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Radiotherapy for Metastatic Spinal Cord Compression

Dirk Rades, MD Professor and Chair Department of Radiation Oncology University of Lübeck, Germany. Radiotherapy for Metastatic Spinal Cord Compression. Metastatic Spinal Cord Compression. Lesion of dorsal elements. Lesion of vertebra. Prasad et al. Lancet Oncol 2005.

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Radiotherapy for Metastatic Spinal Cord Compression

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  1. Dirk Rades, MD Professor and Chair Department of Radiation Oncology University of Lübeck, Germany Radiotherapy for Metastatic Spinal Cord Compression

  2. Metastatic Spinal Cord Compression Lesion of dorsal elements Lesion of vertebra Prasad et al. Lancet Oncol 2005 MSCC in 5-10% of all cancer patients most common primaries: Breast-Ca (~25%) Prostate-Ca (~20%) Lung-Ca (~20%) Myeloma (10-15%) Renal Cell Cancer (~10%) Localization: cervical <10% thoracic 60-80% lumbar 15-30%

  3. “True“ MSCC = Motor Deficits => Poor Survival Prognosis Year N pts. Median OS (mos.) Sorensen et al. 1990 149 2.3 Helweg-Larsen et al. 1995 107 3.4 Rades et al. 2001 131 5 Hoskin et al. 2003 102 3.5 Maranzano et al. 2005 276 4 Overall Treatment Time ?

  4. Schedule Time N Pts. 1 x 8 Gy 1 day 261 5 x 4 Gy 1 week 279 10 x 3 Gy 2 weeks 274 15 x 2.5 Gy 3 weeks 233 20 x 2 Gy 4 weeks 257 Evaluation of five radiation schedules and prognostic factors for MSCC in a series of 1,304 patients Rades et al., JCO 2005

  5. Improvementof Motor Deficits

  6. SCORE-1: Long-course (10x3 Gy, 15x2.5 Gy, 20x2 Gy) vs. Short-course RT (1x8 Gy, 5x4 Gy) Particularly important for long-term survivors ! Rades et al., ASCO 2009 + IJROPB 2011

  7. Survival-Score (N=1,852) Rades et al., Cancer 2008

  8. 5x4 Gy vs. 10x3 Gy (randomized SCORE 2 - Trial) Rades et al., JCO 2016

  9. 5x4 Gy vs. 10x3 Gy (randomized SCORE 2 - Trial) Rades et al., JCO 2016

  10. Matched-Pairs (N=242): 1x8 Gy vs. 5x4 Gy (≤35 points) Rades et al., IJROBP 2015

  11. Matched-Pairs (N=410): 1x8 Gy vs. 5x4 Gy (all patients) Matched-Pair Analysis (1:1): (age, gender, ECOG, tumor, N vertebrae, bone mets, visc. mets, interval FD-MSCC, ambulatory st., time developing motor deficits) Local Control of MSCC Overall Survival Rades et al., unpublished

  12. In addition to RT: Corticosteroids Effective ? => Yes Appropriate Dose ??

  13. SCORE-1 Study: Bisphosphonates Rades et al., IJROBP 2011

  14. In addition to RT:Decompressive Surgery surgery plus 10 x 3 Gy (N=50) vs. 10 x 3 Gy alone (N=51) ability to walk after treatment: 42/50 (84%) vs. 29/51 (57%) p=0.001 maintaining ambulatory status:median 122 vs. 13 days p=0.003 overall survival:median 4.2 vs. 3.3 months p=0.033 Surgery only for selected patients (10-15%): KPS  70, OS  3 mos., no paraplegia > 48 hrs., 1 spinal segment, no myeloma • 10 years to accrue(not all eligible patients included ?) • 10% more ambulatorypatients than in other series • small numberof patients (statistical power ?) • surgery-related complications: primary 12%; salvage 40% Patchell et al., Lancet 2005

  15. Surgery + RT vs. RT alone [N=324] Matched-Pair Analysis (1:2): (age, gender, ECOG, tumor, N vertebrae, bone mets, visc. mets, interval FD-MSCC, ambulatory, time developing motor deficits, RT) S + RT RT alone P better motor function 27% 26% 0.92 1-year local control 90% 91% 0.48 1-year survival 47% 40% 0.50 Rades et al., JCO, 2010

  16. Recurrence after Short-course RT Re-RT for MSCC(appears safe, if BED120 Gy2) Rades et al., IJROBP 2005, CANCER 2008

  17. Recurrence after Long-course RT Surgery, if possible and indicated

  18. Recurrence after Long-course RT - if Surgery is not possible - Re-RT ? => high precision RT Also an Option for Less Radiosensitive Tumors ?

  19. Less Radiosensitive Tumors Dose Escalation Rades et al., IJROBP, 2011

  20. Less Radiosensitive Tumors: RS/SBRT

  21. RS/SBRT: Late Toxicity - Vertebral Fractures Yamada, IJROBP 2008 N=93 IG-IMRT 1 x 24 (18 - 24) Gy 2% (EQD2 = 82 – 141 Gy) Rose, JCO 2009 N=62 IG-IMRT 1 x 24 (18 - 24) Gy 39% (EQD2 = 82 – 141 Gy) Garg, Cancer 2012 N=61 RS 1 x 16 - 24 Gy 21% (EQD2 = 66 – 141 Gy) Jawad, JNS 2016 N=594 RS/SBRTmedian 1 x 20 Gy 6% (EQD2 = 100 Gy) Chang, Spine 2016 review of 38 studies 14%

  22. RS / SBRT: Spinal Cord Tolerance risk of myelopathy <1% RTOG 06-31: Dose Constraints for SF-RS: Spinal cord 5-6 mm cranial / caudal to target: 10% < 10 Gy 0.35 ml < 10 Gy 0.035 ml < 14 Gy Cauda equina: 5 ml < 14 Gy 0.035 ml < 16 Gy Sahgal et al., IJROBP 2010: 1 x 10 Gy (EQD2: 30 Gy) = safe Kirkpatrick et al., IJROBP 2010: 1 x 13 Gy (EQD2: 49 Gy) 3 x 6.7 Gy (EQD2: 43 Gy)

  23. surgery indicated and possible Surgery not indicated / not possible intermediate radiosensitivity very radiosensitive tumors (lymphoma, myeloma, germ cell tumors) MSCC (multidisciplinaryevaluation) less radiosensitive tumors SBRT ? (studies) prognosis ≤2 months prognosis 3-6 months prognosis >6 months systemic therapy? surgery + long-course RT [Corticosteroids, Bisphosphonates] SBRT [Corticost., Bisphosph.] Single Fraction [Corticosteroids] or BSC Short-course RT [Corticosteroids] Long-course RT [Corticosteroids, Bisphosphonates] Patientswith MSCC require an individual (personalized) treatmentapproach !

  24. Thank You Very Much for your Attention and Best Regards from Lübeck !

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