The Optimal Dose Fractionation Schema for Malignant Extradural Spinal Cord Compression

Malignant spinal cord compression (MSCC) is one of the most dreaded complications of metastatic cancer. MSCC can be divided into intradural (intramedullary and leptomeningeal) and extradural (Malignant Extradural Spinal Cord Compression [MESCC]).^[1] Its natural history, if untreated, is usually one of relentless and progressive pain, paralysis, sensory loss, and sphincter dysfunction.^[2]

A population-based study of cancer patients reported that 2.5% (n = 3,458) of all cancer patients who died from their disease between 1990 and 1995 had at least one admission for MSCC.^[3] The incidence of MSCC varied widely by primary cancer site, from 7.9% in patients with myeloma to 0.2% in patients with pancreatic cancer.^[3]

In 1998 and again in 2005, our group published evidence-based clinical practice guidelines for the diagnosis and management of MESCC.^{[2] and [4]} The latter guideline was formally developed and approved through Cancer Care Ontario's Program in Evidence-Based Care (PEBC). The PEBC recommends that the guidelines be reviewed regularly and updated when potentially practice-changing data have been published. Since the last guideline, several randomized control trials have been published but, to our knowledge, no evidence-based guidelines have been issued.

Our objective was to review the literature published since the last guideline and summarize the data specifically pertaining to an optimal dose strategy for patients with MESCC treated with radiotherapy (with or without surgery). The literature search strategy was adopted from the initial review in 2005.^[4] Where the data were available, the summary focused on prospective studies.

Prognosis

A number of reports have been published to define the prognosis of patients with MESCC. Our group's research indicated that the prognosis overall was poor, with a median survival of 2.9 months after the diagnosis of MESCC.^[3] One of the strongest predictors of overall survival (OS) in our population-based study was tumor histology. Non-small-cell lung cancer had the worst median OS (1.5 months), and myeloma had the best median OS (6.7 months).

Other groups have shown quite a dramatic OS difference between patients who are able to ambulate posttreatment and patients who are not able to ambulate posttreatment. Maranzano et al^[5] documented a threefold difference in OS (10 vs. three months) based on ambulatory status posttreatment. In the Italian randomized studies, patients with favorable histology (breast, prostate, lymphoma, seminoma, or myeloma) and no abnormal neurology qualified for the good-prognosis group (the remaining patients were considered to have a poor prognosis).^{[6] and [7]}

Rades and colleagues have published a number of studies identifying several prognostic factors that were identified in several multivariate analyses.^{[8], [9], [10] and [11]} In a multicenter, international retrospective study of 1,852 patients treated with radiotherapy, the following factors were independently prognostic: histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MESCC, and time of developing motor deficits.^[9]

Rades, and colleagues went on to lead the development of a prognostic scoring system based on these factors and this patient data set. Total scores ranged between 20 and 45 points, and patients were divided into five groups. The six-month OS ranged from 4% to 99% (P < 0.001), with median OS estimated to range between two and 62 months from the worst to the best prognostic group (see [Table 1] and [Table 2]).