ICORG 07-11: A Phase II Trial Evaluating the Efficacy of a Radiobiological Based Re-Irradiation Strategy for Patients with Malignant Spinal Cord Compression.

TPS317 Background: Malignant Spinal Cord Compression (MSCC) represents the 2nd most common cancer- related neurological complication, with an estimated 1 to 6% lifetime risk for all cancer patients (pts). Radiotherapy (RT) is broadly used in treatment of MSCC, and has been occasionally proposed in context of re-irradiation. Due to increased survival and use of RT, the number of pts developing MSCC in previously irradiated areas is increasing (Thirion, 2008). Preclinical and clinical data suggest that the spinal cord maximal tolerable cumulative radiation dose (MTD) depends on the received radiation schedules (total dose, dose-per-fraction [#]) and interval between treatments (Nieder, 2006). The efficacy and toxicity, especially the risk of radiation-induced myelopathy (RIM), of re-irradiation for MSCC has not been prospectively evaluated. The objective of ICORG 07-11 is to establish the efficacy and safety of a radiobiological based re-irradiation strategy in pts with MSCC occurring in a previously irradiated area. Methods: Patient eligibility criteria are: histologically proven malignancy, MRI-established non-operable MSCC, previous RT to the MSCC area delivering a Biological Effective Dose (BED) ≤ 90 Gy2, KPS > 30 and age > 18. The present accrual is 5 pts (n=25). Based on hypothesized spinal cord MTD BED ≤ 100 Gy2 and ≤ 130 Gy2 for treatment intervals of respectively ≤ 6 and > 6 months, RT is delivered up to MTD (using 3 Gy/# RT schedule; from 18 Gy/6# to 30Gy/10#). A Phase II trial Gehan's two-stage design is used, with efficacy and toxicity interim analysis. The Stage 1 sample size is 14 pts. The continuation rules are minimum overall response rate (defined as improved/stable mobility) ≥ 20% and Nieder-defined low and intermediate risk group RTOG/SOMA RIM grade > 2 incidences of respectively < 3% & < 25%. The second stage sample size is 11 pts (Response rate estimation with SE <0.1). The primary end-point is efficacy, evaluated by changes in Tomita mobility scale score (baseline, week 1 and 5, then 3-monthly). The secondary end-points are Quality of Life (EORTC/QLQ-C15-PAL, v1.0) and nonspinal radiation-induced toxicity (RTOG criteria). No significant financial relationships to disclose.