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Randomized phase II trial of hypofractionated proton versus carbon ion radiation therapy in patients with sacrococcygeal chordoma-the ISAC trial protocol.

Uhl M, Edler L, Jensen AD, Habl G, Oelmann J, Röder F, Jäckel O, Debus J, Herfarth K - Radiat Oncol (2014)

Bottom Line: Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform.A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction.The aim of this study is to confirm the toxicity results of the Japanese data in raster scan technique and to compare it with the toxicity analysis of proton therapy given in the same fractionation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Matthias.Uhl@med.uni-heidelberg.de.

ABSTRACT

Background: Chordomas are relatively rare lesions of the bones. About 30% occur in the sacrococcygeal region. Surgical resection is still the standard treatment. Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform. A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction. The recurrence rate after surgery alone is comparatively high, such that adjuvant radiation therapy is very important for improving local control rates. Proton therapy is still the international standard in the treatment of chordomas. High-LET beams such as carbon ions theoretically offer biologic advantages in slow-growing tumors. Data of a Japanese study of patients with unresectable sacral chordoma showed comparable high control rates after hypofractionated carbon ion therapy only.

Methods and design: This clinical study is a prospective randomized, monocentric phase II trial. Patients with histologically confirmed sacrococcygeal chordoma will be randomized to either proton or carbon ion radiation therapy stratified regarding the clinical target volume. Target volume delineation will be carried out based on CT and MRI data. In each arm the PTV will receive 64 GyE in 16 fractions. The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points.

Discussion: The aim of this study is to confirm the toxicity results of the Japanese data in raster scan technique and to compare it with the toxicity analysis of proton therapy given in the same fractionation. Using this data, a further randomized phase III trial is planned, comparing hypofractionated proton and carbon ion irradiation.

Trial registration: ClinicalTrials.gov Identifier: NCT01811394.

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Related in: MedlinePlus

Dose distribution and DVH of a patient treated with 64GyE carbon ion therapy within the ISAC trial. a) dose distribution and b) dose volume histogram (DVH) of a patient within the trial.
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Figure 2: Dose distribution and DVH of a patient treated with 64GyE carbon ion therapy within the ISAC trial. a) dose distribution and b) dose volume histogram (DVH) of a patient within the trial.

Mentions: Rectum, bladder and bowel are defined as organs at risk. Rectum is defined therefore ranging from the anus to the recto sigmoid junction, the bowel as the remaining intestine in the pelvis without rectum. The maximum dose to the PTV-rectum is 57.6 GyE (90% isodose). The ED2 (2 Gy SD, α/β = 3.9 Gy) is 73.2 Gy. One third of the circumference should be below the 35% isodose (ED2: 20 Gy). The maximum dose for the other parts of the intestine is 51.2 GyE (80% isodose, ED2: 61.4 Gy). This dose may only appear in a small volume. The QUANTEC criteria for the rectum and the other parts of the intestine have to be observed (V50 < 50%, V60 < 35%, V65 < 25%, V70 < 20% and V75 < 15%) (Figure 2). The maximum dose to the cauda equina is 60 Gy (ED2).


Randomized phase II trial of hypofractionated proton versus carbon ion radiation therapy in patients with sacrococcygeal chordoma-the ISAC trial protocol.

Uhl M, Edler L, Jensen AD, Habl G, Oelmann J, Röder F, Jäckel O, Debus J, Herfarth K - Radiat Oncol (2014)

Dose distribution and DVH of a patient treated with 64GyE carbon ion therapy within the ISAC trial. a) dose distribution and b) dose volume histogram (DVH) of a patient within the trial.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016619&req=5

Figure 2: Dose distribution and DVH of a patient treated with 64GyE carbon ion therapy within the ISAC trial. a) dose distribution and b) dose volume histogram (DVH) of a patient within the trial.
Mentions: Rectum, bladder and bowel are defined as organs at risk. Rectum is defined therefore ranging from the anus to the recto sigmoid junction, the bowel as the remaining intestine in the pelvis without rectum. The maximum dose to the PTV-rectum is 57.6 GyE (90% isodose). The ED2 (2 Gy SD, α/β = 3.9 Gy) is 73.2 Gy. One third of the circumference should be below the 35% isodose (ED2: 20 Gy). The maximum dose for the other parts of the intestine is 51.2 GyE (80% isodose, ED2: 61.4 Gy). This dose may only appear in a small volume. The QUANTEC criteria for the rectum and the other parts of the intestine have to be observed (V50 < 50%, V60 < 35%, V65 < 25%, V70 < 20% and V75 < 15%) (Figure 2). The maximum dose to the cauda equina is 60 Gy (ED2).

Bottom Line: Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform.A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction.The aim of this study is to confirm the toxicity results of the Japanese data in raster scan technique and to compare it with the toxicity analysis of proton therapy given in the same fractionation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Matthias.Uhl@med.uni-heidelberg.de.

ABSTRACT

Background: Chordomas are relatively rare lesions of the bones. About 30% occur in the sacrococcygeal region. Surgical resection is still the standard treatment. Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform. A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction. The recurrence rate after surgery alone is comparatively high, such that adjuvant radiation therapy is very important for improving local control rates. Proton therapy is still the international standard in the treatment of chordomas. High-LET beams such as carbon ions theoretically offer biologic advantages in slow-growing tumors. Data of a Japanese study of patients with unresectable sacral chordoma showed comparable high control rates after hypofractionated carbon ion therapy only.

Methods and design: This clinical study is a prospective randomized, monocentric phase II trial. Patients with histologically confirmed sacrococcygeal chordoma will be randomized to either proton or carbon ion radiation therapy stratified regarding the clinical target volume. Target volume delineation will be carried out based on CT and MRI data. In each arm the PTV will receive 64 GyE in 16 fractions. The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points.

Discussion: The aim of this study is to confirm the toxicity results of the Japanese data in raster scan technique and to compare it with the toxicity analysis of proton therapy given in the same fractionation. Using this data, a further randomized phase III trial is planned, comparing hypofractionated proton and carbon ion irradiation.

Trial registration: ClinicalTrials.gov Identifier: NCT01811394.

Show MeSH
Related in: MedlinePlus