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Phase II Study of Proton Radiotherapy for Spine and Paraspinal Sarcoma



Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 9, 2006

Presenter: Thomas F. Delaney
Presenter's Affiliation: Massachusetts General Hospital, Boston, MA
Type of Session: Scientific

Background

  • Sarcomas located in the spinal axis have a poor prognosis, as local control of the disease is difficult to achieve:
    • obtaining clear surgical margins is challenging 
    • high radiation doses (>66 Gy) are desired, but photon therapy to this area is limited by the dose to critical neurologic structures (~50 Gy for the spinal cord)
  • Proton radiotherapy has better conformality than photon radiotherapy, as there is no exit dose, potentially allowing higher doses to be delivered to this area safely.
  • This study aimed to use proton radiotherapy to treat these tumors with the hope of improving local control without excessive toxicity.

Materials and Methods

  • Phase II, prospective, single-institution study
    • Criteria: non-metastatic, thoracolumbosacral spine/paraspinal sarcomas
    • Surgery: Maximal resection with either pre- or post-operative radiotherapy
    • Radiotherapy:
      • clinical target volume 1 (CTV1): 50.4 GyE at 1.8 Gy/fraction
      • based on patterns of local failure
      • could be given with photons; majority had ~30.6 with photons
      • pre-operatively if possible (19.8 for sacrococcygeal, 50.4 for thoracolumbar)
      • CTV2: original gross tumor or residual microscopic in tumor bed
    • Boost with proton radiotherapy to 70.2 GyE (or 61.2 for giant cell tumor or Ewing's sarcoma)
    • CTV3: residual gross disease after surgery: 77.4 GyE
    • dose reduction if given with chemotherapy or diabetes
    • 90-Y plaques were used on the dura intraoperatively when feasible
    • Chemotherapy: patients with high-grade tumors were treated with sequential adriamycin
  • Patients: 50 patients were treated between 12/1997 and 3/2005
    • Histology: 28 chordoma, 14 chondrosarcoma, 1 each of other histologies
    • 36 had primary tumors, 14 were recurrences
    • 11 thoracic, 13 lumbar, 26 sacral
    • 25 gross resections (17 with positive margins), 12 subtotal resections, and 13 were   biopsied only
    • Median size: 7 cm

Results

  • Median XRT dose: 76.6 GyE
  • 1 patient decided not to complete radiotherapy, but remainder completed radiotherapy
  • Median follow-up: 34 months
  • Local recurrences: 6/50 total
  • 4 isolated, 2 local + distant metastases
  • 4 chondrosarcomas/2 chordomas
  • 4 in patients treated for recurrence
  • Survival:
    • 4/50 tumor-related deaths, 2 unrelated, 1 lost to follow-up
  • Toxicity:
    • Acute Grade 3+: 1 sacral stress fraction (after 27 Gy and surgery)
    • Late Grade 3+:
      • - 2 sacral neuropathies
      • - 1 sacral fracture
      • - 1 rectal bleeding requiring transfusion
    • Grade 2 erectile dysfunction: 1 patient 

Author's Conclusions

  • High dose photon/proton XRT can be delivered to the spinal region for treatment of sarcomas.
  • Treatment-related morbidity to date appears acceptable.
  • These treatment results in such challenging tumors are very encouraging.
  • Will have to await additional follow-up, especially for the chordomas
  • Preferable to radiate at time of initial presentation
  • Potential concern about late sacral nerve toxicity in patients receiving 77.4 Gy

Clinical/Scientific Implications

  • The superior conformality of proton radiotherapy offers promise in the treatment of spine and paraspinal sarcomas, as it can achieve relatively high doses to the tumor and tumor bed, while sparing nearby critical structures.
  • The preliminary local failure rate (12% at 36 months median f/u) compares favorably to historical local failure rates of over 40%.
  • Longer follow-up will help define whether local control is maintained and whether there will be a late-toxicity benefit.  

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