Radiation Oncology/Palliation/SVC Syndrome

Superior Vena Cava Syndrome Histologic diagnosis is essential for choosing appropriate therapy Epidemiology ~15,000 cases in US per year Caused by invasion/compression of SVC by mass in right lung, lymph nodes, mediastinal structures, or thrombosis within the SVC Historically syphilitic thoracic aortic aneurysms, fibrosing mediastinitis (histoplasmosis) and other untreatable infections were frequent causes Currently (since 1980s) malignancy is the most common cause ~ 70-90% Non-malignant causes (10-30%): Thrombosis (indwelling vascular devices), fibrosing mediastinitis, postradiation fibrosis Of all SVC cases related to malignancy Presenting symptom in previously undiagnosed malignancy in 60% of cases NSCLC in 50%, SCLC in 25% and NHL in 10% 2-4% of Lung cancers cause SVC 2-4% of NH Lymphomas (DLBCL and Lymphoblastic lymphoma) cause SVC Hodgkins lymphoma is rarely a cause, in spite of its predilection for mediastinum Prognosis on average is 6 months life expectancy But approximately 10% to 20% survive longer than 2 years Survival of malignant SVC patients similar to survival of comparable tumor type/stage patients without it Etiology Malignancy (~65%) Tumor Type Proportion NSCLC 50% SCLC 22% Lymphoma 12% Metastatic cancer 9% Germ cell 3% Thymoma 2% Mesothelioma 1% Other cancers 1% Intra-vascular devices (~33%) Infections (rare) Anatomy Collateral veins arise from the azygos, internal mammary, lateral thoracic, paraspinous, and esophageal venous systems Clinical Presentation Symptoms may develop over weeks to months Dyspnea is most common presenting symptom Increased venous pressure Edema in torso, arms, neck, and head (exacerbated when lying down) Laryngeal edema, leading to cough, hoarseness, dyspnea, stridor, dysphagia Cerebral edema, leading to headaches, confusion, and coma Decreased venous return Hemodynamic compromise Development of collateral venous return Proposed grading system for superior vena cava syndrome (See 18670297) GradeCategoryIncidence %Definition 0Asymptomatic10Radiographic superior vena cava obstruction in the absence of symptoms 1 Mild 25 Edema in head or neck (vascular distention), cyanosis, plethora 2 Moderate 50 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) 3 Severe 10 Mild or moderate cerebral edema (headache, dizziness) or mild/moderate laryngeal edema or diminished cardiac reserve (syncope after bending) 4 Life-threatening 5 Significant cerebral edema (confusion, obtundation) or significant laryngeal edema (stridor) or significant hemodynamic compromise (syncope without precipitating factors, hypotension, renal insufficiency) 5 Fatal < 1 Death Workup CXR, CT Scan Consider: sputum cytology, pleural fluid cytology, bronchoscopy, mediastinoscopy, VATS Treatment Medical Management Elevate head to decrease hydrostatic pressure and cerebral edema Remove indwelling catheter (if secondary to thrombosis) Consider glucocorticoids (decadron 4mg q6), although risk is that it will obliterate existing histology in case first biopsy is insufficient Consider loop diuretics Anticoagulation benefit not clear, although some recommend thrombolysis followed by anticoagulation Radiation Therapy Emergent RT is no longer considered necessary if patient is stable and diagnosis is not established (7234887) RT prior to biopsy can obscure histologic diagnosis (3701390) Endovascular stents in severely symptomatic patients provide more rapid relief Consider Emergency RT (and endovascular stent) if Stridor from severe laryngeal edema Coma from cerebral edema RT dose/schedule Start RT as soon as possible. Initially use high-dose fractions (3-4 Gy) for 2 or 3 days if treating curatively to 60-70Gy, followed by standard 1.8-2 Gy/fx Not unusual to palliate with 3Gy x 10, or 4Gy x 5 or 2.5Gy x 15 Symptomatic relief can be apparent in 72 hours, complete relief can be seen by 2 weeks (78% SCLC, 63% NSCLC) However, SVC patency improvement only in 31%, so some symptom relief probably due to development of collateral circulation over time Many patients will recur symptomatically prior to death Consider Chemotherapy before or with RT if: SCLC, NHL & germ cell tumors In the absence of distant metastasis, aggressive management is indicated Symptomatic relief within the first 30 days might be a good prognostic factor Endovascular Stent Stent can be placed before tissue diagnosis (unlike RT) Results in rapid relief of symptoms ~ 90% patients report symptomatic relief (17546400) Indications to consider: Significant respiratory distress, although lymphomas and germ cell tumors respond rapidly to chemo and/or RT Post-RT recurrence Mesothelioma, since they don't respond well to chemo or RT Recurrence post-stent is < 40% (average is 13%) No evidence for durable benefit of angioplasty alone Chemotherapy Chemotherapy is initially preferred for SVC in SCLC, NHL & germ cell tumors with ~75% response Addition of RT can reduce recurrence of symptoms Review of 2 randomized trials and 44 single institution series showed no difference in symptom relief, DFS, and OS between RT only, chemo only, or chemo-RT Literature Meta-analysis, 2002 12555872 -- "Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review." (Rowell NP, Clin Oncol (R Coll Radiol). 2002 Oct;14(5):338-51.) 2 randomized and 44 nonrandomized studies reviewed. SVC present in 10% of patients with SCLC and 2% of patients with NSCLC Relief of SVCO: SCLC chemo 77% vs. RT 78%; NSCLC chemo 59% vs. RT 63%. Not related to RT fractionation schedule or chemo regimen Conclusion: Chemotherapy and RT are effective in some patients, stent may provide relief in higher proportion and more rapidly. Effectiveness of steroids uncertain Sao Paolo, 1999 (Brazil) Abstract "Neoadjuvant chemotherapy vs radiotherapy alone for superior vena cava syndrome (SVCS) due to non-small cell lung cancer (NSCLC): preliminary results of randomized phase II trial." (Pereira JR, Eur J Cancer 1999;35(Suppl 4):260. Randomized. Terminated early due to larger number of treatment-related deaths in chemo arm. 34 patients with NSCLC. Treated with immediate RT + cisplatin vs. cisplatin/epirubicin/vinblastine. Info from 12555872 Outcome: no difference in relief or survival, but larger number of treatment-related deaths in chemo-only arm Washington University, 1987 3558044 -- "Role of irradiation in the management of superior vena cava syndrome." (Armstrong BA, Int J Radiat Oncol Biol Phys. 1987 Apr;13(4):531-9.) Retrospective. 125 patients with SVC syndrome. Outcome: 80% good to excellent symptomatic relief. 2-week relief initial high dose (3-4 Gy/fx x3) 70% vs. low dose (2 Gy/fx) 56% (p=0.09). 1-year OS lymphoma 41%, SCLC 24%, NSCLC 17%. Combined chemo-RT didn't improve response, symptom relief or survival. Recurrence of SVC syndrome in 13% Toxicity: Minimal, dysphagia most common 26% London (UK)(no dates given) -- SCLC: chemo +/- RT Randomized. 37/366 patients with SCLC enrolled in trial of chemotherapy +/- RT presented with SVC obstruction. 9 relapsed during chemo and were not randomized. Induction chemotherapy (adriamycin + vincristine + cyclophosphamide alternating with cyclophosphamide + MTX) x4 cycles then randomized Arm 1) RT 40/20 AP/PA vs. Arm 2) continued chemotherapy. Both consolidated with 8 cycles of chemotherapy 1983 6310812 -- "Treatment of obstruction of the superior vena cava by combination chemotherapy with and without irradiation in small-cell carcinoma of the bronchus. (Spiro SG, Thorax. 1983 Jul;38(7):501-5.) Outcomes: After induction chemo, 21/37 (57%) CR, 10/37 (27%) PR of SVC symptoms. Median OS identical. Conclusion: Chemo alone effective for SVC; no benefit for consolidative RT induction chemo x4 cycles Oklahoma/Virginia -- high dose RT vs. nitrogen mustard + RT Randomized. 28 patients with SVC syndrome, 22 completed treatment. Arm 1) nitrogen mustard 0.4 mg/kg, then in 3-8 days RT 40-50 Gy in 1.5-2.0 Gy/fx vs. Arm 2) RT only (4 Gy/fx until drop in venous pressure at least 30 mm H2O or 20 Gy, then 2 Gy/fx for total 40-50 Gy), diuretics as necessary. Tumor + 1cm margin. Delivered by 2 MeV Van de Graaff unit. 1969 4898825 -- "Treatment of malignant superior vena caval obstruction. A randomized study." (Levitt SH, Cancer. 1969 Sep;24(3):447-51.) Outcome: Time to venous pressure drop (NS), relief of symptoms (NS), duration of relief (NS), recurrence (NS), OS (NS) Toxicity: Combined arm more severe complications Conclusion: No difference between groups, suggest initially high daily dose Review 2007 17476012 -- "Clinical practice. Superior vena cava syndrome with malignant causes." (Wilson LD, N Engl J Med. 2007 May 3;356(18):1862-9.)