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Josh Yamada MD FRCPC Department of Radiation Oncology Memorial Sloan Kettering Cancer Center

Dose Prescription, Tolerances, Side Effects and Safety and Efficacy of SBRT of the Spine IAEA Singapore SBRT Symposium. Josh Yamada MD FRCPC Department of Radiation Oncology Memorial Sloan Kettering Cancer Center. Spinal Cord Radiation Injury.

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Josh Yamada MD FRCPC Department of Radiation Oncology Memorial Sloan Kettering Cancer Center

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  1. Dose Prescription, Tolerances, Side Effects and Safety and Efficacy of SBRT of the SpineIAEA Singapore SBRT Symposium Josh Yamada MD FRCPC Department of Radiation Oncology Memorial Sloan Kettering Cancer Center

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

  3. 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

  4. Spinal Cord Tolerance

  5. Background • Dose-volume tolerances of the spinal cord in spinal stereotactic radiosurgery (SRS) have been difficult to define • Complication rates required to be very low • Published reports of myelopathy do not account for the total number of patients treated at given dose-volume combinations

  6. Purpose • Report spinal cord toxicity from single fraction spinal SRS • Provide a comprehensive atlas of complication incidence to identify dose-volume predictors of spinal cord toxicity

  7. Materials and Methods • Prospective database of all patients treated with single fraction SRS between 2003-2010 • Retrospective review for spinal cord toxicity • No prior radiation to region allowed • Spinal Cord Toxicity • Clinical Myelitis • MRI spinal signal changes not attributable to tumor progression or other causes

  8. Materials and Methods • DVH atlases were created • Complication rates with 95% confidence limits • Probabilities that complication rates were < 1% for myelitis and < 10% for signal changes were determined as a function of dose and absolute volume.

  9. Results: Cohort Characteristics

  10. Spinal Cord Toxicity with Single Fraction Paraspinal SRS • One case of clinical myelitis (0.4%) • 5 cases of signal changes without clinical signs or symptoms of myelopathy (2.4%)

  11. Spinal Cord Toxicity with Single Fraction Paraspinal SRS • All myelitis or signal changes: • Maximum cord dose > 13.33 Gy • Minimum doses to the hottest: • 0.1 cc > 10.66 Gy • 0.2 cc > 10 Gy • 0.5 cc > 9 Gy • 1 cc > 8 Gy Statistics for treatments with DVHs passing below the locations (v,d), chosen just below the Myelitis DVH.

  12. 95% confidence limit on signal changes rate for DVHs passing above plot point

  13. Myelitis: Probability that True Complication Rate > 2%

  14. Cord Signal Changes: Probability that True Complication Rate > 5%

  15. Conclusions • High dose paraspinal SRS has a low rate of clinical apparent myelopathy (<1%) • Asymptomatic spinal cord signal changes are more common (2%) • The following dose limits minimize the potential for spinal cord toxicity after SRS • Maximum cord dose < 13.3 Gy • Minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc < 10.66, 10, 9, and 8 Gy respectively

  16. Future Directions • Pooled multi-institutional effort to overcome limitations • Single institution cohort with homogeneously treated population • Limited events

  17. Cord Myelopathy Dosimetry

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

  19. 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.

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

  21. Vertebral Body Fracture Risk • Vertebral body involvement is a significant risk for fracture (p=0.02) • Not found to be significant risk factors: • Obesity, posterior element involvement, local kyphosis, pre-exisiting endplate infraction or fracture, • XRT dose

  22. N = 114 patients • FU = 10.9 months (median) • Grade 2 N= 5, Grade 3 N= 1, grade 4 N= 1

  23. Progressive risk of vertebral body fractures post high dose IGRT 63 year old female with NSCLC acute onset of back pain post 2400cGy to T5 10-O6 3-O7 3-O7

  24. Methods • 71 treated sites in 62 consecutive patients with solid tumor spine metastases • 1800-2400 cGy single fraction IGRT • Serial MRI every 3-4 months • All images reviewed by same 3 spine surgeons and neuroradiologist • Primary outcome: New fracture or progression of exisiting fracture • Secondary outcomes: • ASIA score • VAS pain score, narcotic use

  25. Results • Fracture/progression noted in 27 sites (39%) • 65% lytic, 17% mixed, 18% sclerotic • Lytic lesions were 6.8 times more likely to fracture vs. mixed/sclerotic lesions (p<0.001)

  26. Lytic vs. Non Lytic

  27. Function and Symptoms • Fracture/progression not correlated with • BMI • XRT dose • ASIA score not impacted • Median VAS score in fracture patients 5 vs 2 in non fracture patients (p=0.051) • Fracture patients more likely to use narcotics (70% vs. 41% p = 0.005)

  28. Conclusions • A high risk of radiographic vertebral body fracture was found after high dose single fraction radiation • Dose not a significant predictor • Lytic lesions and greater tumor involvement were found to be risk factors • ASIA score not affected • Patients with fracture were found to report more pain and require more narcotics • High dose radiation may contribute to the development of vertebral body fracture • Currently investigating the role of prophylactic kyphoplasty in highest risk patients

  29. Materials & Methods • 204 consecutive spinal metastases abutting the esophagus in 182 patients were treated with single fraction paraspinal SRS at MSKCC between 2003-2010 • Esophageal toxicity scored with NCI CTCAE 4.0 • Atlases of complication incidences were generated • Clinical factors were correlated with toxicity

  30. Cohort Characteristics

  31. Esophageal Toxicity with Single Fraction Paraspinal SRS

  32. Patients with Grade ≥ 3 Toxicity

  33. Dosimetric and Volumetric Predictors of Grade ≥ 3 Esophageal Toxicity

  34. Atlas of Complication Incidence for Grade ≥ 3 Acute or Late Esophageal Toxicity

  35. Dose Response Model for Grade ≥ 3 Esophageal Toxicity p < 0.0006

  36. Clinical Risk Factors for Developing Grade ≥4 Esophageal Toxicity

  37. Grade IV Esophageal Fistula • 45 year old male • Oligometastatic RCC • Symptomatic T3 lesion • 2400 cGy • Cord Dmax < 14 Gy • Esophagus 15 Gy / 2 cc

  38. Grade IV Esophageal Fistula • 4 months: Grade 2 esophageal pain • 4.5 months: EGD • 3 cm non bleeding ulcer @ 22 cm • Cold forceps biopsy • 6 months: Worsening pain • Increased ulceration with superinfection • ¾ circumference with moderate stenosis • Dilation and cold forceps biopsy • 6.5 months: Acute development of TEF • Multiple repairs and stent procedures • 11 months: Expired from distant progression

  39. Conclusions • High dose, single fraction paraspinal SRS has a low rate of grade ≥ 3 esophageal toxicity • Careful attention to esophageal doses minimizes toxicity • MSKCC: 2.5 cc of esophagus ≤ 14 Gy • Radiation recall reactions and iatrogenic manipulation of the irradiated esophagus predispose for development of grade ≥ 4 toxicity

  40. Toxicity Summary • Spinal cord injury at current dose levels is extremely rare • Poor statistics because of limited events • Vertebral body injury is common after spine SBRT • Radiographic 40% • Symptomatic 15-20% • Esophageal injury is most common and very worrisome complication

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