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

Abstract

BackgroundChordomas 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 designThis 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.DiscussionThe 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 registrationClinicalTrials.gov Identifier: NCT01811394.

Comparing the Use of Protons and Carbon Ions for Treatment

“…40 Retrospective data of 95 patients after hypofractionated carbon ion treatment at NIRS presented an overall survival rate and local control rate at 5 years of 86% and 88%, respectively. 43 41 Evaluating the toxicity after carbon ion treatment at NIRS, grades 3 and 4 toxicity mainly occurred in patients who received doses of 70 GyE or greater in 16 fractions.…”

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan

“…published the results of particle therapy using carbon ions or protons as a definitive treatment for primary sacral chordoma patients and reported that there were no significant differences between the two ion types. Although a randomized controlled trial is needed to validate this finding, a German group is conducting a phase II trial of PBT and carbon ion radiotherapy for chordomas of the SB, CSs of the SB, and sacrococcygeal chordomas …”

Radiobiological issues in prospective carbon ion therapy trials

“…CIRT at HIT continues in treating these indications within clinical trials and additionally established a number of clinical trial protocols for other tumor types. Since the beginning of clinical operation, a large number of single‐center clinical trials have been established at HIT and most of them are in the phase of recruiting patients . These trials may be separated into (a) trials testing a fully fractionated CIRT, (b) trials testing a photon treatment plus CIRT boost, and (c) trials testing CIRT with or without photon RT plus systemic therapy.…”