SUPERIOR VENA CAVA SYNDROME: A CONCISE OVERVIEW

SUPERIOR VENA CAVA SYNDROMEcomplete or partial resolution ofsymptoms within a few days of theprocedure. 46 In a series of 76 patientswith SVCS treated with Wallstents,100% reported symptomaticimprovement within 48 hours, and90% remained symptom free untildeath. 47 In patients with completeSVC obstruction, a success rate of85% was reported by Crowe andcolleagues. 36 Given these encouragingresults, several authors haverecommended stent therapy asfirst-line treatment in SVCS, especiallyfor patients with intense dyspnea,encephalopathy, cyanosis, orextensive edema. 48,49Stent complications are relativelyuncommon, occurring inabout 10% of cases. 50 In rare instances,migration due to inaccuratestent placement occurs. 44,46There also have been isolated casereports of heart failure, right atrialpuncture, and pulmonary edema.Oudkerk and colleagues reportedone stent migration and three cardiacarrhythmias in their 22-patientcase series. 51 Other reported complicationsinclude fever, cellulitis atthe access site, and pain during ballooninflation. 36,38,51–53There is no consensus regardingthe use of anticoagulant therapy asan adjuvant to stent placement inSVCS, and adjuvant therapies differfrom one medical center to another.Many providers, however,choose to administer intravenousheparin prior to and during the procedure.In cases in which the bloodflow is brisk and the vessel is large,aspirin may be enough to preventclot formation. 46 Periproceduralthrombolysis generally is reservedfor patients whose SVC occlusionis caused by a thrombus. Somepractitioners use warfarin for threeto six months after stenting, but theduration of anticoagulation can bevaried based on the individual situation.52,54 There also may be a rolefor clopidogrel after stenting forSVCS, but the data on this use arevery limited at this time and thedrug is not currently FDA approvedfor this indication.TREATING THEUNDERLYING DISEASEMalignancyWhen the underlying cause ofSVCS is a chemosensitive tumor(such as small-cell lung cancer,lymphomas, or mediastinal germcell tumors), chemotherapy is thepreferred initial treatment. Mostpatients with small-cell lung cancerdemonstrate a response (eitherpartial or complete) within a coupleof weeks of starting chemotherapy.55 Additional therapy usingconsolidation local radiotherapyshould be considered, particularlyfor a large mediastinal mass orlarge-cell lymphomas. 16 For tumorsthat are extremely sensitive tochemotherapy, such as lymphomasor germ cell tumors, there may be arisk of tumor lysis syndrome at theinitiation of treatment.Radiation is still the principaltherapy for most cases of SVCS ofmalignant origin, and it representsan effective initial modality formany such patients. 56 In order toprevent possible radiation-inducededema, high dose steroids shouldbe given concurrently, followed bygradual weaning. More than 80% ofpatients with non-small cell lungcancer begin to show improvementwithin one to three weeks of radiotherapy,with a median therapy durationof four weeks. 15,17It’s a standard practice for patientswith SVCS undergoing radiationtherapy to be given large dailyfractions of 350 to 400 cGy for thefirst three or four days, followed byreduction to a more conventionaldaily fraction of 180 to 200 cGy forthe remainder of the therapeuticcourse. This is based on studiesshowing quicker symptom reliefwith initial high dose therapy whencompared with conventional doses.In a retrospective review of 125 patientstreated for SVCS secondaryto malignant disease, Armstrongand colleagues found that 70% ofpatients treated initially with highdose radiation therapy (three dailyfractions of 300 to 400 cGy) experiencedgood symptomatic relief inless than two weeks, comparedwith 56% of patients treated withconventional doses (five weeklyfractions of 200 cGy). 15 In addition,Rodrigues’ hypofractionated regimenof 800 cGy once per week forthree weeks yielded a partial orcomplete response in more than90% of patients. 57There was no real difference inultimate symptomatic relief, however,between initial high dose andconventional daily dose radiationschedules according to Marder’s review.58 Considering the propensityof high dose radiotherapy to causeacute dysphagia, some radiationoncologists prefer to use conventionaldoses throughout the treatmentcourse in patients with SVCS.ThrombosisAnticoagulant treatment is indicatedfor SVC thrombosis resultingin obstruction. Although data arelimited, studies suggest a benefitwith either unfractionated heparinor low molecular weight heparin(LMWH), using the same regimensthat are given to patients with deepvenous thrombosis (DVT) of theleg. LMWH has the advantages ofsubcutaneous administration andno required monitoring of coagula-NOVEMBER 2004 • FEDERAL PRACTITIONER • 83

SUPERIOR VENA CAVA SYNDROMEtion parameters. Fibrinolytic therapymay be considered for acute,symptomatic, thrombotic SVC obstruction,but it may impart an increasedrisk of bleeding comparedwith conventional anticoagulation.Pulmonary emboli may occur in15% to 20% of patients with SVCthrombosis and should be suspectedif respiratory symptoms developor worsen.After initial therapy, anticoagulationshould be continued with warfarinto achieve an internationalnormalized ratio of 2 to 3, as is thecase for the treatment of leg DVT.There are no available studies toguide the duration of oral anticoagulationtherapy in this setting,though at least six months wouldbe prudent and indefinite treatmentshould be considered if the catheteris not removed.When a central venous catheteris the culprit of thrombotic SVC obstruction,the question of whetherto remove the catheter is a difficultone, in which the risk of continuedor recurrent thrombosis must beweighed against the future need forcentral venous access. Some researchhas indicated that LMWH orvery low, fixed dose warfarin (1mg/day) can help prevent catheterrelatedthrombosis safely, 59–62 andbased on these findings, the AmericanCollege of Chest Physiciansrecommends such prophylaxis forpatients with cancer who have indwellingcentral venous catheters. 63Many of these studies were small,however, and more research isneeded before a firm conclusion onthe clinical value of this approachcan be reached.Indications for surgerySurgical therapy is reserved forrare instances of complete SVCocclusion, radiotherapy or chemotherapyfailure, or thrombosis ofvenous collaterals. Aggressive surgicaloptions include bypass procedures(which reroutes the venousblood flow to the right atrium) anden bloc SVC removal. Surgeryis contraindicated in patients inwhom collaterals have decompressedthe upper compartmentveins and those with bulky mediastinaldisease.TREATING RECURRENT DISEASERoughly 10% to 20% of patientswith lung cancer who receive maximumradiation therapy for SVCSexperience recurrent SVC obstructionin one to 16 months. 64 Radiationfailures are due to tumorrecurrence, obstructive thrombosis,or radiation-induced fibrosis. 65In such cases, percutaneous stentplacement can be valuable, relievingsymptoms within 72 hours inapproximately 80% of patients. 66Recurrence of venous obstructionand return of symptoms occursin up to 45% of patientswho’ve had a stent placed. 46 Varioustherapeutic options are availablefor recurrent obstructiondepending on individual circumstances,including thrombolysis,restenting, clot aspiration, or balloonangioplasty. 46PROGNOSISThe prognosis of patients withSVCS is related primarily to theprognosis of the underlying malignantdisease. Lymphomas andgerm cell tumors are potentiallycurable with combination chemotherapy.Since most cases of SVCSare associated with lung cancer,however, the prognosis is generallypoor. Nevertheless, with appropriatetreatment, patients may experiencesubjective symptomaticimprovement within a week—which is much sooner than thetime it takes for objective responsesto become apparent (generallyone to three weeks). In astudy by Egelmeers and colleagues,the majority of patients with nonsmallcell lung cancer (64%) experiencedsubjective relief of SVCSsymptoms within three days of radiationtherapy initiation, and morethan half of the patients with smallcelllung cancer (54%) experiencedrelief between the fourth and thefourteenth days. 67According to Maddox and colleagues,the most common causeof death in patients with SVCS secondaryto small-cell lung cancer isdisease progression, and the mostimportant prognostic factorsare disease extent, pretherapyperformance status, and age. 29Schraufnagel reported an averagesurvival time of 10 months fromSVCS onset in patients with malignantdisease, with wide variationdepending on the primary tumor. 12Patients exhibiting symptomatic reliefwithin 30 days had a significantlybetter survival rate thanthose who did not. 12 Life expectancywas as short as less thanfive months for thoracic cancers. 12Egelmeers and colleagues foundthe median survival of patientswith SVCS to be six months, withone-year survival rates of 35% and18% for non-small cell and smallcelllung cancer, respectively. 67 Inthe study by Armstrong and colleagues,one-year survival rates inpatients with lymphoma, small-celllung cancer, and non-small celllung cancer were 41%, 24%, and17%, respectively. 15 Generally, meanposttreatment survival in SVCS issix to seven months.The presence of SVCS at thetime of cancer diagnosis doesn’t alwaysmean a worse prognosis.84 • FEDERAL PRACTITIONER • NOVEMBER 2004

SUPERIOR VENA CAVA SYNDROMESome studies, in fact, have shownthe opposite: Wurschmidt and colleaguesreported a median survivalof 16.1 months in patients withsmall-cell lung cancer and SVCS,compared with 13.7 months inthose with no SVCS. 68 Urban andcolleagues noted a similar—thoughnonsignificant—trend. 55By contrast, Chen and colleaguesnoted that SVCS portends agrim prognosis when associatedwith malignancy: Patients withnon-small cell lung cancer andSVCS had a median survival of sixmonths, whereas those withoutSVCS had a median survival of ninemonths. 17 In a separate study conducteda few years later, Chen andcolleagues concluded that patientswith SVCS as the initial manifestationof malignant disease had apoor prognosis compared to thosewho developed SVCS later. 69A higher incidence of brainmetastasis has been reported in patientswith small-cell lung cancerand SVCS in comparison to thosewith no SVCS. 55,68,70 For instance,Urban and colleagues observed a22% incidence of brain metastasisin patients with small-cell lung cancerwho presented with SVCS,compared with 11% in those whohad no SVCS at presentation. 55SUMMING UPSVCS is a common complication ofmalignancy, which is associatedmost frequently with lung cancer. Itis usually is not an emergency unlessthere is airway compromise. A histologicdiagnosis should be establishedbefore initiation of therapy,which should be individualizedbased on the tumor type, symptomseverity, and presence of concomitantproblems (such as thrombosis).Survival generally depends onthe nature of the tumor, with fewpatients actually dying of SVCSitself. Proper management can reducedistressing symptoms and improvequality of life.●The opinions expressed herein arethose of the authors and do notnecessarily reflect those of thesponsors, Federal Practitioner,Quadrant HealthCom, Inc., theU.S. government, or any of itsagencies. Please review completeprescribing information for specificdrugs or drug combinations—includingindications,contraindications, warnings, andadverse effects—before administeringpharmacologic therapy topatients.REFERENCES1. Ahmann FR. A reassessment of the clinical implicationsof the superior vena caval syndrome.J Clin Oncol. 1984;2:961–969.2. Fincher RM. 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Jpn J Clin Oncol.1995;25(2):32–36.70. Van Houtte P, de Jager R, Lustman-Marechal J,Kenis Y. Prognostic value of the superior venacava syndrome as the presenting sign of smallcell anaplastic carcinoma of the lung. Eur JCancer. 1980;16:1447–1450.CALL FORMANUSCRIPTSFederal Practitioner welcomessubmission of clinical reviewarticles in all areas of healthcare. Topics of particularinterest include:ArthritisAutoimmune disordersBlood disordersSickle-cell diseaseCardiovascular disordersCellulitisColecystitisDermatologic disordersGastrointestinal disordersBiliary tract diseaseGastroenteritisGastroesophageal refluxdiseaseUlcerative colitisGenitourinary disordersGoutGynecolgic disordersHIVHormone replacementtherapyImmunizationInfectious diseasesMusculoskeletal disordersNative American healthNeurologic disordersTraumatic brain injuryPain managementPreventive medicineObesityPsychiatric disordersRespiratory diseaseSurgeryThyroid diseaseTropical medicineFor submission requirements,see our Guidelines for Authorson page 91 of this issue.86 • FEDERAL PRACTITIONER • NOVEMBER 2004