Higher Dose Irradiation for Malignant Spinal Cord Compression: Long-Term Results of the RAMSES-01 Trial

TL;DR

A higher dose radiotherapy regimen improves long-term spinal cancer control without increasing severe side effects in patients not undergoing surgery.

Contribution

Demonstrates long-term benefits of higher dose radiotherapy regimens for malignant spinal cord compression compared to standard doses.

Findings

Higher dose regimens (15 × 2.633 or 18 × 2.333 Gy) showed significantly better local progression-free survival at 2 and 3 years.

No radiation myelopathy or pathologic vertebral fractures were observed in any group.

Survival rates were not significantly different between the treatment groups.

Abstract

The RAMSES-01 trial compared two radiotherapy regimens, namely 15 × 2.633/18 × 2.333 Gy (phase 2 cohort) and 10 × 3.0 Gy (control group), in patients with malignant spinal cord compression (MSCC) not receiving upfront surgery and expected to be long-term survivors. Patients of the phase 2 cohort had significantly better local progression-free survival (LPFS) after 1 year. The question of whether this superiority would be present also after 2 or 3 years led to the present study. According to propensity-adjusted Cox regression analyses, LPFS was significantly better after 15 × 2.633 or 18 × 2.333 Gy at 2 years and 3 years when compared to 10 × 3.0 Gy. In both groups, radiation myelopathy or pathologic vertebral fractures were not reported. Given the limitations of this study, 15 × 2.633 or 18 × 2.333 Gy may be an alternative option for patients with MSCC and longer expected survival.

Despite the increasing popularity of upfront decompressive surgery, there are still patients with malignant spinal cord compression (MSCC) and expected longer-term survival receiving irradiation alone. In these patients, local progression-free survival (LPFS) may be improved with doses beyond the commonly applied regimen of 10 × 3.0 Gy. A prospective phase 2 trial (RAMSES-01) investigated the benefit of two regimens, 15 × 2.633 and 18 × 2.333 Gy, compared with a 10 × 3.0 Gy (historical control). Patients in the phase 2 cohort had significantly better local progression-free survival (LPFS) after 1 year. Since recurrent MSCC-related motor weakness is a serious situation, it must be avoided as long as possible. In this respect, it is important to know whether the superiority of 15 × 2.633 and 18 × 2.333 Gy found in the RAMSES-01 trial still exists after 2 or 3 years. This led to the current study. In the phase 2 group, 2- and 3-year LPFS rates were 93.1% and 93.1%, respectively, and survival rates were 54.2% and 36.1%, respectively. According to propensity-adjusted Cox regression analyses, radiotherapy regimens in the phase 2 cohort resulted in significantly better LPFS at 2 (p = 0.017) and 3 (p = 0.013) years. In contrast, survival was not significantly different (p = 0.251 and p = 0.288, respectively). Radiation myelopathy and pathologic vertebral fractures were not observed in any group. Given the limitations of this study, irradiation 15 × 2.633 or 18 × 2.333 Gy may be an alternative option for patients with MSCC and longer expected survival treated with irradiation alone.

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