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Long Term Results of Proton Beam Radiotherapy for Clival Chordomas/Chondrosarcomas

Reporter: Abigail Berman Milby, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2012

Presenting Author/Institution: Yasutaka Hayashi, Ibaraki Prefectural Central Hospital, Japan

Background

• Tumors of the skull base often arise in the clivus. Common pathologies include chordomas, which are slow-growing, locally aggressive tumors of the bone that arise from embryonic remnants of the notochord, and chondrosarcomas, which are rare malignant cartilaginous tumors that account for 6% of skull base lesions.
• Treatment of both of these consists of surgical resection, which is rarely complete because of the complex anatomy from which they arise.
• Adjuvant radiation is recommended for chordomas and chondrosarcomas, as opposed to delayed radiation initiated at recurrence.
• Proton beam therapy is ideally suited to the treatment of the clival region as the distal fall-off of the Bragg peak permits sparing of many brain structures, including the visual apparatus, pituitary gland, temporal lobes, and brainstem.
• The goal of this treatment was to evaluate the efficacy of proton beam therapy (PBT) for patients with clival chordomas/chondrosarcomas

Methods

• Forty patients with clival chordomas/chondrosarcomas treated with proton beams with or without x-rays were retrospectively reviewed.
• Series 1 represents 18 patients who were treated by conventional fractionation at High Energy Accelerator Research Organization or Proton Medical Research Center (PMRC) in Tsukuba from 1989 to 2005.
• Median total tumor dose of 77.22 (69.26-104.5) cGy (RBE)
• There were 8 males and 10 females
• Average age 50 yo (14-74)
• Mixed proton/photon treatment was used with IMRT as the photon radiation
• Series 2 represents 22 patients treated by the hyperfractionation scheme (BID) at PMRC from 2006 to 2011.
• Median total tumor dose of 77.44 (60.4-78.5) cGy (RBE) in 1.4 cgy (RBE) fractions twice daily
• There were 9 males and 13 females
• Average age 48 (13-72)
• Median follow up time were 87.1 months (14-216.5) and 33.4 months (2.2-60.1) in series 1 and 2 respectively
• Proton RT was delivered using a passive scattering technique.

Results

• The authors present the data from two independent series:
• Series 1
• Local control at 4 years was 82.6%, at 5 years was 55.5%, at 10 years was 48.5%.
• Overall survival at 3 y was 83.3%, at 5 years was 66.7%, at 10 years was 43.8%.
• Local control and cause specific survival rates at 5 years directly after surgery were 73.3% and 81.8%, respectively, and were significantly longer than patients who received PBT at recurrence (statistically significant).
• 3/81 patients had radiation necrosis (2 grade 4, 1 grade 2)
• 2/18 had sarcomatous transformation
• Series 2:
• The dose prescribed was 77.44 Gy (RBE) in 64 fractions in 11 cases, of which there were 2 recurrences, and therefore, in 2008, the investigators increased the total dose to 78.4 Gy (RBE).
• Overall survival at 3 years was 91.7 % and local control at 3 years was 90.9% and at 5 years was 72.7%.
• No tumor-related deaths have been observed so far in this series.
• Observation median 33.4 months (2.2-60.1 months)
• In series 2, there have been no cases of radiation necrosis or sarcomatous transformation.

Author's Conclusions

• This is a detailed report of 40 cases of clival chordomas/chondrosarcomas treated with proton beam therapy.
• PBT immediately following surgery is favorable in patients with clival chordomas and chondrosarcomas in comparison to PBT at the time of recurrence.
• However, radiation necrosis and sarcomatous transformation occurred in this population, indicating that follow imaging is mandatory.
• PBT with hyperfractionation is now applied at the presenting institution to possibly decrease the risk of radiation necrosis while maintaining tumor control. A long term evaluation will be needed for further follow-up.

Scientific/Clinical Implications

• This is a detailed report of two treatment schemas for clival chordomas/chondrosarcomas, one with daily radiotherapy and one with twice daily radiotherapy. The authors conclude that twice daily radiotherapy is the superior technique, as this series demonstrated similar local control without radiation necrosis or sarcomatous transformation.
• It should be noted that the follow up time in the hyperfractionation series is shorter and therefore the late effects may not be fully realized. Nonetheless, radiobiologically, hyperfractionation should decrease the risk of late effects.
• Further follow up is required on the hyperfractionation arm.
• The authors discuss that there are no cases of sarcomatoid transformation (ST) in the hyperfractionation arm; however, whether the cases of ST are due to proton beam therapy remains unclear.
• The radiobiologic argument is often made for hypofractionation in the setting of sarcomas because of the potential for more lethal cell kill. The ideal study would randomize patients with clival chordomas/chondrosarcomas to daily radiotherapy, hyperfractionated, or hypofractionated arms.
• This paper highlights the need for immediate referral after surgery and frequent long-term imaging in this patient population.