Debus, Jürgen

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures.

Introduction: Highly precise irradiation using carbon-12 (12C) ions is a new means for catheter-free ablation. Besides energy deposition leading to the dose distribution, nuclear interactions lead to by-product β+-activity that can be measured using positron-emission-tomography (PET). Hypothesis: In-beam PET scanning during focused myocardial irradiation using 12C can adequately depict 12C dose deposition. Methods: Pigs were irradiated with 25, 40, and 55 Gy for AV node (AVN), LA-PV junction, and local LV freewall ablations. PET measurement was performed by means of a double head camera system installed at irradiation site. Coincidences were captured in end-expiration during beam extraction pauses of the accelerator. Results: Evaluation of PET images was qualitatively performed using the coronal plane of the activity distribution superimposed on the contrast-CT in the center of the target contour. Strong β+-activities were measured in AVN and LV ablations. In AVN ablations, activity was localized to the target location, without target activity spreading to the level of the aortic root or coronary sinus (Figure A). Local LV irradiations revealed strong activity in the target location, slightly extending into left lung and chest wall (Figure B). In 55 Gy animals, the cardiac entry channel showed increased activity, decreasing in 40 Gy and more so in 25 Gy animals. Conclusion: This is the first study applying in-beam PET to track 12C dose-deposition into the target location for catheter-free ablation in intact animals. Correlation of β+-activity to electrophysiological outcome, lesion induction, and potential side-effects may be critically important in dosing therapy and predicting outcomes.

Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.