Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions.

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22-73% of the cases after whole brain radiotherapy, but the percentage of reirradiated patients is 3-10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status > 70, age < 65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an "in-field" recurrence of spinal metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An alpha/beta ratio of 1.9-3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.

Management of metastatic spinal cord compression.

Metastatic spinal cord compression, diagnosed in 3-7% of cancer patients, is one of the most dreaded complications of metastatic cancer. It is an oncologic emergency, which must be diagnosed early and treated promptly to achieve the best results and avoid progressive pain, paralysis, sensory loss and sphincter incontinence. Patients who are ambulatory at the time of the diagnosis have a higher probability of obtaining good response to treatment and a longer survival. In clinical practice, back pain accompanies metastatic spinal cord compression in most cases, even in patients with no neurologic deficits. Magnetic resonance imaging is the best tool for diagnosing metastatic spinal cord compression and is able to identify spinal cord compression in 32-35% patients with back pain, bone metastases and normal neurologic examination. Moreover, magnetic resonance imaging gives the extension of the lesion, can diagnose other unsuspected clinical metastatic spinal cord compression sites, and is useful for the radiation oncologist in defining the target volume. Radiotherapy is the treatment of choice in most cases, whereas surgery is advised only in selected patients (ie, if stabilization is necessary, if radiotherapy has already been given in the same area, when vertebral body collapse causes bone impingement on the cord or nerve roots, when there are diagnostic doubts, or when computed tomography-guided percutaneous vertebral biopsy cannot be performed). Laminectomy should be abandoned in favor of more aggressive surgery (ie, posterior, anterior, and/or lateral approach, tumor mass resection, and stabilization of the spine). Generally, radiotherapy must be administered 7-10 days after surgery. The optimal radiation schedule has not been defined. However, as recently suggested by some clinical trials, even the hypofractionated radiotherapy regimens are effective and can be used without increasing radiation-induced myelopathy. Moderate doses of dexamethasone should be used in the early phases of therapy. After radiotherapy, spinal recurrence is generally found in sites different from the first compression area. A close post-treatment follow-up is suggested using clinical parameters (pain, motor and sphincter function), and magnetic resonance imaging should be performed only when a second metastatic spinal cord compression and/or myelopathy are clinically suspected.