Long Term Follow-up After Charged Particle Therapy for Chordomas and Chondrosarcomas of the Head and Neck: the Lawrence Berkeley National Laboratory (LBNL) / University of California San Francisco (UCSF) Experience

Reviewer: Abigail Berman Milby, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 4, 2011

Presenting Author: K.K. Mishra
Presenter's Affiliation: University of California San Francisco, San Francisco, CA

Background

  • TheLawrence Berkeley National Laboratory (LBNL) performed helium and heavier charged particle radiotherapy jointly with MGH from 1975 to 1992. Unfortunately, follow-up ended in 1993 after the facility closed.
    • The first helium patient was treated in 1975, carbon and neon in 1977, argon in 1977, and silicon 1982.
    • This facility was the only facility in the United States and treated the most patients worldwide.
  • Heavy ion radiotherapy has a larger radiobiologic effect than photon radiation, and, combined with the possibility of a precise dose application, tumors can be irradiated with very high doses and minimal dose to organs-at-risk.
  • Chordomas and chondrosarcomas of the head and neck are usually located at the skull base and in close proximity to many radiosensitive organs-at-risk including the optic nerves and chiasm and brainstem.
  • Castro et. al (IJROBP, 1994)previously reported on the long-term follow up of 233 patients treated with charged particle radiotherapy to skull base tumors, showing excellent local control and survival outcomes.
  • This study reports the long-term clinical follow-up for LBNL-UCSF patients treated with charged particles for chordomas and chondrosarcomas of the head and neck.

Materials/Methods

  • From 1977 to 1992, 96 patients were irradiated with charged particles at the Lawrence Berkeley Laboratory for chordomas (64) and chondrosarcomas (32) of the head and neck.
    • There were 45 females and 51 males.
    • Median age at diagnosis was 40.5 years.
    • 82 patients were treated for primary tumors and 14 were treated for recurrent lesions and had been treated previously with surgery or radiotherapy.
  • Patients were treated with neon and/or helium and in some cases also with photons for tumors with a total planned dose of 60-80 GyE.
    • RBE values used were 1.3 for helium and 2.5 for neon (except for CNS, in which RBE was 1.6 and 4.5 respectively).

Results

  • Median follow-up was 7.4 years (8.8 years for chondrosarcomas and 7.2 years for chordomas).
  • 14 patients had greater than 20 years of follow-up.
    • 10 patients were alive and with no evidence of disease (range follow-up 20.7-31.7 years).
  • 34 of 96 patients were alive at last follow-up. Median follow-up for surviving patients was 9.9 years.
  • Overall survival (OS) by Kaplan-Meier method was 66.6%, 54.8%, 34.6%%, and 28.2% at 5, 10, 15, and 20 years.
    • 10-year OS for chondrosarcomas is 61.8% (13 of 32 surviving) and chordomas is 51.1% (21 of 64 surviving).

Author's Conclusions

  • This data demonstrates long-term survival in chordomas and chondrosarcomas in the head and neck treated with charged particle therapy.
    • Twenty (20)-year OS was 28.2%, indicating a large percent of patients were most likely cured.
  • This is the longest follow-up data available on patients treated with charged particle therapy heavier than protons.
  • The investigators are exploring further long-term local control, disease specific survival, and late normal tissue effects to better understand charged particle radiotherapy.

Clinical Implications

  • The authors have impressively collected long-term follow up on patients treated up to 32 years ago with charged particle radiotherapy. The large 20-year overall survival indicates that a significant subset of patients with chordoma or chondrosarcoma of the head and neck are cured of disease.
  • The long-term toxicities from charged particle radiotherapy will be an excellent addition to this study reporting survival outcomes.
  • Proton therapy has also great potential for the treatment of skull base chordomas and chondrosarcomas (Munzenrider and Liebsch, Strahlenther Onkol 1999). A comparative study of the survival and toxicities following proton vs. heavy charged particle radiotherapy would be an interesting addition to the existing body of literature.
  • There are international phase III trials underway investigating charged particle therapy for chordomas and chondrosarcomas (Pommier et al. Radiotherapy and Oncology 2010).

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