Protonentherapie mit "Spot-Scanning" bei Rhabdomyosarkomen im frühen Kindesalter: Erste Erfahrungen am PSI

Ziel:: Die Durchführbarkeit und Verträglichkeit der Spot-Scanning-Protonentherapie in tiefer Sedierung bei Kindern mit Rhabdomyosarkomen (RMS) sollten geprüft werden. Patienten und Methodik:: Seit 2004 werden junge Kinder am Paul Scherrer Institut (PSI), Villigen, Schweiz, auch in tiefer Sedierung mit Protonen bestrahlt. Ausgewertet wurden Kinder unter 5 Jahren mit RMS im Bereich des Kopfes und Körperstamms. Alle Kinder waren in eine Therapieoptimierungsstudie eingeschlossen und wurden prospektiv hinsichtlich der Verträglichkeit der Bestrahlung untersucht. Ergebnisse:: Neun Kinder im medianen Alter von 1,9 Jahren wurden untersucht (sechs embryonale RMS und je ein alveoläres, undifferenziertes und nicht klassifizierbares RMS). Die Lokalisationen waren parameningeal (n = 4), orbital (n = 3), Kopf-Hals-Bereich (n = 1) und Prostata (n = 1). Bei allen Kindern lag ein IRS-Stadium III vor. Die Bestrahlung erfolgte ausschließlich mit Protonen (Gesamtdosen 46-54 CGE [Cobalt-Gray-Äquivalent]). Akuttoxizitäten Grad 3 oder 4 nach RTOG/EORTC traten ausschließlich im Bereich des Knochenmarks auf. Schlussfolgerung:: Die Protonentherapie bei RMS im frühen Kindesalter war problemlos durchführbar und hervorragend verträglich. Prospektive, standardisierte Erhebungen von Spättoxizität und Lebensqualität sind essentiel

Novel Technique of Craniospinal Axis Proton Therapy with the Spot-Scanning System: Avoidance of Patching Multiple Fields and Optimized Ventral Dose Distribution

Background and Purpose:: Conventional craniospinal irradiation (CSI) is a complex procedure carrying a high risk of adverse side effects. Still, it is indispensable for cure in a number of pediatric brain tumors. In this study, the feasibility and the potential advantage of spot-scanning proton therapy for CSI are investigated. Material and Methods:: A boy (5.5 years of age) with a recurrent medulloblastoma received CSI with a single posterior field using the spot-scanning system at Paul Scherrer Institute. Dose distribution to the targets and the organs at risk, treatment time, reproducibility of patient positioning, toxicity (according to EORTC/RTOG score), and treatment outcome were evaluated. Results:: The plan achieved a homogeneous coverage of the target volume, even using a single field. The doses to the organs ventral to the target were minimized. During treatment, grade 1 skin reaction and grade 2 central nervous system toxicity were observed. After 2 months, the boy presented with a transitory fatigue. After 24 months, he is alive and free of disease. Growth hormones and thyroid hormones are reduced. Conclusion:: These results, based on a single patient, suggest that spot-scanning proton therapy for craniospinal treatment is feasible and safe. By applying a single dorsal field, difficulties of multiple-field patching can be avoided and the ventral dose spread can be minimize

Pencil beam scanning proton therapy for pediatric intracranial ependymoma

To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54-60) delivered in 1.8-2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts

Relative biologic effectiveness determination in mouse intestine for scanning proton beam at Paul Scherrer Institute, Switzerland. Influence of motion.

PURPOSE: To determine the relative biologic effectiveness (RBE) of the Paul Scherrer Institute (PSI) scanning proton beam in reference conditions and to evaluate the influence of intestine motion on the proton dose homogeneity. METHODS AND MATERIALS: First, RBE was determined for crypt regeneration in mice after irradiation in a single fraction. Irradiation was performed at the middle of a 7-cm spread out Bragg peak (SOBP; reference position), as well as in the proximal part of the plateau and at the distal end of the SOBP. Control gamma-irradiation was randomized with proton irradiation and performed simultaneously. Second, motion of mouse intestine was determined by radiographs after copper wire markers had been placed on the jejunum and intestinal wall. RESULTS: Proton RBE (reference (60)Co gamma) was equal to 1.16 for irradiation at the middle of the SOBP and to 1.11 and 1.21 for irradiation in the initial plateau and end of the SOBP, respectively. The confidence intervals for these RBE values were much larger than those obtained in the other proton beams we have tested so far. They exceeded +/-0.20 (compared with the usual value of +/-0.07), which resulted from the unusually large dispersion of the individual proton data. The instantaneous positions of the mice intestines varied by +/-2 mm in the course of irradiation. CONCLUSION: The results of this study have shown that the RBE of the PSI proton beam is in total accordance with the RBE obtained at the other centers. This experiment has corroborated that proton RBE at the middle of the SOBP is slightly larger than the generic value of 1.10 and that there is a slight tendency for the RBE to increase close to the end of the SOBP. Also, excessive dispersion of individual proton data may be considered to result from intestine motion, taking into account that irradiation at the PSI is delivered dynamically by scanning the target volume with a pencil proton beam ("spot scanning"). Because 2-mm movements resulted in significant variations in local dose depositions, this should be considered for moving targets. Strategies to reduce this effect for the spot scanning technique have been developed at the PSI for radiotherapy of humans

Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at paul scherrer institute

PURPOSE: To evaluate postoperative spot-scanning proton radiation therapy (PT) and intensity-modulated PT (IMPT) for chordoma and chondrosarcoma in pediatric patients. METHODS AND MATERIALS: Between 2000 and 2005, 10 patients (six male patients, four female patients; six chordomas, four chondrosarcomas), aged 10-20 years (median, 16 years), were treated at our institute. Tumor sites were in the brain (one case), skull base (five cases), cervical (three cases), and lumbar spine (one case). Three children had complete resections. In seven children, resection was incomplete, leaving residual tumor behind (range, 2.3-46.3 mL). PT was delivered using spot scanning, with (three patients) or without (seven patients) IMPT. Total dose was 74.0 cobalt Gray equivalents (CGE) for chordoma, and 63.2-68.0 CGE for chondrosarcoma (median, 66.0), depending on histopathological grading and whether the patient had concurrent chemotherapy. RESULTS: Median follow-up time was 36 months (range, 8-77 months). Radiation treatment was well tolerated. All patients remained failure-free at their last follow-up. Late adverse events were reported in three patients and were mild (neurosensory in one patient; alopecia and hypoaccusis in one patient) to moderate (one patient, Grade 2 pituitary insufficiency). CONCLUSIONS: Postoperative spot-scanning PT, delivered in combination with and without IMPT, for chordoma and chondrosarcoma in children and adolescents was tolerated without unacceptable adverse event and initial outcome is perfectly satisfactory in this small cohort. Longer follow-up time and larger cohort are needed to more fully assess tumor control, adverse events, as well as functional and cosmetic outcome