as a cause for an evolving and established anthracycline–induced ventricular dysfunction
  • 65. Signs and symptoms ACUTE PHASE • Transient ECG changes: prolonged QTc, ST elevations, T flattening, Sinus tachy • Pericarditis • Myocarditis • Serious arrhythmias ( 0.7 %): SVT, VT , junctional tachy CHRONIC • Chronic dilated cardiomyopathy • Restrictive cardiomyopathy • Heart failure • Arrythmias • Severe LV dysfunction • Sudden death
  • 66. • Periodic monitoring : 2 DEcho is suggested especially for anthracyclines and their derivates, or monoclonal antibodies. • Baseline clinical and ECG evaluation are recommended in all patients undergoing anthracycline therapy [III, A]. • Assessment of baseline systolic and diastolic cardiac function with DEcho should be conducted before treatment with monoclonal antibodies [III, A] or anthracyclines and their derivates in patients aged >60 years, or with cardiovascular risk factors • Further evaluations of LVEF are recommended, even in asymptomatic patients, according to the follow timing:  after administration of half the planned dose of anthracycline, or  after administration of cumulative dose of doxorubicin 300 mg/m2, epirubicin 450 mg/m2 or mitoxantrone 60 mg/m2 [III, A] or  after administration of a cumulative dose of doxorubicin of 240 mg/m2 or epirubicin 360 mg/m2 in patients aging <15 years or >60 years [III, B];  before every next administration of anthracycline [III, A];  after 3, 6 and 12 months from the end of therapy with anthracycline [III, B]. MANAGEMENT & TREATMENT GUIDELINES ( ESMO , 2010 )
  • 67. • During the echocardiographic assessments, patterns of PW Doppler of LV inflow tract and TDI-PW Doppler of mitral anulus should also be evaluated to detect initial signs of LV dysfunction that might occur before reduction of LVEF. • Periodic monitoring (every 12 weeks) of cardiac function is also suggested for those patients receiving monoclonal antibodies, especially if previously treated with anthracycline [III, A]. • Assessment of cardiac function is recommended 4 and 10 years after anthracycline therapy in patients who were treated at <15 years of age [III, B], or even at age >15 years but with cumulative dose of doxorubicin of >240 mg/m2 or epirubicin >360 mg/m2 [III, B].
  • 68. • LVEF reduction of ‡20% from baseline despite normal function or LVEF decline <50% necessitate reassessment or discontinuation of therapy and further frequent clinical and echocardiographic checks. • Aggressive medical treatment of those patients, even asymptomatic, who show LV dysfunction at 2DEcho after anthracycline therapy is mandatory, especially if the neoplasia could have a long-term survival : ACE inhibitors and b-blockers and the earlier HF therapy is begun (within 2 months from the end of anthracycline therapy), the better the therapeutic response • role for biomarkers of cardiotoxicity is not well defined enough to include them as routine screening measurements. • a useful approach, even if rather costly and still controversial, is performing baseline assessment of biomarker concentrations and periodic measurements during therapy (at the end of chemotherapy administration, after 12, 24, 36, 72 h and 1 month later for troponin I; at the end of medicament infusion and after 72 h for BNP) to identify patients who need further cardiac assessment [III, C].