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Oncologic emergencies Oncologic emergencies Presentation Transcript

  • Oncologic Emergencies Dr. Jonathan Klein Resident, Radiation Oncology University of Toronto
  • Outline
    • Spinal Cord Compression
    • Brain Metastases
    • Superior Vena Cava Obstruction
    • Febrile Neutropenia
    • Hypercalcemia
    • Tumour Lysis Syndrome
  • Spinal Cord Compression Meyering SM. The Internet Journal of Nuclear Medicine. 5(1); 2008.
  • Spinal Cord Compression
    • Major emergency requiring radiation treatment
    • Can lead to permanent neurologic dysfunction
      • Ambulatory status is most important prognostic feature
        • 80-90% of patients ambulatory at treatment retain function
    • Usually compression from tumour
      • Can be 1 º or 2 º
      • Also hematoma, abscess, etc.
    1) Quint et al. JAMA. 2000 Feb 16;283(7):853-5.
  • Spinal Cord Compression
    • 2.5–5.0% of patients have spinal cord compression (SCC) within the last 2 years of illness.
    • Prostate, breast cancer, lung cancer most common
      • each ~15–20%
      • NHL, multiple myeloma, and renal cancer
        • ~5–10% of patients
        • Men 40-60 years with prostate cancer = 17% incidence
    • Thoracic spine affected in 60-80% of cases
    • 50% present with disease in multiple spinal areas
    1.Loblaw et al. Clin Oncol 2003; 15: 211–17 2. Schiff et al. Lancet Oncology. January 2005; 6(1):15-24.
  • Spinal Cord Compression - Prognosis
    • Poor prognosis
      • Median survival is ~3 months after SCC diagnosis
    • Histology impacts prognosis
      • Favourable
        • Breast, prostate, lymphoma, seminoma, myeloma
      • Unfavourable
        • Melanoma, lung, sarcoma, GI, renal, head & neck
    • Other factors
      • Presence of other bone/visceral metastases
      • Time from cancer diagnosis to cord compression
      • Time to developing motor deficits
    Loblaw. Curr Opin Supp Care. 2011. In progress
  • Signs/Symptoms
    • New onset back pain
      • Initially localized, typically increasing in intensity
      • In particular:
          • Pain that worsens when the patient is lying down
          • Pain with percussion of vertebral bodies
    • Weakness
      • 60-85% of patients present with weakness
      • ~2/3 are non-ambulatory at presentation
    • Late neurologic signs are associated with permanent deficits such as paraplegia
        • Urinary retention
        • Loss of sensory function
    1. Newton HB. Am Fam Physician 1999;59:878­8. 2. Quint DJ. JAMA 2000;283:853­5 3. Schiff et al. Lancet Oncology. January 2005:6(1);15-24.
  • Work-Up
    • Non-contrast MRI of whole spine is best test
      • If MRI not available, can use Myelography/CT
        • MRI is better because
          • Multiplanar imaging
          • No radiation
          • Contrast/needle not required to delineate lesions
          • Can detect multiple lesion
      • Should get whole spine MRI
        • 97.6% sensitivity; 100.0% specificity
        • Able to detect multi-level disease
    • Biopsy if:
      • metastatic disease not proven/documented
      • no previous diagnosis of cancer
    1) Quint DJ. JAMA 2000;283(7):853­5.
  • Treatment Rades D, Abrahm M. Nat Rev Clin Oncol. 2010;7(9).
  • Treatment
    • Corticosteroids
      • Sorensen et al, 1994
        • Single blind RCT of high dose (96mg) dexamethasone vs. no steroids
          • Ambulatory after treatment: 81% vs. 63%
          • Ambulatory 6 months later: 59% vs 33%
          • Life table analysis showed better ambulation course w/steroids (p<0.05).
    • Little agreement on dose
      • Vecht et al, 1989
        • No differences in pain, ambulation or bladder function between low and high dose steroids
          • High dose may be associated with increased toxicity
      • 1.Sorensen et al. European Journal of Cancer Volume 30, Issue 1 , 1994, Pages 22-27 
      • 2.Vecht et al. Neurology September 1989 39:1255.
  • Treatment
    • Sample prescription
      • 10mg dexamethasone IV bolus
      • 4 mg IV q6h
        • DO NOT delay while awaiting imaging results.
    • Caveat:
      • If lymphoma is suspected, consider withholding steroids until biopsy
        • May interfere with biopsy results
      • 1.Sorensen et al. Eur J Cancer. 1994; 30(1):22-27 
      • 2.Vecht et al. Neurology September 1989 39:1255.
  • However,…
    • Caveat to the Caveat:
        • Porter, 2008.
          • Retrospective study of 109 patients
          • Concluded that majority of diagnoses are NOT affected by steroids
            • Consider clinical picture and give steroids if needed
      • 1.Porter et al. Annals of Neurology. May 2008:63(5);662-7.
  • Treatment
    • Surgery/Radiotherapy
      • If patient has survival expectancy >3 months and single region compression
        • Debulking/stabilization surgery
        • Post-op radiotherapy
    • If patient has multiple levels or is not a surgical candidate
      • Radiotherapy alone
  • Patchell, 2005
    • Prospective trial
    • Surgery + 30Gy/10# RT
    • VS
    • 30Gy/10# RT alone
  • Patchell, 2005 Patchell et al. Lancet,  Volume 366, Issue 9486 , Pages 643 - 648, 20 August 2005.
  •  
  • Patchel, 2005
        • Surgery group also required less pain meds and steroids
    Surgery + RT RT alone Percent of patients able to walk after treatment (p=0.001) 84% 57% Time patients retained ambulation from treatment (p=0.003) 122 days 13 days Regained ambulation (pt’s unable to walk at treatment; p=0.01) 62% 19%
  • Patchell, 2005
      • Secondary endpoints:
      • 1) Median overall survival:
      • 126 days (Sx) vs 100 days (Sx+RT); p=0.033
      • 2) Maintenance of continence
      • 156 days (Sx) vs 17 days (Sx+RT); p=0.016
  • What to Prescribe?
    • Poor Prognosis
      • Unfavourable histology OR
      • Functional impairment/poor performance status
      • Maranzano, 2005
        • 15Gy/3# -4 day break- 15Gy/5# VS 8Gy/2# 1 week apart
          • No difference in OS, toxicity, pain, ambulation, bladder fxn
      • Maranzano, 2009
        • 16Gy/2# 1 week apart VS 8Gy/1#
          • No difference in OS, toxicity, pain, ambulation, bladder fxn
    1. Maranzano et al. J Clin Oncol 2005;23:3358-65. 2. Maranzano et al. Radiother Oncol 2009;93:174-9.
  • What to Prescribe?
    • Non-surgical and Good Prognosis
      • Rades (Score-1 study), 2009
        • 231 patients to long vs short course RT
          • Better 12 month progression free survival (72% vs 55%), 12 month local control (77% vs 61%)
          • No improvement in overall survival
      • Rades, 2004.
        • 214 patients to 30Gy/10# in 2 weeks vs 40Gy/20 in 4 weeks
          • Looked at functional outcomes
          • No difference in motor function, ambulation, other outcomes
    1. Rades et al. Int J Radiat Oncol Biol Phys 2009;73:228-34. 2. Rades et al. Cancer 2004;101:2687-92.
  • What to Prescribe?
    • Other studies
      • Sze et al, 2003.
        • Systematic review of 8Gy/1# vs multifraction RT
          • No difference between treatment protocols
      • Rades et al, 2005.
        • Retrospective study of 8Gy/1# vs 30Gy/10#
          • Found no difference in symptoms between schedules
      • Rades et al, 2009.
        • Prospective study of short course RT (1,5#) vs long course (10,15,20#)
          • Long course showed better 1yr local control (81% vs 61%).
          • No difference in overall survival or motor function
    1.Sze et al. Clin Oncol (R Coll Radiol) 2003; 15: 345–52. 2. Hanson and Roach. Handbook of Evidence-Based Radiation Oncology, 2010. p684
  • So? What’s the answer?
    • Depends on prognosis
      • Poor prognosis  8Gy/1#
        • Single fraction as effective as multi-fraction therapy
        • Much more convenient in patients with comorbidities
      • Good prognosis  Surgery + RT
        • If not receiving surgery, should enroll in clinical trial to assess optimal fractionation
        • 30Gy/10# most common prescription
    Loblaw Curr Opin Supp Care. 2011. In progress
  • Brain Metastases Vallow LA. Nat Rev Clin Onc. July 2009. 6;377-378
  • Brain Metastases
    • Most common form of malignant CNS involvement
      • Up to 200,000 cases/year in US
      • Most common sites:
        • Lung
        • Breast
        • Melanoma
        • Leukemia/lymphoma
      • Usually present in hemispheres due to higher blood flow
      • Causes symptoms via:
        • Direct compressive effects
        • Vasogenic edema
    1) Giglio et al. Curr Oncol Rep. 2010 Jan;12(1):50-9.
  • Clinical Presentation and Work Up
    • Signs/symptoms depend on location of mets
      • Common:
        • Headaches
        • Seizures
        • Focal deficits (e.g. weakness)
    • Work up includes
      • Physical Exam
        • delineate neurologic deficits
      • CT head
      • MR head
        • Can show lesions too small for CT
        • Better tissue contrast
    1) Giglio et al. Curr Oncol Rep. 2010 Jan;12(1):50-9.
  • Brain Metastases - Treatment 1) Giglio et al. Curr Oncol Rep. 2010 Jan;12(1):50-9.
    • Symptomatic treatment
      • Anticonvulsants
        • Non-enzyme inducing anticonvulsants are preferred
          • Pregabalin (Lyrica)
          • Levetiracetam
          • Lacosamide
        • Seizure prophylaxis is still performed, but no evidence
        • Hemorrhagic mets more likely cause seizures
          • Prophylaxis may be indicated in these cases
      • Dexamethasone
        • For vasogenic edema
          • If severe edema, midline shift or herniation
            • consider HIGH DOSE (12-24mg daily)
  • Brain Metastases – Prognostic Groups 1) Giglio et al. Curr Oncol Rep. 2010 Jan;12(1):50-9. 2) Gaspar et al. Int J Radiat Oncol Biol Phys 1997, 37:745.
    • Class I  Median survival 7.1 months
      • Age < 65
      • Karnofsky score > 70
      • No extracranial disease
      • Primary tumour not progressive
    • Class II  Median survival 4.2 months
      • Anyone NOT in Class I or Class III
    • Class III  Median survival 2.3 months
      • Karnofsky score < 70
  • Karnofsky Score
    • 100 – normal, no complaints, no signs of disease
    • 90 – capable of normal activity, few symptoms or signs of disease
    • 80 – normal activity with some difficulty, some symptoms or signs
    • 70 – caring for self, not capable of normal activity or work
      • i.e. independent for ADLs/IADLs
    • 60 – requiring some help, can take care of most personal requirements
    • 50 – requires help often, requires frequent medical care
    • 40 – disabled, requires special care and help
    • 30 – severely disabled, hospital admission indicated but no risk of death
    • 20 – very ill, urgent admission needed, supportive measures or treatment
    • 10 – moribund, rapidly progressive fatal disease processes
    • 0 – death.
    Karnofsky DA, Burchenal JH. (1949). &quot;The Clinical Evaluation of Chemotherapeutic Agents in Cancer.&quot; In: MacLeod CM (Ed),  Evaluation of Chemotherapeutic Agents.  Columbia Univ Press. Page 196.
  • Brain Metastases - Treatment 1) Giglio et al. Curr Oncol Rep. 2010 Jan;12(1):50-9.
    • Definitive Treatment  Surgery and RT
      • Limited role for chemo
    • Radiotherapy options
      • Whole Brain RT
        • Indicated in class I and II with single mets post-surgery
        • Palliative option in class III
      • Stereotactic Radiosurgery
  • Brain Metastases - Treatment 1) Patchell et al. N Engl J Med 1990; 322:494–500. 2) Patchell et al. JAMA 1998;280(17):1485-9
    • Stereotactic Radiosurgery
      • Oligometastases
        • Standard Treatment = Surgery + WBRT
          • Patchell, 1990 Surgery+WBRT vs biopsy+WBRT (48 patients)
            • Less locoregional recurrence (20% vs. 520%),
            • Better overall survival (40 vs. 15 weeks)
            • Longer maintenance of function (38 vs. 8 weeks)
          • Patchell, 1998 : Surgery vs Surgery+WBRT (95 patients)
            • Less locoregional recurrence
            • Less cause-specific mortality (14% vs. 44%)
            • No difference in overall survival or maintenance of function
  • Brain Metastases - Treatment 1) Limbrick et al. Surg Neurol. 2009 Mar;71(3):280-8 2) Mintz et al. Cancer. 1996; 78, 1470–1476.
    • Stereotactic Radiosurgery
      • No RCTs comparing SRS vs. surgery head-to-head
      • Oligometastases
        • Mintz, 1996.
          • Evaluated surgery + WBRT vs. WBRT alone
          • No difference in overall survival (5.6 months vs. 6.3 months)
        • Limbrick, 2009.
          • Evaluated WBRT with surgery/SRS; NOT head-to-head design
          • Overall median survival 20 months
          • Quoted comparable results for surgery+WBRT and SRS+WBRT
          • WBRT leads to faster onset of cognitive dysfunction
            • Therefore, SRS can be used as first-line RT for 1-2 mets
  • Brain Metastases - Treatment 1) Chougule et al. Int J Rad Onc Biol Phys. January 2000:48(3),supplement 1; 114.
    • Stereotactic Radiosurgery
      • Oligometastases
        • Chougule, 2000.
          • SRS vs SRS + WBRT vs WBRT alone
            • ~half of patients also received surgical intervention
          • No difference in overall survival between RT therapies
            • 2 º end-point: surgical resection provided survival benefit for patients who did not received SRS
          • Local control: 87%, 91%, 62%
            • Better in SRS arms
          • New metastasis appearance: 43%, 19%, 23%
            • Better in WBRT arms
  • Brain Metastases - Treatment
    • Aoyama et al. JAMA.  2006 Jun 7;295(21):2483-91
    • Chang et al. Lancet Oncology. 2009 Nov;10:1037-44.
    • Stereotactic Radiosurgery
      • Oligometastases
        • Aoyama, 2006.
          • SRS vs WBRT + SRS for patients with 1-4 mets (each <3cm)
          • Better 12 month local control (46.8% recurrence vs 76.4%)
          • Less salvage treatment required (10/65 vs 29/67)
          • No difference in overall survival or cause-specific mortality
        • Chang, 2009
          • Tested earning and memory function in SRS+WBRT vs SRS alone with 1-3 mets (54 patient)
          • Test stopped early due to unequivocal results
            • SRS+WBRT patient had more cognitive decline (52%)
            • SRS+WBRT had better locoregional control (73% vs 27%)
  • Brain Metastases - Treatment 1) Chargari et al. Nat Rev Clin Oncol. 2010 Nov;7(11):632-40. 2) Kondziolka et al. Int. J. Radiat. Oncol. Biol. Phys.1999:45;427–434. 3) Andrews et al. Lancet 2004:363;1665–1672.
    • Multiple Metastases
      • Not eligible for SRS and/or surgical intervention
        • Whole Brain Radiotherapy is standard
          • Provides short-term relief of neurologic symptoms in >70%
        • Kondziolka, 1999.
          • WBRT alone vs SRS + WBRT in 27 patients with 2-4 mets
            • Better locoregional control (6 vs 36 months)
            • No improvement in overall survival
        • Andrews, RTOG 9508, 2004
          • SRS + WBRT vs WBRT alone in 331 patients with 1-3 mets
            • Better locoregional control at 12 month followup (82% vs 71%)
            • Overall survival improved ONLY with 1 metastasis
            • No improvement in overall survival for 2-3 mets
  • Superior Vena Cava Obstruction http://www.lookfordiagnosis.com/mesh_info.php?term=Superior+Vena+Cava+Syndrome&lang=1
  • Superior Vena Cava Obstruction
    • Gradual compression of the superior vena cava, leading to edema and retrograde flow
    • 15,000 cases/year in US.
      • Associated with advanced disease
      • less than 10% survive >30 months after treatment.
    • Most commonly caused by intrathoracic malignancy
      • Usually lung cancer
        • Also mediastinal, metastatic and lymphoma
      • Before mid-20 th century, malignancy only accounted for 30-40% of SVCO
        • Infectious conditions (e.g. TB) caused majority
    º
    • Wudel et al. Superior vena cava syndrome. Curr Treat Options Oncol. 2001 Feb;2(1):77-91.
    • Rowell et al. Clin Oncol (R Coll Radiol). 2002 Oct;14(5):338-51.
  • Wudel et al. Superior vena cava syndrome. Curr Treat Options Oncol. 2001 Feb;2(1):77-91.
  • Clinical Presentation
    • Symptoms of superior vena cava syndrome
    • Symptom Patients, %
    • Facial swelling 71.9
    • Dyspnea 60
    • Cough 37.7
    • Arm swelling 27.6
    • Orthopnea 23.5
    • Pain 15.3
    • Dysphagia 10.6
    • Syncope 7.9
    • Headache 6.3
    • Stridor 4
    Wudel et al. Superior vena cava syndrome. Curr Treat Options Oncol. 2001 Feb;2(1):77-91.
  • Clinical Presentation
    • Physical signs of superior vena cava syndrome
    • Signs Patients, %
    • Dialated neck veins 70.1
    • Facial swelling 68.1
    • Prominent cutaneous veins 60.1
    • Arm swelling 41.3
    • Edema 30.5
    • Cyanosis 22.7
    • Vocal cord paralysis 4.7
    • Obtundation 1
    Wudel et al. Superior vena cava syndrome. Curr Treat Options Oncol. 2001 Feb;2(1):77-91.
  • Clinical Presentation
    • Average symptoms last ~45 days
      • 90% note duration of symptoms less than 8 weeks
    • Symptoms may improve spontaneously due to dilation of collateral circulation
    Higdon et al. Treatment of Oncologic Emergencies. American Family Physician. Volume 74, Number 11. December 1, 2006
  • Work Up
    • SVCO is usually diagnosed CLINICALLY
      • imaging (CT, plain XR, venography) can confirm
    • Biopsy should be obtained to evaluate for benign conditions and sensitive tumours
    1) Higdon et al. American Family Physician. Volume 74, Number 11. December 1, 2006 2) Wudel et al. Curr Treat Options Oncol. 2001 Feb;2(1):77-91.
  • Treatment
    • Immediate treatment can consist of
      • Supportive care including head and torso elevation
      • Steroids
      • Diuretics
    • Definitive management
      • Chemotherapy
      • Radiotherapy based on tumour type causing obstruction
        • Options: 30Gy/10#, 20Gy/5#, 37.5Gy/15#
      • Stent
    1.Rowell et al. Clinical Oncology. Volume 14, Issue 5. October 2002, Pages 338-351  2. Higdon et al. Treatment of Oncologic Emergencies. American Family Physician. Volume 74, Number 11. December 1, 2006
  • Treatment
    • ChemoRT
      • Most patients receive RT as first-line treatment
        • Little evidence for efficacy of RT over chemo
          • Chan, 1997  93% improvement with chemo, 94% improvement with RT
          • Pereira, 1999  No advantage to neoadjuvant chemo vs RT alone
          • Spiro, 1989  No advantage to RT over chemo
    1) Rowell et al. Clin Oncol (R Coll Radiol). 2002 Oct;14(5):338-51 2) Chan et al. Int J Radiat Oncol Biol Phys. 1997 Jun 1;38(3):513-20. 3) Pereira et al. Eur J Cancer 1999;34(suppl 4):1032 4) Spiro et al. Thorax 1983;38:501–50
  • Treatment
    • Stents
      • increasingly common
      • Seem to be safe and effective
        • No randomized trials yet of stenting vs. chemoRT
          • Wilson, 2008. (PMH)
            • Attempted to set up two head to head trials but failed
    • Rowell, 2002:
        • Systematic review
        • SVCO relief:
          • 95% stent vs 77% chemoRT
        • SVCO relapse:
          • 11% stent vs 17% chemoRT
    1) Spiro et al. Thorax 1983;38:501–50 2) Wilson et al. J Thorac Oncol. 2007 Jun;2(6):514-9. 3) Rowell et al. Clin Oncol (R Coll Radiol). 2002 Oct;14(5):338-51.
  • Febrile Neutropenia
  • Febrile Neutropenia
    • Definition:
      • Fever:
        • Oral temperature ≥ 38.3 without signs of noninfectious causes of increased temperature
        • OR
        • temperature of ≥ 38.0 C twice, lasting for at least 1 h or measured twice within 12 h
      • Neutropenia
        • Neutrophil count <500/mm 3
        • OR
        • Neutrophil count <1000/mm 3 with predicted decline to 500/ml within the next 2 days
    Link et al. Ann Hematol (2003) 82 (Suppl 2):S105–S117.
  • Febrile Neutropenia
    • Can be bacterial or fungal
    • Common condition
      • At least 20% of patients with neutrophil counts < 100 mm 3 have bacteremia
      • contributes to 50% of deaths associated with leukemia and lymphomas.
    Hughes et al. Clinical Infectious Diseases. 2002;34:730-51 Viscoli C. J Antimi­crob Chemother 1998;41(suppl D):S65­80.
  • Febrile Neutropenia
    • Investigations
      • cultures
      • CBC
      • BUN/Cr
      • transaminase measurements
    • If respiratory symptoms are present  CXR
      • may be clear due to lack of inflammatory response
    • Can consider outpatient treatment of low risk patients >16 years old
    Hughes et al. Clinical Infectious Diseases. 2002;34:730-51
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51. Febrile Neutropenia
    • Assess risk level
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51. Febrile Neutropenia
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51. Febrile Neutropenia
    • Initial treatment algorithm
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51. Febrile Neutropenia
    • Continuing treatment algorithm
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51.
    • Continuing treatment algorithm
    Febrile Neutropenia
  • Hughes et al. Clinical Infectious Diseases. 2002;34:730-51.
    • Continuing treatment algorithm
    Febrile Neutropenia
  • Hypercalcemia
  • Hypercalcemia
    • Presents in 20-30% of cancer patients
      • Usually presents late, so poor prognosis
        • Median survival of a few months
    • Mechanisms:
    • ● bone-resorbing cytokines
    • ● parathyroid hormone-related peptide
    • ● tumor-mediated calcitriol production
    • ● ectopic parathyroid hormone secretion.
    1) Lumachi et al. Curr Med Chem. 2008;15(4):415-21.
  • Sources of Hypercalcemia Lumachi et al. Curr Med Chem. 2008;15(4):415-21.
  • Hypercalcemia
    • Symptoms
      • Bones
      • Stones
      • Grones
      • Moans
    • Bad prognosis
      • Over 50 percent of patients die within 30 days of diagnosis of hypercalcemia
    Stewart AF. N Engl J Med 2005;352:373­9
  • Clinical Presentation
    • Bones = MSK
        • weakness, myopathy, bone pain
    • Stones = renal/GU
        • nephrolithiasis, renal insufficency, polyuria
    • Groans = GI
        • constipation, anorexia, N/V
    • Moans = CNS
      • hypertonia, confusion, obtundation, psychosis, ataxia, depression, coma
    Lumachi et al. Curr Med Chem. 2008;15(4):415-21.
  • Management of Hypercalcemia
    • Hydration with normal saline
    • Once hydrated:
      • IV bisphosphonate (30-90mg pamidronate most commonly used)
        • Pamidronate superior to most other bisphosphonates
          • Fatemi, 1992.
          • Vinholes, 1997.
        • Pamidronate 60-90mg tolerated and effective in majority (60-100%).
          • Nussbaum, 1993
        • 4mg zolendronate has been shown to be superior to pamidronate
          • Major, 2001.
    • Bisphosphonates are superior to hydration alone
      • Ralston, 2004.
    1) Lumachi et al. Curr Med Chem. 2008;15(4):415-21. 2) Fatemi et al. Calcif. Tissue Int., 1992, 50, 1073) 3) 3)Vinholes et al. J. Clin. Oncol., 1997, 15, 131. 4) Major et al. J. Clin. Oncol., 2001, 19, 558. 5) Nussbaum et al. Am J Med. 1993 Sep;95(3):297-304. 6) Ralston et al. Calcif. Tissue Int., 2004, 74, 1.
  • Management of Hypercalcemia
    • Other considerations
      • Loop diuretic
        • Only after volume status resolved
      • Steroids
        • May be effective with lymphoma and multiple myeloma due to direct anti-neoplastic activity
      • Calcitonin
      • Mithracin
      • Dialysis if necessary
    1) Stewart AF. N Engl J Med 2005;352:373­9 2) Lumachi et al. Curr Med Chem. 2008;15(4):415-21.
  • Tumour Lysis Syndrome
  • Tumour Lysis Syndrome
    • Clinical presentation - variable
      • GI: nausea, vomiting
      • Fluid imbalances: overload, edema, low urine
      • Cardiac: CHF, arrhythmias
      • MSK: lethargy, cramps, tetany
      • Neuro: syncope, seizures, and sudden death.  
      • GU: hematuria, flank or back pain
    Cairo et al. Tumour lysis syndrome: new therapeutic strategies and classification. British Journal of Haematology Volume 127, Issue 1. Pages 3–11, October 2004
  • Tumour Lysis Syndrome
    • Acute cell lysis
      • may be caused by chemotherapy and radiation therapy.
    • Release of intracellular products overwhelms the homeostasis
      • uric acid, phosphate, calcium, potassium
    • More common among hematologic malignancies
      • 3–7% incidence for acute leukemias 
      • 4–11% for lymphomas
    • Certain leukemia patients have incidences up to 25%
      • precursor B ALL, Burkitt’s lymphoma
    • Can also occur in large or chemosensitive tumors
      • Low incidence, unpredictable
    Mughal et al. Cancer Treatment Reviews (April 2010), 36 (2), pg. 164-176.
  • Tumour Lysis Syndrome - Definition
    • Cairo–Bishop definition of laboratory tumour lysis syndrome:
      • “ Either a 25% change or level above or below normal for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3 d before or 7 d after the initiation of chemotherapy.”
        • Usually occurs 1-5 days after start of therapy
    • Parameter Measurement
    • Uric acid 476 mmol/l OR 25% increase from baseline
    • Potassium 6.0 mmol/l OR 25% increase from baseline
    • Phosphorous 1.45 mmol/l OR 25% increase from baseline
    • Calcium 1.75 mmol/l OR 25% decrease from baseline
    Cairo et al. Tumour lysis syndrome: new therapeutic strategies and classification. British Journal of Haematology Volume 127, Issue 1. Pages 3–11, October 2004
  • Tumor Lysis Syndrome Definition
    • Cairo-Bishop definition of clinical tumour lysis syndrome:
      • Creatinine 1.5 x ULN
      • Cardiac arrhythmia
      • Seizure
    Cairo et al. British Journal of Haematology. October 2004:127(1); 3–11.
  • Tumour Lysis Syndrome - Risk
    • Risk Assessment
            • NHL ALL AML CLL (x10 3 WBC/ μ L) (x10 3 WBC/ μ L)
    • High Burkitt ≥ 100 ≥ 50
            • Lymphoblastic
            • B-ALL
    • Int DLBCL 50-100 10-50 10-100 Tx w/fludarabine
    • Low Indolent NHL ≤ 50 ≤ 10 ≤ 10
    Abu-Alfa et al. American Journal of Kidney Diseases (May 2010), 55 (5), Supplement 3, pg. S1-S13
  • Tumour Lysis Syndrome - Risk
    • Other patients with rapidly proliferating disease or expected rapid response to treatment are INTERMEDIATE risk.
    • All others are LOW risk
    Abu-Alfa et al. American Journal of Kidney Diseases (May 2010), 55 (5), Supplement 3, pg. S1-S13
  • Tumor Lysis Syndrome
    • Preventive measures are critical
      • Monitor electrolytes before and during treatment
      • Fluids to maintain urine output >100 cc/hr
        • Up to 3L/day/m 2 may be required
        • Supplementation with diuretics to keep output high
          • Controversial
          • Should only be considered if adequate volume status confirmed
          • Loop diuretics generally preferred
      • Allopurinol or rasburicase may be used for treatment/prevention
        • inhibits uric acid production and uropathy
    Hande et al. Am J Med. 1993 Feb;94(2):133-9.
  • Tumour Lysis Syndrome – Bottom Line Coiffier et al. J Clin Oncol  , v.26 , p.2767 , 2008 , Coiffier B. et al. 
  • The End…..Finally!