Protons Added to Photon Radiation Improve Chordoma Control

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.