# Radiation Oncology/Palliation/SVC Syndrome

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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 PMID 18670297) :
| Grade | Category | Incidence % | Definition |
| 0 | Asymptomatic | 10 | Radiographic 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 (PMID 7234887)
** RT prior to biopsy can obscure histologic diagnosis (PMID 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 (PMID 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 PMID 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 PMID 12555872
** Outcome: no difference in relief or survival, but larger number of treatment-related deaths in chemo-only arm
* Washington University, 1987 PMID 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 PMID 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 PMID 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 PMID 17476012 -- "Clinical practice. Superior vena cava syndrome with malignant causes." (Wilson LD, N Engl J Med. 2007 May 3;356(18):1862-9.)