Oncologic Emergencies and Paraneoplastic Syndromes

SUPERIOR VENA CAVA SYNDROME

Superior vena cava syndrome (SVCS) is a common occurrence in cancer patients and can lead to life-threatening complications such as cerebral or laryngeal edema. Although most commonly resulting from external compression of the vena cava by a tumor, SVCS can also stem from nonmalignant causes in cancer patients.

Etiology

Malignant causes

Primary intrathoracic malignancies are the cause of SVCS in approximately 87%–97% of cases. The most frequent malignancy associated with the syndrome is lung cancer, followed by lymphomas and solid tumors that metastasize to the mediastinum.

Lung cancer SVCS develops in approximately 3%–15% of patients with bronchogenic carcinoma, and it is four times more likely to occur in patients with right- vs left-sided lesions.

Metastatic disease Breast and testicular cancers are the most common metastatic malignancies causing SVCS, accounting for > 7% of cases. Metastatic disease to the thorax is responsible for SVCS in ~3%–20% of patients.

Nonmalignant causes

Thrombosis The most common nonmalignant cause of SVCS in cancer patients is thrombosis secondary to venous access devices (see chapter 43).

Other nonmalignant causes include cystic hygroma, substernal thyroid goiter, benign teratoma, dermoid cyst, thymoma, tuberculosis, histoplasmosis, actinomycosis, syphilis, pyogenic infections, radiation therapy, silicosis, and sarcoidosis. Some cases are idiopathic.

Signs and symptoms

Classic symptoms Patients with SVCS most often present with complaints of facial edema or erythema, dyspnea, cough, orthopnea, or arm and neck edema. These classic symptoms are seen most commonly in patients with complete obstruction, as opposed to those with mildly obstructive disease.

Other associated symptoms may include hoarseness, dysphagia, headaches, dizziness, syncope, lethargy, and chest pain. The symptoms may be worsened by positional changes, particularly bending forward, stooping, or lying down.

Common physical findings The most common physical findings include edema of the face, neck, or arms; dilatation of the veins of the upper body; and plethora or cyanosis of the face. Periorbital edema may be prominent.

Other physical findings include laryngeal or glossal edema, mental status changes, and pleural effusion (more commonly on the right side).

Diagnosis

It is important to establish the diagnosis and underlying etiology of SVCS, since some malignancies may be more amenable to specific treatment regimens than others. In the majority of cases, the diagnosis of SVCS is evident based on clinical examination alone.

The following diagnostic procedures may aid in establishing the diagnosis of SVCS and its etiology: chest x-ray, bronchoscopy, limited thoracotomy or thoracoscopy, contrast and radionuclide venography, Doppler ultrasonography, CT (especially contrast-enhanced spiral CT), and MRI.

Prognosis

The prognosis of SVCS depends on the etiology of the underlying obstruction. A review by Schraufnagel showed the average overall survival after the onset of SVCS to be 10 months, but there was wide variation (± 25 months) depending on the underlying disease, with an average survival of 7.6 months. This duration was not significantly different from the survival duration of 12.2 months in patients presenting with SVCS as the primary manifestation of the disease. Thoracic malignancy, the most common cause of SVCS, had a poor prognosis of < 5 months.

Treatment

Treatment includes radiotherapy, chemotherapy, thrombolytic therapy and anticoagulation, expandable wire stents, balloon angioplasty, and surgical bypass.

Most patients derive sufficient relief from obstructive symptoms when treated with medical adjuncts, such as diuretics and steroids (see section on "Adjunctive medical therapy"), so they can tolerate a work-up to determine the etiology of SVCS. In some instances, it is appropriate to delay treatment for 1–2 days if necessary to establish a firm tissue diagnosis.

Radiotherapy and chemotherapy

Both radiotherapy and chemotherapy are treatment options for SVCS, depending on the tumor type. The specific drugs and doses used are those active against the underlying malignancy.

Life-threatening symptoms, such as respiratory distress, are indications for urgent radiotherapy. A preliminary determination of the treatment goal (potentially curative or palliative only) is necessary prior to the initiation of treatment, even in the emergent setting.

Radiation therapy is the standard treatment of non—small-cell lung cancer (NSCLC) with SVCS. Recent studies suggest that chemotherapy may be as effective as radiotherapy in rapidly shrinking SCLC. Chemoradiation therapy may result in improved ultimate local control over chemotherapy alone in SCLC and non-Hodgkin lymphoma. Retrospective reviews of patients with SCLC have reported equivalent survival in patients with or without SVCS treated definitively with chemoradiation therapy.

Reasonable palliative courses can range from 2,000 cGy in 1 week to 4,000 cGy in 4 weeks. Curative regimens can range from 3,500 to 6,600 cGy based on histology. If indicated, more rapid palliation may be achieved by delivering daily doses of 400 cGy up to a dose of 800–1,200 cGy, after which the remainder of the appropriate total dose can be given in more standard daily fractions of 180 to 200 cGy. Some European investigators have used doses as high as 600 cGy 1 week apart in elderly patients.

Anticoagulation and thrombolysis

Anticoagulation for SVCS has become increasingly important due to thrombosis related to intravascular devices. In certain situations, the device remains in place. Both streptokinase and urokinase have been used for thrombolysis, although urokinase has been more effective in lysing clots in this setting. Urokinase is given as a 4,400-U/kg bolus followed by 4,400 U/kg/h, whereas streptokinase is administered as a 250,000-U bolus followed by 100,000 U/h. The use of thrombolytic therapy is controversial for catheter-related thrombosis, however.

Stenting

Placement of an expandable wire stent across the stenotic portion of the vena cava is an appropriate therapy for palliation of SVCS symptoms when other therapeutic modalities cannot be used or are ineffective. Use of stents is limited when intraluminal thrombosis is present.

Other interventional treatments

Balloon angioplasty and surgical bypass have also been used in appropriate patients but are rarely indicated. Balloon angioplasty may be considered in patients with SVCS, significant clinical symptoms, and critical superior vena cava obstruction demonstrated by angiography. Surgical bypass is usually limited to patients with benign disease; however, for a select group of patients with SVCS, bypass may be an important aspect of palliative treatment. Other palliative efforts may be considered prior to bypass in this patient population.

Adjunctive medical therapy

Medications that may be used as adjuncts to the treatments described above include diuretics and steroids.

Diuretics may provide symptomatic relief of edema that is often immediate although transient. The use of diuretics is not a definitive treatment, and resulting complications may ensue, such as dehydration and decreased blood flow. Loop diuretics, such as furosemide, are often used. Dosage depends on the patient's volume status and renal function.

Steroids may be useful in the presence of respiratory compromise. They are also thought to be helpful in blocking the inflammatory reaction associated with irradiation.

Dosage depends on the severity of clinical symptoms. For severe and significant respiratory symptoms, hydrocortisone, 100–500 mg IV, may be administered initially. Lower doses every 6–8 hours may be continued. Tapering of the steroid dosage should begin as soon as the patient's condition has stabilized. Prophylactic gastric protection is advised during steroid administration.