Treatment of Metastatic Epidural Spinal Cord Compression: The Goldilocks Principle

Loblaw and Mitera are to be congratulated for their ongoing efforts to provide systematic guidelines in the palliative management of patients with malignant spinal cord compressions (MSCC). Highlighted in this review are recent reports that can help determine an appropriate radiotherapy (RT) dose. Loblaw and Mitera explore the various considerations important to the multidisciplinary team when reviewing treatment options. As a result of a lack of significant progress in the management of MSCC, unanswered questions remain.

When a patient is given a poor prognosis, it is difficult to modulate treatment to alleviate the side effects of MSCC and the risk of toxicity and to improve quality of life. However, many symptoms arising from a tumor's mass require some measure of tumor response to therapy. Such is the case with the neurologic compromise that arises from MSCC.

Standard palliative RT doses alleviate the pain associated with MSCC. Reversing and maintaining ambulation can be limited and is likely dependent upon achieving sufficient tumor response to therapy. RT dose intensification may provide effective tumor response and disease control at the MSCC site, preventing future loss of neurologic function. However, there are major impediments for such studies: (1) the RT toxicities associated with the use of large traditional nonconformal RT fields often used to expedite care, (2) the time required (of the patient especially), and (3) the limited prognosis of the palliative patient.

In their review, Loblaw and Mitera identify the importance of applying a risk stratification approach to guide future treatment decisions and clinical trials based on various validated scoring systems. Risk stratification offers several advantages. While these include a more homogeneous study population for future studies, it allows for the identification of a cohort of patients for whom alternative end points for palliative management can potentially be evaluated. Foremost is the issue of whether RT dose intensification improves pain control, tumor response, and disease control. There are several lines of evidence that support a possible dose–response relationship.

Maranzano et al ^[1] reported that even in poor-prognosis patients there was improvement in the in-field local control rates. In a relatively favorable cohort of MSCC patients prospectively treated and evaluated, Rades et al ^[2] reported significantly improved 12-month local control rates when comparing a short course of RT (8 Gy in one fraction or 20 Gy in five fractions) to a longer course of RT (30 Gy in 10 fractions) ( P = 0.032). Univariate analysis demonstrated that local control rates were only significantly associated with the RT fractionation schedule that was used. Given the potential for selection bias, the finding that the radiation schedule continued to maintain statistical significance in the multivariate analysis (relative risk = 1.49, P = 0.035) offers greater confidence that a dose–response relationship may exist. These findings are consistent with this group's retrospective analysis when higher total doses of 30 Gy in 10 fractions or 40 Gy in 20 fractions were compared to 8 Gy in one fraction or 20 Gy in five fractions. ^[3] Thus, higher total doses appear to be associated with improved local control rates at the site of MSCC and may be particularly important for favorable-prognosis patients who are at risk of developing local progression and further neurologic compromise. The local control improvements appear to be the main reason that there was an improvement in progression-free survival rates. ^[2]

In contrast, Rades et al ^[2] did not find an association between higher RT doses and motor function. This may be due to the ongoing neurologic compression seen with tumor responses even at doses of 30 Gy in 10 fractions. Decompressive surgery followed by 30 Gy in 10 fractions is superior to RT alone with select patients benefiting from improved ambulatory function for a longer period of time. ^[4] However, other sites of MSCC or nonvertebral bone metastases can affect motor function as well and should be taken into consideration.

Modern advancements in administering palliative RT provide an opportunity for favorable therapeutic outcomes. Using image guidance, modern hypofractionated courses of RT can reduce the number of radiation fractions while achieving a higher cytotoxic effect. As a result, many of the barriers for RT dose escalation in the MSCC patient can now be overcome.

Several centers have initiated dedicated palliative care clinical services designed around the unique needs of the palliative patient. Even though analgesics can provide prompt pain relief, the literature suggests it is the addition of palliative RT that provides for the most effective and long-lasting pain relief. ^[5]

Loblaw and Mitera point out that the optimal fractionation schedule is not clear at this time. However, the use of 30 Gy in 10 fractions appears reasonable. The suggestion of a dose–response relationship for improved local control rates at the MSCC site also leads to questions about the optimal RT dose following surgical decompression in the favorable-prognosis patient.

The Radiation Therapy Oncology Group (RTOG) is currently conducting a prospective phase II/III RTOG 0631 study of stereotactic body radiotherapy (SBRT) for MSCC patients using image guidance to provide greater confidence in the treatment setup and dose delivered. ⁶ The randomization is 16 vs 8 Gy, both in a single fraction. However, the primary end point is pain control, with secondary end points that do not consider the local control rates at the site of the MSCC but do consider the time to pain relief, which is often overlooked. Moreover, the eligibility criteria permit a spectrum of cancer types, including unfavorable lung cancers. These considerations are likely to limit the ability to determine if 16 Gy may offer other benefits aside from improved pain control.

For the unfavorable-prognosis patient, it is equally imperative that the right dose and the right fractionation are given. Nonconformal approaches delivering hypofractions such as 8 Gy in one fraction may offer the best option, especially when symptom management is the goal of the treatment. If local control is an important treatment goal, higher total doses may be of benefit; but the patient's prognosis must be carefully evaluated. Hypofractionation appears to be the best approach. Is this achieved with 16 Gy in two fractions? ^[1] Whether this requires higher total doses remains an unanswered question at this time.

In the end, while risk stratification tools can aid in deciding the optimal dose and fractionation for the MSCC patient, the best tool we have is to actively communicate with our patients. Helping the MSCC patient understand the potential goals and burdens of any treatment approach can be invaluable in deciding on the right fractionation schedule.