Alessandra Bolsi

Treatment planning and verification of proton therapy using spot scanning: Initial experiences

Since the end of 1996, we have treated more than 160 patients at PSI using spot-scanned protons. The range of indications treated has been quite wide and includes, in the head region, base-of-skull sarcomas, low-grade gliomas, meningiomas, and para-nasal sinus tumors. In addition, we have treated bone sarcomas in the neck and trunk--mainly in the sacral area--as well as prostate cases and some soft tissue sarcomas. PTV volumes for our treated cases are in the range 20-4500 ml, indicating the flexibility of the spot scanning system for treating lesions of all types and sizes. The number of fields per applied plan ranges from between 1 and 4, with a mean of just under 3 beams per plan, and the number of fluence modulated Bragg peaks delivered per field has ranged from 200 to 45 000. With the current delivery rate of roughly 3000 Bragg peaks per minute, this translates into delivery times per field of between a few seconds to 20-25 min. Bragg peak weight analysis of these spots has shown that over all fields, only about 10% of delivered spots have a weight of more than 10% of the maximum in any given field, indicating that there is some scope for optimizing the number of spots delivered per field. Field specific dosimetry shows that these treatments can be delivered accurately and precisely to within +/-1 mm (1 SD) orthogonal to the field direction and to within 1.5 mm in range. With our current delivery system the mean widths of delivered pencil beams at the Bragg peak is about 8 mm (sigma) for all energies, indicating that this is an area where some improvements can be made. In addition, an analysis of the spot weights and energies of individual Bragg peaks shows a relatively broad spread of low and high weighted Bragg peaks over all energy steps, indicating that there is at best only a limited relationship between pencil beam weighting and depth of penetration. This latter observation may have some consequences when considering strategies for fast re-scanning on second generation scanning gantries.

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

PURPOSE To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. METHODS AND MATERIALS Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. RESULTS Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. CONCLUSIONS Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

A treatment planning comparison of 3D conformal therapy, intensity modulated photon therapy and proton therapy for treatment of advanced head and neck tumours

BACKGROUND AND PURPOSE In this work, the potential benefits and limitations of different treatment techniques, based on mixed photon-electron beams, 3D conformal therapy, intensity modulated photons (IM) and protons (passively scattered and spot scanned), have been assessed using comparative treatment planning methods in a cohort of patients presenting with advanced head and neck tumours. MATERIAL AND METHODS Plans for five patients were computed for all modalities using CT scans to delineate target volume (PTV) and organs at risk (OAR) and to predict dose distributions. The prescribed dose to the PTV was 54 Gy, whilst the spinal cord was constrained to a maximum dose of 40.5 Gy for all techniques. Dose volume histograms were used for physical and biological evaluation, which included equivalent uniform dose (EUD) calculations. RESULTS Excluding the mixed photon-electron technique, PTV coverage was within the defined limits for all techniques, with protons providing significantly improved dose homogeneity, resulting in correspondingly higher EUD results. For the spinal cord, protons also provided the best sparing with maximum doses as low as 17 Gy. Whilst the IM plans were demonstrated to be significantly superior to non-modulated photon plans, they were found to be inferior to protons for both criteria. A similar result was found for the parotid glands. Although they are partially included in the treated volume there is a clear indication that protons, and to a lesser extent IM photons, could play an important role in preserving organ functionality with a consequent improvement of the patients quality of life. CONCLUSIONS For advanced head and neck tumours, we have demonstrated that the use of IM photons or protons both have the potential to reduce the possibility of spinal cord toxicity. In addition, a substantial reduction of dose to the parotid glands through the use of protons enhances the interest for such a treatment modality in cases of advanced head and neck tumours. However, in terms of target coverage, the use of 3D conformal therapy, although somewhat inferior in quality to protons or IM photons, has been shown to be a reasonable alternative to the more advanced techniques. In contrast, the conventional technique of mixed photon and electron fields has been shown to be inferior to all other techniques for both target coverage and OAR involvement.

Spot-scanning-based proton therapy for extracranial chordoma.

PURPOSE To evaluate effectiveness and safety of spot-scanning-based proton-radiotherapy (PT) for extracranial chordomas (ECC). METHODS AND MATERIAL Between 1999-2006, 40 patients with chordoma of C-, T-, and L-spine and sacrum were treated at Paul Scherrer Institute (PSI) with PT using spot-scanning. Median patient age was 58 years (range, 10-81 years); 63% were male, and 36% were female. Nineteen patients (47%) had gross residual disease (mean 69 cc; range, 13-495 cc) before PT, and 21 patients (53%) had undergone prior titanium-based surgical stabilization (SS) and reconstruction of the axial skeleton. Proton doses were expressed as Gy(RBE). A conversion factor of 1.1 was used to account for higher relative biological effectiveness (RBE) of protons compared with photons. Mean total dose was 72.5 Gy(RBE) [range, 59.4-75.2 Gy(RBE)] delivered at 1.8-2.0 Gy(RBE) dose per fraction. Median follow-up time was 43 months. RESULTS In 19 patients without surgical stabilization, actuarial local control (LC) rate at 5 years was 100%. LC for patients with gross residual disease but without surgical stabilization was also 100% at 5 years. In contrast, 12 failures occurred in 21 patients with SS, yielding a significantly decreased 5-year LC rate of 30% (p = 0.0003). For the entire cohort, 5-year LC rates were 62%, disease-free survival rates were 57%, and overall survival rates were 80%. Rates were 100% for patients without SS. No other factor, including dosimetric parameters (V95, V80) were predictive for tumor control on univariate analysis. CONCLUSION Spot-scanning-based PT at PSI delivered subsequently to function-preserving surgery for tumor debulking, decompression of spinal cord, or biopsy only is safe and highly effective in patients with ECC without major surgical instrumentation even in view of large, unresectable disease.

Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute.

PURPOSE To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. METHODS AND MATERIALS Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. RESULTS Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. CONCLUSIONS Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.

Spot Scanning-Based Proton Therapy for Intracranial Meningioma: Long-Term Results From the Paul Scherrer Institute

BACKGROUND To assess the long-term clinical results of spot scanning proton therapy (PT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS Thirty-nine patients with meningioma (histologically proven 34/39) were treated with PT between July 1997 and January 2010. Thirty-two (82.1%) patients were treated as primary treatment (exclusive PT, n = 8; postoperative PT, n = 24). Mean age was 48.3 ± 17.9 years and 32 (82.1%) patients had skull base lesions. For patients undergoing surgery, 24 patients had a diagnosis of World Health Organization (WHO) Grade I and 10 of a WHO Grade II/III meningioma, respectively. The female-to-male ratio was 3.3. The median administered dose was 56.0 Gy (relative biologic effectiveness [RBE]) (range, 52.2-66.6) at 1.8-2.0 Gy (RBE) per fraction. Gross tumor volume (GTV) ranged from 0.76 to 546.5 cm(3) (median, 21.5). Late toxicity was assessed according to Common Terminology Criteria for Adverse Events version 3.0. Mean follow-up time was 62.0 months and all patients were followed for >6 months. RESULTS Six patients presented with tumor recurrence and 6 patients died during follow-up, of which 4 of tumor progression. Five-year actuarial local control and overall survival rates were 84.8% and 81.8%, respectively, for the entire cohort and 100% for benign histology. Cumulative 5-year Grade ≥3 late toxicity-free survival was 84.5%. On univariate analysis, LC was negatively influenced by WHO grade (p = 0.001), GTV (p = 0.013), and male gender (p = 0.058). CONCLUSIONS PT is a safe and effective treatment for patients with untreated, recurrent, or incompletely resected intracranial meningiomas. WHO grade and tumor volume was an adverse prognostic factor for local control.

Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy

PURPOSE To evaluate the long term tumor control and toxicity of skull base tumors treated with pencil beam scanning proton therapy (PT). MATERIALS AND METHODS PT was delivered to 151 (68%) and 71 (32%) chordoma and chondrosarcoma (ChSa) patients, respectively. Mean age of patients was 40.8±18.4years and the male to female ratio was 0.53. The postoperative tumor was abutting the brainstem or optic apparatus in 71 (32.0%) patients. The postoperative mean gross tumor volume (GTV) was 35.7±29.1cm(3). The delivered mean PT dose was 72.5±2.2GyRBE. RESULTS After a mean follow-up of 50 (range, 4-176) months, 35 local (15.8%) failures were observed between 10.9 and 85.4months. The estimated 7-year LC rate for chordoma (70.9%; CI95% 61.5-81.8) was significantly lower compared to the LC rate for ChSa patients (93.6%; 95%CI 87.8-99.9; P=0.014). The estimated 7-year distant metastasis-free- and overall survival rate was 91.6% (95%CI 91.6-98.6) and 81.7% (95%CI 74.7-89.5), respectively. On multivariate analysis, optic apparatus and/or brainstem compression, histology and GTV were independent prognostic factors for LC and OS. The 7-year high grade toxicity-free survival was 87.2 (95%CI 82.4-92.3). CONCLUSIONS PBS PT is an effective treatment for skull base tumors with acceptable late toxicity. Optic apparatus and/or brainstem compression, histology and GTV allow independent prediction of the risk of local failure and death in skull base tumor patients.

Novel Technique of Craniospinal Axis Proton Therapy with the Spot-Scanning System

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 minimized.Hintergrund und Ziel:Konventionelle Methoden der Bestrahlung der kraniospinalen Achse (CSI) sind kompliziert und beinhalten ein hohes Risiko für Spätfolgen. Dennoch bleibt die CSI für die Heilung einer Reihe von Hirntumoren im Kindesalter unerlässlich. In dieser Studie werden die Durchführbarkeit und potentielle Vorteile der Spot-Scanning-Protonentherapie geprüft.Material und Methodik:Ein 5,5-jähriger Junge mit Rezidiv eines Medulloblastoms sollte eine CSI erhalten und wurde am Paul Scherrer Institut mit einem einzigen dorsalen Feld am Spot-Scanning-System mit Protonen bestrahlt. Untersucht wurden die Dosisverteilung für Zielvolumina, Risikoorgane, Behandlungszeit, Reproduzierbarkeit der Lagerung, Nebenwirkungen (nach Kriterien der EORTC/RTOG) und Therapieergebnis.Ergebnisse:Mit dem Therapieplan konnte trotz der Verwendung nur eines Bestrahlungswinkels eine homogene Dosisverteilung für das Zielvolumen erreicht werden. Die applizierte Dosis an den ventral gelegenen Organen war vernachlässigbar. An Akuttoxizitäten wurden lediglich eine Grad-1-Reaktion der Haut und eine Grad-2-Reaktion am zentralen Nervensystem beobachtet. 2 Monate nach Abschluss der Behandlung trat eine vorübergehende Abgeschlagenheit auf. Nach 24-monatiger Beobachtungszeit ist der Junge weiterhin tumorfrei. Wachstums- und Schilddrüsenhormone sind herabgesetzt.Schlussfolgerung:Die Behandlung erwies sich bei dem beschriebenen Patienten als gut durchführbar und verträglich. Mit der Verwendung eines einzigen dorsalen Feldes konnten Probleme durch Feldanschlüsse vermieden werden, und die Dosis ventral des Zielgebiets wurde minimiert.

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 minimized.Hintergrund und Ziel:Konventionelle Methoden der Bestrahlung der kraniospinalen Achse (CSI) sind kompliziert und beinhalten ein hohes Risiko für Spätfolgen. Dennoch bleibt die CSI für die Heilung einer Reihe von Hirntumoren im Kindesalter unerlässlich. In dieser Studie werden die Durchführbarkeit und potentielle Vorteile der Spot-Scanning-Protonentherapie geprüft.Material und Methodik:Ein 5,5-jähriger Junge mit Rezidiv eines Medulloblastoms sollte eine CSI erhalten und wurde am Paul Scherrer Institut mit einem einzigen dorsalen Feld am Spot-Scanning-System mit Protonen bestrahlt. Untersucht wurden die Dosisverteilung für Zielvolumina, Risikoorgane, Behandlungszeit, Reproduzierbarkeit der Lagerung, Nebenwirkungen (nach Kriterien der EORTC/RTOG) und Therapieergebnis.Ergebnisse:Mit dem Therapieplan konnte trotz der Verwendung nur eines Bestrahlungswinkels eine homogene Dosisverteilung für das Zielvolumen erreicht werden. Die applizierte Dosis an den ventral gelegenen Organen war vernachlässigbar. An Akuttoxizitäten wurden lediglich eine Grad-1-Reaktion der Haut und eine Grad-2-Reaktion am zentralen Nervensystem beobachtet. 2 Monate nach Abschluss der Behandlung trat eine vorübergehende Abgeschlagenheit auf. Nach 24-monatiger Beobachtungszeit ist der Junge weiterhin tumorfrei. Wachstums- und Schilddrüsenhormone sind herabgesetzt.Schlussfolgerung:Die Behandlung erwies sich bei dem beschriebenen Patienten als gut durchführbar und verträglich. Mit der Verwendung eines einzigen dorsalen Feldes konnten Probleme durch Feldanschlüsse vermieden werden, und die Dosis ventral des Zielgebiets wurde minimiert.

Long-term outcomes and prognostic factors of skull-base chondrosarcoma patients treated with pencil-beam scanning proton therapy at the Paul Scherrer Institute.

BACKGROUND Skull-base chondrosarcoma (ChSa) is a rare disease, and the prognostication of this disease entity is ill defined. METHODS We assessed the long-term local control (LC) results, overall survival (OS), and prognostic factors of skull-base ChSa patients treated with pencil beam scanning proton therapy (PBS PT). Seventy-seven (male, 35; 46%) patients with histologically confirmed ChSa were treated at the Paul Scherrer Institute. Median age was 38.9 years (range, 10.2-70.0y). Median delivered dose was 70.0 GyRBE (range, 64.0-76.0 GyRBE). LC, OS, and toxicity-free survival (TFS) rates were calculated using the Kaplan Meier method. RESULTS After a mean follow-up of 69.2 months (range, 4.6-190.8 mo), 6 local (7.8%) failures were observed, 2 of which were late failures. Five (6.5%) patients died. The actuarial 8-year LC and OS were 89.7% and 93.5%, respectively. Tumor volume > 25 cm(3) (P = .02), brainstem/optic apparatus compression at the time of PT (P = .04) and age >30 years (P = .08) were associated with lower rates of LC. High-grade (≥3) radiation-induced toxicity was observed in 6 (7.8%) patients. The 8-year high-grade TFS was 90.8%. A higher rate of high-grade toxicity was observed for older patients (P = .073), those with larger tumor volume (P = .069), and those treated with 5 weekly fractions (P = .069). CONCLUSIONS This is the largest PT series reporting the outcome of patients with low-grade ChSa of the skull base treated with PBS only. Our data indicate that protons are both safe and effective. Tumor volume, brainstem/optic apparatus compression, and age were prognosticators of local failures.