Malignant related superior vena cava (SVC) syndrome Manit Sae-teaw B.Pharm, BCP, BCOP Grad dip in Pharmacotherapy Faculty of pharmaceutical sciences Ubon Ratchathani University 1
Outline Introduction Etiology Pathophysiology Clinical evaluation Treatment Therapeutic goal Supportive care Specific treatment Pharmacist role Conclusion 2
Introduction Superior vena cava (SVC) syndrome result from any condition that lead to obstruction blood flow to SVC Oncology emergency??? Due to rapid formation of collateral vessel formation Except : severe laryngeal edema, severe cerebral edema and hemodynamic compromise 3
Etiology Preantibiotic era Syphilitic thoracic aortic aneurysms Fibrosing mediastinitis Postantibiotic era Malignancy (60-80%) Recently Incidence form thrombosis (20-40%) 1. Wilson LD, et al. N Eng J Med. 2007;356:1862. 2. Schechter MM. Am J Med Sci. 1954;227:46. 3. Yellin A, et al. Am Rev Respir Dis. 1990;141:1114. 4. Rice TW, et al. Medicine (Baltimore). 2006;85:37. 5. Chee CE, et al. Nat Clin Pract Cardiovasc Med. 2007;4:226. 4
Etiology Commonly classified into Extra-vascular compression Lymphadenopathy or mass compression Intra-vascular compression Thrombosis venous obstruction 5
Distribution of malignancies causing SVC syndrome Ref : McCurdy MT, et al. Crit Care Med. 2012;40:2212. 6
Lung cancer and SVC syndrome SVC 2-4% of patients with lung cancer SCLC : more common (10%) SCLC develops and grows rapidly in central rather than peripheral airway NSCLC : Less common (<2%) More NSCLC patients (85%) in lung cancer More patients with SVC in NSCLC 1. NCCN. 2013. http://www.nccn.org. 2. Rowell NP, et al. Clin Oncol (R Coll Radiol). 2002;14:338. 7
Lymphoma and SVC syndrome Non-Hodgkin lymphoma (NHL) Incidence 2-4% of patient Diffuse large cell and lymphoblastic lymphoma are the most common type Hodgkin lymphoma Rarely cause Despite common presentation with mediastinal lymphadenopathy 1. Armstrong BA, et al. Int J Radiat Oncol Phys. 1987;13:531. 2. Perez-Soler R, et al. J Clin Oncol 1984;2:260. 8
Pathophysiology Superior vena cava carries blood from upper extremities to the heart 1/3 of venous return to the heart When the SVC is obstructed Central venous pressure increased to 20-40 mm Hg (Normal 2-8 mm Hg) Compensate with blood flow to collateral vascular network will be occurred Ref : Wilson LD, et al. N Eng J Med. 2007;356:1862. 9
Clinical presentation Frequency Range Facial edema 82 60-100 Arm edema 46 14-75 Distended neck vein 63 27-86 Distended chest vein 53 38-67 Facial plethora 20 13-23 Visual symptoms 2 0-3 Dyspnea 54 23-74 Cough 54 38-70 Hoarseness 17 15-20 Stridor 4 0-5 Syncope 10 8-13 Headache 9 6-11 Dizziness 6 2-10 Confusion 4 0-5 Obtundation 2 0-3 Ref : Wilson LD, et al. N Eng J Med. 2007;356:1862. 10
Imaging study Chest radiograph 84% abnormal chest film Mediastinal widening and pleural effusion Computer tomography (CT) scan Contrast-enhanced chest CT (most useful) Identify venous blockade and cause of obstruction Venography Gold standard for venous thromboembolism dx Identify venous blockade but not cause of obstruction Magnetic resonance imaging (MRI) Alternative approach for patient who CT scan can not be used 11
Tissue diagnosis Cytology method Description Diagnostic yield Sputum Easy, non invasive 50% Thoracethesis For pleural effusion 50% Bronchoscope Invasive 75% Mediastinoscope Invasive >90% 1. Mineo TC, et al. Ann Thorac Surg. 1999;68:223. 2. Rice TW, et al. Respirology. 2006;11:299. 3. Dosios T, et al. Chest. 2005;128:1551. 4. Schraufnagel DE, et al. Am J Med. 1981;70:1169. 12
Clinical evaluation Evaluation SVC syndrome diagnosis Severity evaluation Cause of SVC obstruction Diagnosis confirmation Information Clinical presentation Clinical presentation Patient history Patient history Imaging study Tissue diagnosis 13
Grade Category Definition Radiographic superior vena cava obstruction 0 Asymptomatic Absence of symptoms 1 Mild Edema in head or neck, cyanosis, plethora 2 Moderate 3 Severe Edema in head or neck with functional impairment (mild dysphagia, cough, mild or moderate impairment of head, jaw or eyelid movements, visual disturbances caused by ocular edema) Mild or moderate cerebral edema (headache, dizziness) or mild/moderate laryngeal edema or diminished cardiac reserve (syncope after bending) 4 Lifethreatening Significant cerebral edema (confusion, obtundation) or significant laryngeal edema (stridor) or significant hemodynamic compromise (syncope without precipitating factors, hypotension, renal insufficiency) 5 Fatal Death 14
Therapeutic goal Alleviate symptoms Prevent complication Treatment underlying cause Life expectancy in cancer patients with SVC syndrome average 6 months Depend on type of cancer Ref : Wilson LD, et al. N Eng J Med. 2007;356:1862. 15
Supportive care management Elevate the patient s head to decrease hydrostatic pressure Oxygen therapy if dyspnea or tachypnea IV should be administered through dorsal foot vein Diuretic (loop diuretic) are commonly used Study in 107 patients with SVC syndrome 1 Compare glucocorticoids, diuretic, neither therapy Rate of clinical improvement is similar (84% overall) 1. Schraufnagel DE, et al. Am J Med. 1981;70:1169. 16
Supportive care management Corticosteroid recommended in Steroid responsive tumor : Lymphoma or thymoma 1 Reduce swelling (laryngeal edema) if radiation is the treatment method Initial dose : Dexamethasone 4 mg IV q 4-6 hrs 1. Rowell NP, et al. Clin Oncol (R Coll Radial). 2002;14:338. 17
Radiotherapy Radiotherapy prior tissue diagnosis Deferring therapy until full diagnostic workup not affect treatment outcome 1 Radiotherapy prior biopsy may obscure the histology diagnosis 2 Increase intravascular stent used 3 Control symptoms faster Lower recurrent rate Not interfere histology diagnosis 1. Schraufnagel DE, et al. Am J Med. 1981;70:1169. 2. Loeffler JS, et al. J Clin Oncol. 1986:4; 716. 3. Rowell NP, et al. Clin Oncol (R Coll Radial). 2002;14:338. 18
Radiotherapy Radiotherapy after tissue diagnosis Recommended used in radiosensitive tumor Response onset : 72 hr after treatment Rowell NP, et al. 1 Systematic review study in SVC syndrome SCLC : RR 78%, Recurrent rate 17% NSCLC : RR 63%, recurrent rate 19% Ahmann FR. 2 Detect 85% response after RT Complete SVC patency only 14% 1. Rowell NP, et al. Clin Oncol (R Coll Radial). 2002;14:338. 2. Ahmann FR. J Clin Oncol. 1984;2:961. 19
Chemotherapy SCLC, NHL, Germ cell tumor Chemo-radiosensitive tumor SVC syndrome is not poor prognosis factor Response rate (SVC) 80% (improve within 1-2 wks) NSCLC Less chemosensitive tumor SVC is poor pronosis factor Response rate (SVC) 40% Ref : Rowell NP, et al. Clin Oncol (R Coll Radial). 2002;14:338. 20
Intravascular stent Intravascular stent prior tissue diagnosis Response onset within hours (edema resolve within 48-72 hours) 1 Recommended for severe SVC syndrome (Grade 4 symptoms) Severe laryngeal edema Severe cerebral edema Hemodynamic compromise 1. Tanigawa N, et al. Acta Radiol. 1998;39:669. 21
Intravascular stent Intravascular stent after tissue diagnosis For alleviate symptoms (Can not treat cancer) Recommended for Chemo-radio resistant tumor (Mesothelioma) Chemo-radiosensitive tumor with severe symptoms Rowell NP, et al. 1 Systematic review study in SVC syndrome CMT or RT Stent RR Relapse RR Relapse SCLC 77% 17% 95% 11% NSCLC 60% 19% 1. Rowell NP, et al. Clin Oncol (R Coll Radial). 2002;14:338. 22
Intravascular stent Antithrombotic after intravascular stent No data and evidence-based support Short term use (3 months) If thrombolytic is use, anticoagulants are recommended (Warfarin 1 mg/day to target INR < 1.6) If thrombolytic is not use, antiplatelet are recommended (Clopidofrel 75 mg/day + aspirin 81 mg/day) Long term use If thrombolytic is use anticoagulants are recommended 23
Surgery Surgical bypass grafting Relative few complications Rarely performed because success of endovascular stent Surgical resection 1,2 Increase rate of morbidity and mortality Except malignant thymoma and thymic carcinoma Chemo-radiation resistant 1. Shimizu N, et al. J Thorac Cardiovasc Surg. 1992;103:414. 2. Charokopos N, et al. Thorac Cardiovasc Surg. 2007;55:267. 24
Ref : Yu JB, et al. J Thorac Oncol. 2008;3:811. 25
Ref : Yu JB, et al. J Thorac Oncol. 2008;3:811. 26
Pharmacist role Patient history to support multidisciplinary team for SVC diagnosis Provide medication information to generate therapeutic plan for individualized patient Provide information regarding to route of IV administration Monitoring efficacy and toxicity after medication treatment Patient counseling 27
Conclusion SVC syndrome is the obstruction of SVC Intravascular and extravascular cause Cancer is the most common cause Diagnosis by clinical presentation Therapeutic goal is to alleviate symptoms and treatment underlying cause Grade 4 severity need emergency treatment Non-emergency condition need to identify and treatment following cause of SVC syndrome 28
Thank you for your attention 29