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Reirradiation and Primary Treatment Spine C ases IAEA Singapore SBRT Symposium

Reirradiation and Primary Treatment Spine C ases IAEA Singapore SBRT Symposium. Yoshiya (Josh) Yamada MD FRCPC Department of Radiation Onology Memorial Sloan Kettering Cancer Center. Mechanisms of CNS Damage. Direct injury to normal cells Endothelial apoptosis

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Reirradiation and Primary Treatment Spine C ases IAEA Singapore SBRT Symposium

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  1. Reirradiation and Primary Treatment Spine CasesIAEA Singapore SBRT Symposium Yoshiya (Josh) Yamada MD FRCPC Department of Radiation Onology Memorial Sloan Kettering Cancer Center

  2. Mechanisms of CNS Damage • Direct injury to normal cells • Endothelial apoptosis • Oligodendroglial cells most vulnerable • 10-20Gy x 1 causes apoptosis within hours • Schwann cells most resistant • Poor DS repair of mature neurons and precursors • Inflammation from activated glial cells and monocyte infiltration • Vascular injury • Endothelial apoptosis within hours and BBB disruption • P53 dependent phenomenon • Increased VEGF • Immune hypersensitivity response • Antigens released by injured glial cells induce hypersensitivity response.

  3. Spinal Cord Radiation Injury From: Posner J, Neurologic Complications of Cancer, p 525

  4. Progressive Myelopathy • Demyelination, necrosis, BBB disruption • 12-50 months post XRT • Slowly progressive symptoms • Brown Sequard syndrome with paraethesia and weakness in one side and decrease in pain/temp in side, progressing to transverse myelitis • Progressive weakness, hyperactive reflexes, loss of position and vibration, pain and temp intact • Decreased motor conduction velocity • CSF usually N, or increased protein. • MRI: Cord swelling and patchy enhancement

  5. Spinal Cord Recovery: Rodent CordNieder et al. Semin Rad Oncol 2000

  6. Reirradiation and Myelopathy: BED ModelingNeider et al IJROBP 2005 • Literature search for myelopathy after reirradiation • N = 40 with complete dosimetric data available • 11 cases of myelopathy • Doses converted to BED equivalents • (α/β 2 or 4 - 50Gy/25 = 75Gy4 or 100 Gy2) • No Myelopathy was seen if: • Total BED < 135.5 Gy2 • Initial XRT <102 Gy2 • >2 months between courses of XRT • Low risk of myelopathy if: • Total dose < 135.5Gy2, each course < 98 Gy2 • 6 months between treatments • Underscores the need for cord sparing techniques

  7. Reirradiation x 3

  8. Reirradiation x 3: MSKCC

  9. Table 3: Patient Characteristics and Outcomes Reirradiation x 3: Results

  10. Quantec: Spinal Cord ReirradiationKirkpatrick et al IJROBP 2010 • Most data on reirradiation with a minimum interval of at least 6 months • Volume effects: • At 2 Gy equivalents, full circumference cord dose, at least 25% recovery at 6 months • With SBRT (partial cord) 13Gy/1 or 20Gy/3 < 1% risk of myelopathy • Impact of systemic therapy unknown

  11. Yucatan Mini Pig ReirradiationMedin et al. IJROBP 2010 • 23 mature mini pigs received 3000cGy/10 • Single Fraction Spine SRS one year later

  12. Pig Cord ED50 • 96% calculated recovery after 3000cGy/10 after one year.

  13. Pig Cord Reirradiation Histopathology • No changes at 14-16 Gy • 18-20 Gy changes limited to small foci of demyelination • 22-24 Gy extensive tissue damage including grey matter infarction • Pigs reirradiated with SRS one year after 3000cGy/10 no different that pigs receiving de novo SRS.

  14. MSKCC Normal Tissue Constraints for Reirradiation

  15. Salvage Spine Radiation • Local control of spine metastases after conventional radiation is 20-60% • Durability of symptom control for conventionally fractionated spine XRT is low (median 2.5 – 3 months-Patchell and Maranzano) • Systemic therapy is often less effective in treating spine metastases • Recurrence is often highly symptomatic • Surgical salvage can be morbid and recurrence rates are high without adjuvant therapy

  16. Rationale for Hypofractionation • By definition, recurrent tumors are resistant to conventional XRT • Hypofractionation represents a different radiobiologic approach to treatment • IGRT is the best vehicle to deliver high dose radiation near the spinal cord/esophagus

  17. Salvage XRT for Cord CompressionRades Red Journal 2005 • N = 62 • ESCC after XRT failure • 6 months median time to repeat XRT • Cumulative BED 80-102 Gy2 • 40% improved, 45% stable, 15% worse • No myelopathy

  18. SRS vs Conventional XRT • Differences in volumes • Steep dose fall off • Single fraction or hypofractionation vs. conventional fraction sizes

  19. Radiation Myelopathy After Spine SRS • N=6/1075 • Mean of 6.3 months (2-9 months) • 2 patients had prior RT (39.6Gy/22, 50.4Gy/28 70 and 80 months prior) • 20-21 Gy/2 fractions, 20Gy/2-14Gy/2 cord Dmax • Both had prior chemotx • Progression to paraplegia, walker dependent. Gibbs et al, Neursurgery, 2009

  20. Salvage SRS After Spine XRT FailureGerzsten et al. Spine 2007 • N = 393 • Prior XRT = 3Gy x10 or 2.5Gy x14 • 20Gy x1 (12.5-25Gy) mean dose to 80% • Median FU = 21 months (3-53) • 88% local control, 86% dural pain palliation • No cases of myelitis

  21. Hypofractionated Salvage Spine IGRT: 400cGyx5 vs 600cGyx5 Local ControlDamast et al. IJROBP 2010 • N = 97 • Median FU= 14.7 months • 38 LF • Overall LF = 30% 40% p=0.04 23%

  22. MD Anderson: Salvage IGRTGarg et al, Cancer 2011 • N =63 lesions • 16 LF • Median FU 13 months • Prior XRT < 45 Gy • Prior XRT > 3months • 600cGyx5 or 900cGyx3 • Mean cord dose: 10 Gy Local Control

  23. Reirradiation Spinal Cord Summary • Animal data suggests that reirradiation of the spinal cord is feasible • Significant repair of radiation does occur • Dose dependent • Volume dependent • Time dependent • Clinical data is of poor quality • Repeat radiotherapy is effective palliation • Risk of myelitis is low • SRS is safe after conventional radiation failure

  24. Spine Reirradiation Summary • There is mounting evidence that: • Spinal cord is likely capable of radiation repair over time • Cord recovery occurs after prior XRT • 6-12 months • Pig data: Steep complication curve slope! • Spine reirradiation is safe and an effective salvage treatment. • Both single fraction or hypofractionated • 75% durable successful salvage rates

  25. Recommendations • Careful and meticulous treatment planning and delivery is crucial • Accurate cord deliniation (iemyelogram) • Minimum of 6 months between initial and salvage XRT for spinal cord recovery • Maximum cord doses should be less than 17.5 Gy/3 fractions • Detailed and well documented discussion with patients about potential complications

  26. Compression/Burst FractureAxial Load Pain • 64 year old male with stage IV thyroid cancer • Prior I 131 treatment • T6 burst fracture • Systemic disease otherwise well controlled • Increased pain with sitting to standing • No myelopathy

  27. Compression/Burst FractureAxial Load Pain

  28. Compression/Burst FractureAxial Load Pain • Axial Load Pain: No gross instability • Percutaneous cement augmentation • Vertebroplasty • Kyphoplasty

  29. 18 Reduction of T6-L1 Kyphosis T6 T6 Post 18  Pre 36 L1

  30. Melanoma L5 with mechanical radiculopathy • 54 year old male with long standing melanoma • 4 month history of progressive lower back pain, 3 week history of pain radiating down the right leg, laterally below the knee to ankle in L5 distribution • Motor intact • Pain worse with weight bearing, 8/10 • Visceral metastases to liver and lung, “stable” • KPS 80, able to tolerate any treatment • No prior RT

  31. Treatment options?

  32. 34 year old right handed female with MPNST • Delivered her first child 8 weeks ago • Neck pain for 12 weeks • Metastatic work up negative • Pain radiates down right neck and shoulder • Progressive weakness right triceps (4/5)

  33. Subaxial Cervical

  34. Treatment Options?

  35. Renal Cell Carcinoma 52 y.o. RCC Sutent chemotherapy Prior RT: 30 Gy/10 C8-T1 Visceral Metastases No other bone lesions Exam: Right C8 radiculopathy No myelopathy Medical Problems: CASHD HTN Diabetes N: Functional Radiculopathy O: RT-resistant tumor M: No instability S: Tolerate any treatment

  36. Prostate Carcinoma 60 y.o. Known Hx: Prostate Hormone refractory, no chemo Bone metastases Exam: T6 pin level Intact Proprioception Lower Extremities 3/5 Medical Problems: CASHD: Pacemaker HTN

  37. Subaxial Cervical • 56 year old with stage IV breast ca • 3 month history of neck pain, able to flex rotate and extend the neck • Pain radiates to the right shoulder • Hand function intact • No myelopathy

  38. Treatment Options?

  39. Midthoracic Unknown primary Myelopathy: Sensory level T9 Babinski reflex MRI T9-T11 high-grade epidural spinal cord Compression No bone involvement No mechanical instability

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