Oncological Emergencies Dr. Gary Harding MD, FRCPC Medical Oncology Fellow CancerCare Manitoba.

Oncological Oncological EmergenciesEmergencies

Dr. Gary Harding MD, FRCPCDr. Gary Harding MD, FRCPC

Medical Oncology Fellow Medical Oncology Fellow CancerCare ManitobaCancerCare Manitoba

CASE 1…CASE 1…

Mr. SVMr. SV

ID:ID: 65 year old male with PMHx of 65 year old male with PMHx of CAD and emphysemaCAD and emphysema

EC:EC: present to clinic with one week present to clinic with one week history of increasing SOBhistory of increasing SOB

HPI:HPI: 3 month history of weight loss, 3 month history of weight loss, decreased appetite, a change in his decreased appetite, a change in his chronic cough, and intermittent chronic cough, and intermittent hemoptysis hemoptysis

On Physical ExaminationOn Physical Examination

Inspection:Inspection:

Respiratory ExaminationRespiratory Examination StridorStridor

Dullness to percussion on right lower Dullness to percussion on right lower lung fieldslung fields

Increased tactile fremitus to right Increased tactile fremitus to right lower lung fieldslower lung fields

Decreased A/E to right lower lung Decreased A/E to right lower lung fieldsfields

Chest X-Ray…Chest X-Ray…

right pleural effusion

ThoracentesisThoracentesis ExudateExudate

Gram stain Gram stain – NegativeNegative

AFB stainAFB stain– NegativeNegative

CytologyCytology– non-small cell lung cancernon-small cell lung cancer

Large cell typeLarge cell type

T1-weighted axial MRI demonstrating T1-weighted axial MRI demonstrating paratracheal soft tissue mass that invades into paratracheal soft tissue mass that invades into the SVCthe SVC

Superior Vena Cava Superior Vena Cava SyndromeSyndrome

DefinitionDefinition

Obstruction of blood flow in the Obstruction of blood flow in the superior vena cava results in signs superior vena cava results in signs and symptoms of SVC syndromeand symptoms of SVC syndrome

EtiologyEtiology

Caused by either invasion or external Caused by either invasion or external compression of the SVC by compression of the SVC by contiguous pathologic processcontiguous pathologic process

Right lung pathology, lymph nodes, Right lung pathology, lymph nodes, other mediastinal structures, or other mediastinal structures, or thrombosisthrombosis

EtiologyEtiology

Before antibiotics the most common Before antibiotics the most common causes were from complications of causes were from complications of untreated infectionuntreated infection– Syphilitic thoracic aneurysmsSyphilitic thoracic aneurysms– fibrosing mediastinitisfibrosing mediastinitis

Malignancy is presently the most Malignancy is presently the most common causecommon cause

Symptoms and SignsSymptoms and Signs

As the obstruction develops venous As the obstruction develops venous collaterals are formedcollaterals are formed

Symptom onset depends on speed of Symptom onset depends on speed of SVC obstruction onsetSVC obstruction onset

Malignant disease can arise in weeks Malignant disease can arise in weeks to monthsto months– Not enough time to develop collateralsNot enough time to develop collaterals

Fibrosing mediastinitis can take Fibrosing mediastinitis can take years to have symptomsyears to have symptoms

Symptoms and SignsSymptoms and Signs

Central venous pressures remain Central venous pressures remain high even in collateralshigh even in collaterals– High pressures cause the characteristic High pressures cause the characteristic

clinical pictureclinical picture

Shortness of breath is the most Shortness of breath is the most common symptomcommon symptom11

1. Parish, JM, Marschke, RF Jr, Dines, DE, Lee, RE. Etiologic 1. Parish, JM, Marschke, RF Jr, Dines, DE, Lee, RE. Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc 1981; considerations in superior vena cava syndrome. Mayo Clin Proc 1981; 56:407. 56:407.

Signs and SymptomsSigns and Symptoms Facial swelling or head fullnessFacial swelling or head fullness

– exacerbated by bending forward or lying exacerbated by bending forward or lying downdown

CoughCough

Arm edemaArm edema

CyanosisCyanosis

Facial swelling associated with SVC Facial swelling associated with SVC Syndrome in a patient with malignancySyndrome in a patient with malignancy

Physical FindingsPhysical Findings

Venous distension Venous distension – neckneck– chest wallchest wall

Pemberton’s SignPemberton’s Sign

Facial EdemaFacial Edema

Patient who presented with progressively enlarging Patient who presented with progressively enlarging veins over the anterior chest wall. A diagnosis of a veins over the anterior chest wall. A diagnosis of a right-sided superior sulcus (Pancoast) tumor right-sided superior sulcus (Pancoast) tumor compressing the SVC was made.compressing the SVC was made.

Etiology: MalignancyEtiology: Malignancy

Lung cancer is the most commonLung cancer is the most common22

Lymphoma is second most commonLymphoma is second most common

together represent 94% of casestogether represent 94% of cases

2. Escalante, CP. Causes and management of superior vena 2. Escalante, CP. Causes and management of superior vena cava syndrome. Oncology (Huntingt) 1993; 7:61.cava syndrome. Oncology (Huntingt) 1993; 7:61.

NSCLCNSCLC

2-4% of bronchogenic cancer 2-4% of bronchogenic cancer patients develop SVC syndromepatients develop SVC syndrome33

extrinsic compression or direct extrinsic compression or direct invasioninvasion– primary tumor or by enlarging primary tumor or by enlarging

mediastinal nodesmediastinal nodes

3. Armstrong, BA, Perez, CA, Simpson, JR, Hederman, MA. 3. Armstrong, BA, Perez, CA, Simpson, JR, Hederman, MA. Role of irradiation in the management of superior vena cava Role of irradiation in the management of superior vena cava syndrome. Int J Radiat Oncol Biol Phys 1987; 13:531.syndrome. Int J Radiat Oncol Biol Phys 1987; 13:531.

Small Cell Lung CancerSmall Cell Lung Cancer

Greatest riskGreatest risk

20% will develop SVC obstruction20% will develop SVC obstruction33

more common because SCLC tends more common because SCLC tends to occur centrally in contrast to other to occur centrally in contrast to other typestypes

LymphomaLymphoma

2-4% of patients2-4% of patients

predominantly non-Hodgkin’s lymphomapredominantly non-Hodgkin’s lymphoma44

Hodgkin’s rarely causes SVC syndromeHodgkin’s rarely causes SVC syndrome

4. Perez-Soler, R, McLaughlin, P, Velasquez, WS, et al. Clinical 4. Perez-Soler, R, McLaughlin, P, Velasquez, WS, et al. Clinical features and results of management of superior vena cava features and results of management of superior vena cava syndrome secondary to lymphoma. J Clin Oncol 1984; 2:260.syndrome secondary to lymphoma. J Clin Oncol 1984; 2:260.

LymphomaLymphoma

Extrinsic compression caused by Extrinsic compression caused by enlarging lymph nodesenlarging lymph nodes

subtypes of large B cell can be subtypes of large B cell can be intravascular and cause occlusion intravascular and cause occlusion (angiotropic)(angiotropic)

diffuse large cell and lymphoblastic diffuse large cell and lymphoblastic are most commonly associated with are most commonly associated with SVC syndromeSVC syndrome

Other cancersOther cancers

ThymomaThymoma

primary mediastinal germ cell primary mediastinal germ cell neoplasmneoplasm

solid tumors with mediastinal solid tumors with mediastinal nodal metastasesnodal metastases– breast cancer most common typebreast cancer most common type

Other causesOther causes

Post radiation local vascular fibrosis Post radiation local vascular fibrosis can also be considered in oncology can also be considered in oncology patientspatients– Thoracic radiation treatment may Thoracic radiation treatment may

predate syndrome by many yearspredate syndrome by many years

Other causesOther causes

ThrombosisThrombosis Indwelling central venous cathetersIndwelling central venous catheters Subcutaneous tunneled catheters Subcutaneous tunneled catheters

have fewer thrombotic and infectious have fewer thrombotic and infectious complicationscomplications– Can also cause pulmonary embolismCan also cause pulmonary embolism55

5. Sivaram, CA, Craven, P, Chandrasekaran, K. Transesophageal 5. Sivaram, CA, Craven, P, Chandrasekaran, K. Transesophageal echocardiography during removal of central venous catheter echocardiography during removal of central venous catheter associated with thrombus in superior vena cava. Am J Card Imaging associated with thrombus in superior vena cava. Am J Card Imaging 1996; 10:266. 1996; 10:266.

DiagnosisDiagnosis

Timely identification of the cause is Timely identification of the cause is essentialessential

Radiographic studies are usefulRadiographic studies are useful Up to 60% of patients with SVC Up to 60% of patients with SVC

syndrome related to neoplasm do not syndrome related to neoplasm do not have a known diagnosis of cancerhave a known diagnosis of cancer66

– Need a tissue biopsy for histologic Need a tissue biopsy for histologic studiesstudies

6. Schraufnagel, DE, Hill, R, Leech, JA, Pare, JA. Superior vena caval 6. Schraufnagel, DE, Hill, R, Leech, JA, Pare, JA. Superior vena caval obstruction. Is it a medical emergency?. Am J Med 1981; 70:1169. obstruction. Is it a medical emergency?. Am J Med 1981; 70:1169.

Radiographic StudiesRadiographic Studies

Most patients have an abnormal Most patients have an abnormal chest x-ray at presentationchest x-ray at presentation

Most common findings areMost common findings are– Mediastinal wideningMediastinal widening– Pleural effusionPleural effusion

CT ChestCT Chest

Preferred choicePreferred choice

IV contrast IV contrast – defines the level of obstructiondefines the level of obstruction– Maps out collateral pathwaysMaps out collateral pathways– Can identify underlying cause of Can identify underlying cause of

obstructionobstruction

VenographyVenography

Bilateral upper arm venograpyBilateral upper arm venograpy– superior to CT to define site of superior to CT to define site of

obstructionobstruction– Does not define cause unless Does not define cause unless

thrombosis is solely responsiblethrombosis is solely responsible

Helical CTHelical CT

With bilateral upper arm IV contrast With bilateral upper arm IV contrast injectioninjection

Best visualization of level of Best visualization of level of obstruction and causeobstruction and cause

MRIMRI

Can be useful in patients with IV Can be useful in patients with IV contrast allergiescontrast allergies

T1-weighted axial MRI demonstrating the T1-weighted axial MRI demonstrating the primary tumor and the paratracheal soft primary tumor and the paratracheal soft tissue mass that invades into the SVCtissue mass that invades into the SVC

Same patient’s MRI with different Same patient’s MRI with different technique to further define the technique to further define the intramural massintramural mass

Histologic DiagnosisHistologic Diagnosis

EssentialEssential

Guides treatmentGuides treatment

Aids in defining prognosisAids in defining prognosis

Histologic DiagnosisHistologic Diagnosis Sputum cytology, pleural fluid Sputum cytology, pleural fluid

cytology, biopsy of enlarged cytology, biopsy of enlarged peripheral nodesperipheral nodes

Bone marrow biopsy for NHLBone marrow biopsy for NHL

Bronchoscopy, mediastinoscopy, or Bronchoscopy, mediastinoscopy, or thoracotomy are more invasive but thoracotomy are more invasive but sometimes necessarysometimes necessary

Treatment of Oncologic Treatment of Oncologic CausesCauses

TreatmentTreatment

Aimed at underlying causeAimed at underlying cause

Evolution of thought has occurred in Evolution of thought has occurred in recent yearsrecent years

Historically SVC syndrome was Historically SVC syndrome was considered a potentially life-considered a potentially life-threatening emergencythreatening emergency

Standard of care was immediate Standard of care was immediate radiotherapyradiotherapy– Zap nowZap now– Ask questions laterAsk questions later

The emergent approach is not The emergent approach is not appropriate for most patientsappropriate for most patients

Newer strategiesNewer strategies

Emergent to UrgentEmergent to Urgent

Symptomatic obstruction is usually a Symptomatic obstruction is usually a prolonged processprolonged process

Most patients are not in immediate Most patients are not in immediate danger at presentationdanger at presentation

Most have time for a full diagnostic Most have time for a full diagnostic work upwork up

Emergent to UrgentEmergent to Urgent

Prebiopsy radiation can obscure the Prebiopsy radiation can obscure the diagnosisdiagnosis

Current strategies aim at accurate Current strategies aim at accurate diagnosis of underlying etiology diagnosis of underlying etiology before therapybefore therapy

ExceptionException to new ruleto new rule

StridorStridor– Central airway obstruction or laryngeal Central airway obstruction or laryngeal

edemaedema True medical emergencyTrue medical emergency Immediate action neededImmediate action needed

– Possible intubation and ICU admissionPossible intubation and ICU admission– Immediate therapy to target obstruction Immediate therapy to target obstruction

neededneeded

PrognosisPrognosis……

Linked to tumor histology and Linked to tumor histology and stage at presentationstage at presentation

Treatment Sensitive TumorsTreatment Sensitive Tumors

NHLs, germ cells, and limited-stage NHLs, germ cells, and limited-stage small cell lung cancers usually small cell lung cancers usually respond to chemotherapy and or respond to chemotherapy and or radiationradiation

Can achieve long term remission with Can achieve long term remission with tumor specific directed therapytumor specific directed therapy

Symptomatic improvement usually Symptomatic improvement usually takes 1-2 weeks after start of takes 1-2 weeks after start of therapytherapy

Note: CorticosteroidsNote: Corticosteroids

Controversial issue with regards to Controversial issue with regards to treatment benefit at presentationtreatment benefit at presentation

Non-small cell lung cancerNon-small cell lung cancer

SVC obstruction is a strong predictor SVC obstruction is a strong predictor of poor prognosisof poor prognosis

Median survival around 5 monthsMedian survival around 5 months77

Choice of therapy considers Choice of therapy considers likelihood of response to each likelihood of response to each modalitymodality

7. Martins, SJ, Pereira, JR. Clinical factors and prognosis in non-7. Martins, SJ, Pereira, JR. Clinical factors and prognosis in non-small cell lung cancer. Am J Clin Oncol 1999; 22:453. small cell lung cancer. Am J Clin Oncol 1999; 22:453.

Non-small cell lung cancerNon-small cell lung cancer

Goal usually directed to palliation Goal usually directed to palliation rather than long term remissionrather than long term remission

Palliative radiation and Palliative radiation and chemotherapy can be usedchemotherapy can be used

Intraluminal StentsIntraluminal Stents Endovascular placement under Endovascular placement under

fluoroscopyfluoroscopy

Patients who have recurrent disease Patients who have recurrent disease in previously irradiated fieldsin previously irradiated fields

Tumors refractory chemotherapyTumors refractory chemotherapy

Patient too ill to tolerate radiation or Patient too ill to tolerate radiation or chemotherapychemotherapy

Intraluminal StentsIntraluminal Stents

Some data suggests benefit from Some data suggests benefit from immediate stent placement in NSCLC immediate stent placement in NSCLC at presentationat presentation88

Tends to provide more rapid relief of Tends to provide more rapid relief of symptomssymptoms

Issue of anticoagulation after is not Issue of anticoagulation after is not resolvedresolved

8. Rowell, NP, Gleeson, FV. Steroids, radiotherapy, 8. Rowell, NP, Gleeson, FV. Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review. Clin Oncol (R carcinoma of the bronchus: a systematic review. Clin Oncol (R Coll Radiol) 2002; 14:338. Coll Radiol) 2002; 14:338.

CASE 2…CASE 2…

Mr. ECMr. EC ID:ID: 56 year old man with history of 56 year old man with history of

HTN and osteoarthrtisHTN and osteoarthrtis EC:EC: presents to family doctor with presents to family doctor with

one month history of back pain that one month history of back pain that is not responding to Tylenolis not responding to Tylenol– Pain beginning to wake him at nightPain beginning to wake him at night– More pain with recumbancyMore pain with recumbancy– Some shooting pains down right legSome shooting pains down right leg

ROS:ROS: negative negative

On examinationOn examination vitals stable, no fevervitals stable, no fever CVS, Respiratory, GI, GU exams CVS, Respiratory, GI, GU exams

reported as normalreported as normal Back examBack exam

– InspectionInspection: normal: normal– PalpationPalpation: some pain in L1: some pain in L1– ROMROM: normal: normal– Some pain in right leg with straight leg Some pain in right leg with straight leg

raisingraising

Investigation in ClinicInvestigation in Clinic

Lumbar Spine X-rayLumbar Spine X-ray– Some age related degenerationSome age related degeneration

DiagnosisDiagnosis

Sciatica vs. Back strainSciatica vs. Back strain

Treatment: Treatment: – NSAIDSNSAIDS– Few days of bed restFew days of bed rest

The story continues…The story continues…

Mr. EC’s pain does not resolveMr. EC’s pain does not resolve More trials of various forms of pain More trials of various forms of pain

control failcontrol fail One month later Mr. EC awakens in One month later Mr. EC awakens in

the morning and has difficulty the morning and has difficulty supporting his weightsupporting his weight– Subjective leg muscle weaknessSubjective leg muscle weakness

Goes to HSC Emergency roomGoes to HSC Emergency room

In ERIn ER Patient has objective leg weakness Patient has objective leg weakness

on physical examon physical exam A very keen medical student does a A very keen medical student does a

rectal exam and discovers a large rectal exam and discovers a large nodular prostatenodular prostate

PSA: 45.0PSA: 45.0 MRI Spine…..MRI Spine…..

Spinal Cord CompressionSpinal Cord Compression

Malignant Epidural Spinal Cord Malignant Epidural Spinal Cord Compression (ESCC)Compression (ESCC)

Neoplastic invasion of the space Neoplastic invasion of the space between vertebrae and spinal cord between vertebrae and spinal cord (epidural invasion)(epidural invasion)– Usually from bone metastasesUsually from bone metastases

Compresses thecal sac of spinal cordCompresses thecal sac of spinal cord Frequent complication of malignancyFrequent complication of malignancy Can cause painCan cause pain Can cause irreversible loss of Can cause irreversible loss of

neurologic functionneurologic function

DefinitionDefinition

Any radiological indentation of the Any radiological indentation of the thecal sac thecal sac

Tip of the spinal cord lies at the L1 Tip of the spinal cord lies at the L1 vertebral levelvertebral level

Lumbosacral nerve roots form the Lumbosacral nerve roots form the cauda equinacauda equina

EpidemiologyEpidemiology

Many cases of unrecognized ESCCMany cases of unrecognized ESCC

Difficult to define incidenceDifficult to define incidence

Autopsy review studies suggest Autopsy review studies suggest around 5% of cancer patients die around 5% of cancer patients die with ESCCwith ESCC99

9. Barron, KD, Hirano, A, Araki, S, Terry, RD. Experiences with 9. Barron, KD, Hirano, A, Araki, S, Terry, RD. Experiences with metastatic neoplasms involving the spinal cord. Neurology 1959; metastatic neoplasms involving the spinal cord. Neurology 1959; 9:91. 9:91.

CausesCauses Metastatic tumor from any primary Metastatic tumor from any primary

sitesite Tumors with predilection to Tumors with predilection to

metastasize to spinal columnmetastasize to spinal column Prostate, breast, and lung carcinomaProstate, breast, and lung carcinoma

– 15-20% of cases15-20% of cases Renal cell, non-Hodgkin’s lymphoma, Renal cell, non-Hodgkin’s lymphoma,

or myelomaor myeloma– 5-10% of cases5-10% of cases

Vertebral metastases are more Vertebral metastases are more common than ESCCcommon than ESCC

Prostate cancerProstate cancer: 90%: 90% Breast CancerBreast Cancer: 74%: 74% Lung CancerLung Cancer: 45%: 45% LymphomaLymphoma: 29%: 29% Renal cellRenal cell: 29%: 29% GIGI: 25%: 25%

10. Posner, JB. Neurologic Complications of Cancer. FA Davis, 10. Posner, JB. Neurologic Complications of Cancer. FA Davis, Philadelphia, 1995 Philadelphia, 1995

ESCC can be initial presentation of a ESCC can be initial presentation of a malignancymalignancy– Around 20% of casesAround 20% of cases– In many cases diagnosis is made by In many cases diagnosis is made by

biopsy of the spinal lesionbiopsy of the spinal lesion

Spinal LocationSpinal Location1010

Thoracic spine: 60%Thoracic spine: 60% Lumbosacral spine: 30%Lumbosacral spine: 30% Cervical spine: 10%Cervical spine: 10%

Specific tumor predilection is difficult Specific tumor predilection is difficult to defineto define

Clinical FeaturesClinical Features

Important to recognizeImportant to recognize Early recognition leads to better Early recognition leads to better

outcomesoutcomes Efficacy of treatment depends most Efficacy of treatment depends most

on patient’s neurological function at on patient’s neurological function at presentationpresentation

Median time from symptoms to Median time from symptoms to diagnosis is around 2 monthsdiagnosis is around 2 months1111

More than half of patients who More than half of patients who present to hospital are non-present to hospital are non-ambulatoryambulatory

11. Husband, DJ. Malignant spinal cord compression: Prospective 11. Husband, DJ. Malignant spinal cord compression: Prospective study of delays in referral and treatment. BMJ 1998; 317:18. study of delays in referral and treatment. BMJ 1998; 317:18.

RED FLAGS…..RED FLAGS…..

First Red Flag:First Red Flag: Pain Pain Usually first symptomUsually first symptom1212

– 80-90% of the time80-90% of the time Usually precedes other neurologic Usually precedes other neurologic

symptoms by seven weekssymptoms by seven weeks– Increases in intensityIncreases in intensity

Severe local back painSevere local back pain Aggravated by recumbencyAggravated by recumbency

– Distension of venous plexusDistension of venous plexus May become radicularMay become radicular

12. Bach, F, Larsen, BH, Rohde, K, et al. Metastatic spinal cord 12. Bach, F, Larsen, BH, Rohde, K, et al. Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression. Acta Neurochir (Wien) 1990; in 398 patients with spinal cord compression. Acta Neurochir (Wien) 1990; 107:37. 107:37.

Second Red Flag:Second Red Flag: Motor Motor Weakness: 60-85%Weakness: 60-85%1313

At or above conus medularisAt or above conus medularis– Extensors of the upper extremitiesExtensors of the upper extremities

Above the thoracic spineAbove the thoracic spine– Weakness from corticospinal Weakness from corticospinal

dysfunctiondysfunction– Affects flexors in the lower extremitiesAffects flexors in the lower extremities

Patients may be hyperreflexic below Patients may be hyperreflexic below the lesion and have extensor the lesion and have extensor plantarsplantars

13. Greenberg, HS, Kim, JH, Posner, JB. Epidural spinal cord 13. Greenberg, HS, Kim, JH, Posner, JB. Epidural spinal cord compression from metastatic tumor: Results with a new treatment compression from metastatic tumor: Results with a new treatment protocol. Ann Neurol 1980; 8:361. protocol. Ann Neurol 1980; 8:361.

Weakness tends to be symmetricalWeakness tends to be symmetrical

Progressive weakness is followed by Progressive weakness is followed by lost of gait function then paralysislost of gait function then paralysis

The severity of weakness is greatest The severity of weakness is greatest with thoracic metastaseswith thoracic metastases

Third Red Flag:Third Red Flag: Sensory Sensory

Less common than motor findingsLess common than motor findings

Still present in majority of casesStill present in majority of cases

Ascending numbness and Ascending numbness and parathesiasparathesias

Fourth Red Flag:Fourth Red Flag: Bladder and Bladder and Bowel FunctionBowel Function

Loss is late findingLoss is late finding

Autonomic neuropathy presents Autonomic neuropathy presents usually as urinary retensionusually as urinary retension– Rarely sole findingRarely sole finding

Radiologic InvestigationRadiologic Investigation

Diagnosis depends on ability to Diagnosis depends on ability to demonstrate a mass compressing demonstrate a mass compressing the thecal sacthe thecal sac

Plain radiographs are not enoughPlain radiographs are not enough Historically this involved invasive Historically this involved invasive

proceduresprocedures Advent of MRI has allowed non-Advent of MRI has allowed non-

invasive diagnosisinvasive diagnosis Clinical examination is not reliable in Clinical examination is not reliable in

determining level of lesiondetermining level of lesion

Entire imaging of spine is idealEntire imaging of spine is ideal– Focused CT imaging can miss clinically Focused CT imaging can miss clinically

unapparent lesionsunapparent lesions

Myelography and MRI are better than Myelography and MRI are better than plain X-Rays, bone scans and CT for plain X-Rays, bone scans and CT for diagnosisdiagnosis

Plain Spine RadiographsPlain Spine Radiographs

Easiest and cheapestEasiest and cheapest

Need large bony destruction or Need large bony destruction or vertebral collapse to be diagnosticvertebral collapse to be diagnostic

High false negative rateHigh false negative rate

Not recommended to confirm Not recommended to confirm diagnosisdiagnosis

MRI vs. CT MyelographyMRI vs. CT Myelography

Both image thecal sac and display Both image thecal sac and display indentation and encirclingindentation and encircling

CT myelography involves a lumbar CT myelography involves a lumbar puncturepuncture– Contraindicated in brain metastases, Contraindicated in brain metastases,

thrombocytopenia, or coagulopathythrombocytopenia, or coagulopathy– Can diagnose leptomeningeal Can diagnose leptomeningeal

metastasesmetastases– Available in Winnipeg in middle of the Available in Winnipeg in middle of the

nightnight

MRIMRI Images whole spineImages whole spine

High detailHigh detail

Spares lumbar punctureSpares lumbar puncture

Patients in pain must lie stillPatients in pain must lie still

Roughly equivalent in terms of Roughly equivalent in terms of sensitivity and specificitysensitivity and specificity

Presently no large comparative Presently no large comparative studies b/c MRI in the US has become studies b/c MRI in the US has become so readily availableso readily available

MRI standard of care in centers that MRI standard of care in centers that have accesshave access

Bone ScanBone Scan

More sensitive than plain radiographMore sensitive than plain radiograph

Visualizes entire skeletonVisualizes entire skeleton

Can miss neoplasms that do not have Can miss neoplasms that do not have increased blood flowincreased blood flow

CT Scan aloneCT Scan alone

Does not visualize spinal cord and Does not visualize spinal cord and epidural space clearlyepidural space clearly

Intramedullary MetastasesIntramedullary Metastases

Less commonLess common

Often present with hemicord Often present with hemicord symptomssymptoms– Unilateral weakness below lesionUnilateral weakness below lesion– Contralateral diminution of pain and Contralateral diminution of pain and

temperature sensationtemperature sensation– Can progress to bilateral dysfunctionCan progress to bilateral dysfunction

Radiation MyelopathyRadiation Myelopathy

Can mimic ESCCCan mimic ESCC

MR imaging can make distinctionMR imaging can make distinction

MRI of epidural spinal cord compression in a MRI of epidural spinal cord compression in a women with past history of breast cancer.women with past history of breast cancer.

TreatmentTreatment

Treatment delays…….Treatment delays…….

2 month median delay in treatment 2 month median delay in treatment from onset of back painfrom onset of back pain1111

14 day delay in treatment from onset 14 day delay in treatment from onset of neurological symptomsof neurological symptoms1111

Why the delay?Why the delay?

Patient factorsPatient factors

General practitioner factorsGeneral practitioner factors

Hospital factorsHospital factors

EDUCATIONEDUCATION

Treatment ObjectivesTreatment Objectives

Pain controlPain control

Avoidance of complicationsAvoidance of complications

Preserve or improve neurological Preserve or improve neurological functionfunction

Pain managementPain management

CorticosteroidsCorticosteroids– Decrease edemaDecrease edema

OpiatesOpiates– Needed to decrease pain for comfort Needed to decrease pain for comfort

and examination purposesand examination purposes

Bed RestBed Rest

NoNo

NoNo

NoNo

NoNo

AnticoagulationAnticoagulation

Cancer is a hypercoaguable stateCancer is a hypercoaguable state High burden of tumor in metastatic High burden of tumor in metastatic

diseasedisease Possible value in prophylaxis against Possible value in prophylaxis against

venous thromboembolismvenous thromboembolism If patient not mobile subcutaneous If patient not mobile subcutaneous

heparin or compression devices is heparin or compression devices is indicatedindicated

Prevention of ConstipationPrevention of Constipation FactorsFactors

– Autonomic dysfunctionAutonomic dysfunction– Limited mobilityLimited mobility– Opiate analgesicOpiate analgesic

Risk of perforationRisk of perforation– Masked by corticosteroidsMasked by corticosteroids

Bowel regimen neededBowel regimen needed

CorticosteroidsCorticosteroids

Part of standard regimenPart of standard regimen

Limited data on benefit vs. side Limited data on benefit vs. side effectseffects

Many studies suggesting lower doses Many studies suggesting lower doses can be effectivecan be effective– No randomized trialsNo randomized trials

Corticosteroid RecommendationsCorticosteroid Recommendations High dose dexamethasone and half High dose dexamethasone and half

dose every three daysdose every three days

Pain with minimal neurological Pain with minimal neurological dysfunction can have lower dosedysfunction can have lower dose

Small asymptomatic lesions can Small asymptomatic lesions can forgo steroidsforgo steroids

Radiation TherapyRadiation Therapy

Definitive choiceDefinitive choice

Portal 8 cm widePortal 8 cm wide Centered on spineCentered on spine Extends one to two vertebral bodies Extends one to two vertebral bodies

above and below the epidural above and below the epidural metastasismetastasis

Relieves pain in most casesRelieves pain in most cases Post-neurological function usually Post-neurological function usually

determines responsedetermines response Response most associated with Response most associated with

tumor type and radiosensitivity; eg. tumor type and radiosensitivity; eg. lymphomalymphoma

Dosing 20 to 40 Gy in 5 to 20 Dosing 20 to 40 Gy in 5 to 20 fractionsfractions

PopularPopular– 30 Gy in 10 fractions30 Gy in 10 fractions

SurgerySurgery

Changing roleChanging role

Historically posterior vertebral Historically posterior vertebral decompression was donedecompression was done– No survival benefit with or without No survival benefit with or without

radiationradiation1515

15. Findlay, GF. Adverse effects of the management of malignant 15. Findlay, GF. Adverse effects of the management of malignant spinal cord compression. J Neurol Neurosurg Psychiatry 1984; spinal cord compression. J Neurol Neurosurg Psychiatry 1984; 47:761.47:761.

Better techniques today allow Better techniques today allow aggressive approachaggressive approach

Gross spinal tumor resection with Gross spinal tumor resection with vertebral reconstruction now possiblevertebral reconstruction now possible

Experienced surgeon requiredExperienced surgeon required

Recent controlled trial comparing Recent controlled trial comparing aggressive surgery followed by aggressive surgery followed by radiation vs. radiation aloneradiation vs. radiation alone1616

Improvement in surgery+radsImprovement in surgery+rads– Days remained ambulatory (126 vs. 35)Days remained ambulatory (126 vs. 35)– Percent that regained ambulation after Percent that regained ambulation after

therapy (56% vs. 19%)therapy (56% vs. 19%)– Days remained continent (142 vs. 12)Days remained continent (142 vs. 12)– Less steroid dose, less narcoticsLess steroid dose, less narcotics– TrendTrend to increase survival to increase survival

16. Patchell, R, Tibbs, PA, Regine, WF, et al. A randomized trial of 16. Patchell, R, Tibbs, PA, Regine, WF, et al. A randomized trial of direct decompressive surgical resection in the treatment of spinal direct decompressive surgical resection in the treatment of spinal cord compression caused by metastasis (abstract). proc Am Soc cord compression caused by metastasis (abstract). proc Am Soc Clin Oncol 2003; 22:1. Clin Oncol 2003; 22:1.

ChemotherapyChemotherapy

Can be successful in chemosensitive Can be successful in chemosensitive tumorstumors– Hodgkin’s lymphomaHodgkin’s lymphoma– Non-Hodgkin’s lymphomaNon-Hodgkin’s lymphoma– NeuroblastomaNeuroblastoma– Germ cellGerm cell– Breast cancer (hormonal manipulation)Breast cancer (hormonal manipulation)– Prostate cancer (hormonal Prostate cancer (hormonal

manipulation)manipulation)

BisphosphonatesBisphosphonates

RecommendedRecommended

Decrease pathologic fractures in Decrease pathologic fractures in bony diseasebony disease– Multiple myelomaMultiple myeloma– Breast cancerBreast cancer

PrognosisPrognosis

Median survival with ESCC is 6 Median survival with ESCC is 6 monthsmonths1414

Ambulatory patients with Ambulatory patients with radiosensitive tumors have the best radiosensitive tumors have the best prognosisprognosis

14. Sorensen, PS, Borgesen, SE, Rohde, K, et al. Metastatic epidural 14. Sorensen, PS, Borgesen, SE, Rohde, K, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer spinal cord compression. Results of treatment and survival. Cancer 1990; 65:1502. 1990; 65:1502.

Treatment DelayTreatment Delay

EducationEducation

EXPERIENCEEXPERIENCE

EducationEducation

EXPERIENCEEXPERIENCE

Case 3: Mrs. HCCase 3: Mrs. HC ID:ID: 75 year old female living alone 75 year old female living alone

with no significant past medical with no significant past medical historyhistory

EC:EC: brought to ER by paramedics brought to ER by paramedics after neighbor called b/c she was after neighbor called b/c she was found in her apartment unresponsivefound in her apartment unresponsive

No collateral historyNo collateral history

ExaminationExamination Fluctuating level of consciousnessFluctuating level of consciousness

Vitals normal, no feverVitals normal, no fever

DehydratedDehydrated

Coarse upper airway soundsCoarse upper airway sounds

No other pertinent findingsNo other pertinent findings

InvestigationsInvestigations

CBC normalCBC normal

Mildly elevated BUN and CrMildly elevated BUN and Cr

Normal LFTsNormal LFTs

Standard electrolytes normalStandard electrolytes normal

Concern of pneumoniaConcern of pneumonia

Chest x-ray ordered……Chest x-ray ordered……

Multiple Pulmonary MetastasisMultiple Pulmonary Metastasis

Calcium checkedCalcium checked– 4.54.5

HypercalcemiaHypercalcemia

SymptomsSymptoms

Usually nonspecificUsually nonspecific

Many times patients present with Many times patients present with very high calcium levelvery high calcium level

Most research done in Most research done in hyperparathyroidismhyperparathyroidism

GastrointestinalGastrointestinal Constipation is most commonConstipation is most common1515

– Exacerbated or confused with narcotic Exacerbated or confused with narcotic effectseffects

– Related to autonomic dysfunctionRelated to autonomic dysfunction AnorexiaAnorexia Vague abdominal painVague abdominal pain Rarely can lead to pancreatitisRarely can lead to pancreatitis

15. Heath, H 3d. Clinical spectrum of primary 15. Heath, H 3d. Clinical spectrum of primary hyperparathyroidism: Evolution with changes in medical practice hyperparathyroidism: Evolution with changes in medical practice and technology. J Bone Miner Res 1991; 6(Suppl 2):S63. and technology. J Bone Miner Res 1991; 6(Suppl 2):S63.

Renal DysfunctionRenal Dysfunction NephrolithiasisNephrolithiasis

– More common in hyperparathyroidismMore common in hyperparathyroidism Nephrogenic diabetes insipidusNephrogenic diabetes insipidus

– Defect in concentrating abilityDefect in concentrating ability– Polyuria and polydipsiaPolyuria and polydipsia

Chronic renal failureChronic renal failure– Longstanding high calciumLongstanding high calcium

Calcifcation, degeneration, and necrosis of Calcifcation, degeneration, and necrosis of tubulestubules

NeuropsychiatircNeuropsychiatirc

AnxietyAnxiety DepressionDepression Cognitive dysfunctionCognitive dysfunction

– DeleriumDelerium– PsychosisPsychosis– HallucinationsHallucinations– SomnolenceSomnolence– ComaComa

CardiovascularCardiovascular

Short QT intervalShort QT interval

Supraventricualr arrhythmiasSupraventricualr arrhythmias

Ventricular arrhythmiasVentricular arrhythmias

Physical FindingsPhysical Findings

Usually not specificUsually not specific

Dehydration secondary to diuresis Dehydration secondary to diuresis caused by the hypercalcemia caused by the hypercalcemia

Corneal deposition of calciumCorneal deposition of calcium– ““band keratopathy” on slit lamp examband keratopathy” on slit lamp exam

EpidemiologyEpidemiology

Occurs in about 10 to 20% of Occurs in about 10 to 20% of patients with cancerpatients with cancer

Both solid tumors and leukemiasBoth solid tumors and leukemias Most commonMost common

– BreastBreast– LungLung– Multiple myelomaMultiple myeloma

PathogenesisPathogenesis

Three mechanismsThree mechanisms

Osteolytic metastases with local Osteolytic metastases with local cytokine releasecytokine release

Tumor secretion of parathyroid Tumor secretion of parathyroid hormone-related protein (PTHrP)hormone-related protein (PTHrP)

Tumor production of calcitriolTumor production of calcitriol

Osteolytic MetastasesOsteolytic Metastases

Breast cancerBreast cancer Non-small cell lung cancerNon-small cell lung cancer Cytokines releasedCytokines released

– Tumor necrosis factorTumor necrosis factor– Interleukin-1Interleukin-1– Stimulate osteoclast precursor Stimulate osteoclast precursor

differentiation into mature osteoclastsdifferentiation into mature osteoclastsLeading to more bone breakdown and Leading to more bone breakdown and

release of calciumrelease of calcium

PTH-Related ProteinPTH-Related Protein Most common in patients with non-Most common in patients with non-

metastatic tumorsmetastatic tumors Called humoral hypercalcemia of Called humoral hypercalcemia of

malignancymalignancy Secretion of PTH itself is a rare eventSecretion of PTH itself is a rare event PTHrP binds to same receptor as PTH PTHrP binds to same receptor as PTH

and stimulates adeynylate cyclase and stimulates adeynylate cyclase activity activity – Increased bone resorptionIncreased bone resorption– Increases kidney calcium reabsorption Increases kidney calcium reabsorption

and phosphate excretionand phosphate excretion

CalcitriolCalcitriol

Hodgkin’s disease (mechanism in Hodgkin’s disease (mechanism in majority)majority)

Non-Hodgkin’s (mechanism in 1/3)Non-Hodgkin’s (mechanism in 1/3)

Usually responds to glucocorticoid Usually responds to glucocorticoid therapytherapy

DiagnosisDiagnosis

Clinical symptomology withClinical symptomology with– History of cancerHistory of cancer– Risk factors for cancerRisk factors for cancer– Suppressed PTHSuppressed PTH

Some centers can test for PTHrP to Some centers can test for PTHrP to confirm Dx of humoral hypercalcemiaconfirm Dx of humoral hypercalcemia

High PTHrP may predict response to High PTHrP may predict response to pamidronatepamidronate1616

– Less of a responseLess of a response

16. Gurney, H, Grill, V, Martin, TJ. Parathyroid hormonerelated 16. Gurney, H, Grill, V, Martin, TJ. Parathyroid hormonerelated protein and response to pamidronate in tumourinduced protein and response to pamidronate in tumourinduced hypercalcemia. Lancet 1993; 341:1611. hypercalcemia. Lancet 1993; 341:1611.

Malignancy must be ruled out in Malignancy must be ruled out in patients that present with a very patients that present with a very high calcium and no other obvious high calcium and no other obvious causecause

TreatmentTreatment

AimsAims

Lower serum calcium concentrationLower serum calcium concentration

Treat complications if presentTreat complications if present

Treat underlying diseaseTreat underlying disease

VolumeVolume Large volume of normal Saline Large volume of normal Saline

administrationadministration Expands intravascular volumeExpands intravascular volume Increases calcium excretionIncreases calcium excretion

– Inhibition of proximal tubule and loop Inhibition of proximal tubule and loop reabosrptionreabosrption

– Reduces passive reabsorption of calicumReduces passive reabsorption of calicum Follow fluid status b/c of danger of Follow fluid status b/c of danger of

fluid overloadfluid overload

Inhibition of Bone ResorptionInhibition of Bone Resorption

Three therapiesThree therapies– CalcitoninCalcitonin– BisphosphonatesBisphosphonates– Gallium nitrateGallium nitrate

Historical therapyHistorical therapy– Antitumor antibiotic plicamycin Antitumor antibiotic plicamycin

(mithramycin)(mithramycin)Multiple serious side effectsMultiple serious side effectsNo longer manufacturedNo longer manufactured

CalcitoninCalcitonin

Salmon calcitoninSalmon calcitonin Increases renal excretion of calciumIncreases renal excretion of calcium Decreases bone reabsorption by Decreases bone reabsorption by

interfering with osteoclast interfering with osteoclast maturationmaturation

Weak agentWeak agent Works the fastestWorks the fastest

BisphosphonatesBisphosphonates Adsorb to the surface of bone Adsorb to the surface of bone

hyroxyapatitehyroxyapatite Interfere with osteoclast activityInterfere with osteoclast activity Cytotoxic to osteoclastsCytotoxic to osteoclasts Inhibit calcium release from boneInhibit calcium release from bone Three commonly usedThree commonly used

– PamidronatePamidronate– Zoledronic acidZoledronic acid– Etidronate (1Etidronate (1stst generation, weaker) generation, weaker)

BisphosphonatesBisphosphonates More potent than calcitoninMore potent than calcitonin Maxium effect occurs in 2 to 4 daysMaxium effect occurs in 2 to 4 days Trend to use of IV zoledronic acid in Trend to use of IV zoledronic acid in

the acute situationthe acute situation Both are can be renal toxicBoth are can be renal toxic

– More potent than pamidronateMore potent than pamidronate– Administered over a shorter period of Administered over a shorter period of

time (15 minutes vs. 2 hours)time (15 minutes vs. 2 hours)

Prophylactic BisphosphonatesProphylactic Bisphosphonates

Pamidronate use in patients with Pamidronate use in patients with known lytic lesionsknown lytic lesions1717

– Less episodes of hypercalcemiaLess episodes of hypercalcemia– Less pathologic fracturesLess pathologic fractures– Less painLess pain– Less spinal cord compressionLess spinal cord compression– Less need for radiation or surgeryLess need for radiation or surgery

17. Hortobagyi, GN, Theriault, RL, Porter, L, et al for the Protocol 19 17. Hortobagyi, GN, Theriault, RL, Porter, L, et al for the Protocol 19 Aredia Breast Cancer Study Group. Efficacy of pamidronate in reducing Aredia Breast Cancer Study Group. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 1996; 335:1785. metastases. N Engl J Med 1996; 335:1785.

Newly discovered side effect…Newly discovered side effect…

Osteonecrosis of the jawOsteonecrosis of the jaw

Recent case reports of jaw bone Recent case reports of jaw bone necrosis in patients on pamidronatenecrosis in patients on pamidronate

EDUCATION neededEDUCATION needed

Gallium NitrateGallium Nitrate

EffectiveEffective

More potential for nephrotoxicityMore potential for nephrotoxicity

Rarely usedRarely used

DialysisDialysis Last resortLast resort

Dialysis fluid with little or no calcium Dialysis fluid with little or no calcium is effectiveis effective

Useful when patients can’t tolerate Useful when patients can’t tolerate large volume resuscitation large volume resuscitation

If calcium needs to be correct If calcium needs to be correct emergentlyemergently

Recommendations in symptomatic Recommendations in symptomatic situationsituation

Volume expansionVolume expansion

Salmon calcitoninSalmon calcitonin

IV zoledronic acid or pamidronateIV zoledronic acid or pamidronate

Close follow up of calcium level and Close follow up of calcium level and symptomssymptoms

Transitions in Transitions in TreatmentTreatment

ChemotherapyChemotherapy

Two rolesTwo roles

Direct treatment of cancerDirect treatment of cancer

Palliation of symptomsPalliation of symptoms

Palliative ChemotherapyPalliative Chemotherapy

Goal is not cureGoal is not cure GoalsGoals

– Control of tumorControl of tumor– Preservation of functionPreservation of function– Help tumor symptomsHelp tumor symptoms

PainPainDsypneaDsypneaPruritisPruritisPoor appetitePoor appetiteWeight lossWeight loss

Fine BalanceFine Balance Chemotherapy can be very toxicChemotherapy can be very toxic

Ratio: benefit vs. toxicityRatio: benefit vs. toxicity Host factors and tumor factorsHost factors and tumor factors

Delicate balance in palliative Delicate balance in palliative situationsituation

Want medications that affect tumor Want medications that affect tumor but do not heavily affect hostbut do not heavily affect host

Psychology of CancerPsychology of Cancer

Psychological evolution during Psychological evolution during cancer treatmentcancer treatment

Many people have fought very hard Many people have fought very hard with their diseasewith their disease

Chemotherapy for “relief” not “cure” Chemotherapy for “relief” not “cure” can be difficult concept for patientscan be difficult concept for patients

ART of medicineART of medicine

EvolutionEvolution

Chemotherapeutic protocols that Chemotherapeutic protocols that have less side effectshave less side effects

molecular targeted therapiesmolecular targeted therapies– Attack tumor specifically Attack tumor specifically – Less effect on hostLess effect on host

Breast cancerBreast cancer

Colon CancerColon Cancer

Prostate cancerProstate cancer

Lung cancerLung cancer

Breast CancerBreast Cancer Aromatase inhibitors for ER positive Aromatase inhibitors for ER positive

tumorstumors– Anastrozole, Letrozole, ExemestaneAnastrozole, Letrozole, Exemestane

Trastuzumab (Herceptin)Trastuzumab (Herceptin)– Humanized monoclonal antibody Humanized monoclonal antibody

targeting Her-2/neu protein on breast targeting Her-2/neu protein on breast cancer cellscancer cells

– Inhibits growth factor signal Inhibits growth factor signal transductiontransduction

– Tolerated quite wellTolerated quite well

Colon CancerColon Cancer Capecitabine (Xeloda)Capecitabine (Xeloda)

Oral drug that is transformed into 5-Oral drug that is transformed into 5-FU with three enzymatic reactionsFU with three enzymatic reactions– Final enzyme is at higher levels in tumor Final enzyme is at higher levels in tumor

cellscells– Contributes to drug’s less toxic side Contributes to drug’s less toxic side

effect profileeffect profileLess stomatitis, less myelosupressionLess stomatitis, less myelosupression

Targeted GI TherapiesTargeted GI Therapies

BevacizumabBevacizumab– Monoclonal antibody to Monoclonal antibody to vascular vascular

endotheial growth factor receptorendotheial growth factor receptor– Some cardiac toxicitySome cardiac toxicity

CetuximabCetuximab– Monoclonal antibody to Monoclonal antibody to human human

epidermal growth factor receptorepidermal growth factor receptor– Skin toxicitySkin toxicity

Prostate CancerProstate Cancer

LHRH analoguesLHRH analogues

Leuprolide (Lupron)Leuprolide (Lupron)

Goserelin (Zoladex)Goserelin (Zoladex)

Stop testosterone production with Stop testosterone production with limited side effectslimited side effects

Lung CancerLung Cancer

In stage IV disease patients who In stage IV disease patients who receive Cisplatin based doublet receive Cisplatin based doublet chemotherapy live longer and feel chemotherapy live longer and feel better than best supportive carebetter than best supportive care

Hard to balance side effectsHard to balance side effects

Gefitinib (Iressa)Gefitinib (Iressa)

Targets epidermal growth factor Targets epidermal growth factor receptor (tyrosine kinase small receptor (tyrosine kinase small molecule inhibitor)molecule inhibitor)

May have a role in the palliation of May have a role in the palliation of advanced non small cell lung cancer advanced non small cell lung cancer patientspatients

Palliative Care DebatePalliative Care Debate Do not accept any patient on Do not accept any patient on

“active” therapy“active” therapy This needs to be further elucidatedThis needs to be further elucidated Patients being palliated with Patients being palliated with

chemotherapy or targeted therapies chemotherapy or targeted therapies still have other palliative care issues still have other palliative care issues and needsand needs

Should a patient still on Xeloda for Should a patient still on Xeloda for breast or colon cancer not be breast or colon cancer not be admitted to St. Boniface 8A?admitted to St. Boniface 8A?

Thank youThank you

Any questions?Any questions?