Gudrun Goitein

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.

Intensity modulated proton therapy: A clinical example

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

A TREATMENT PLANNING INTER-COMPARISON OF PROTON AND INTENSITY MODULATED PHOTON RADIOTHERAPY

PURPOSE A comparative treatment planning study has been undertaken between standard photon delivery techniques,b intensity modulated photon methods and spot scanned protons in order to investigate the merits and limitations of each of these treatment approaches. METHODS Plans for each modality were performed using CT scans and planning information for nine patients with varying indications and lesion sites and the results have been analysed using a variety of dose and volume based parameters. RESULTS Over all cases, it is predicted that the use of protons could lead to a reduction of the total integral dose by a factor three compared to standard photon techniques and a factor two compared to IM photon plans. In addition, in all but one Organ at Risk (OAR) for one case, protons are predicted to reduce both mean OAR dose and the irradiated volume at the 50% mean target dose level compared to both photon methods. However, when considering the volume of an OAR irradiated to 70% or more of the target dose, little difference could be shown between proton and intensity modulated photon plans. On comparing the magnitude of dose hot spots in OARs resulting from the proton and IM photon plans, more variation was observed, and the ranking of the plans was then found to be case and OAR dependent. CONCLUSIONS The use of protons has been found to reduce the medium to low dose load (below about 70% of the target dose) to OARs and all non-target tissues compared to both standard and inversely planned photons, but that the use of intensity modulated photons can result in similar levels of high dose conformation to that afforded by protons. However, the introduction of inverse planning methods for protons is necessary before general conclusions on the relative efficacy of photons and protons can be drawn.

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.

The PSI Gantry 2: a second generation proton scanning gantry

PSI is still the only location in which proton therapy is applied using a dynamic beam scanning technique on a very compact gantry. Recently, this system is also being used for the application of intensity-modulated proton therapy (IMPT). This novel technical development and the success of the proton therapy project altogether have led PSI in Year 2000 to further expand the activities in this field by launching the project PROSCAN. The first step is the installation of a dedicated commercial superconducting cyclotron of a novel type. The second step is the development of a new gantry, Gantry 2. For Gantry 2 we have chosen an iso-centric compact gantry layout. The diameter of the gantry is limited to 7.5 m, less than in other gantry systems (approximately 10-12 m). The space in the treatment room is comfortably large, and the access on a fixed floor is possible any time around the patient table. Through the availability of a faster scanning system, it will be possible to treat the target volume repeatedly in the same session. For this purpose, the dynamic control of the beam intensity at the ion source and the dynamic variation of the beam energy will be used directly for the shaping of the dose.

Postoperative Proton Radiotherapy for Localized and Locoregional Breast Cancer: Potential for Clinically Relevant Improvements?

PURPOSE To study the potential reduction of dose to organs at risk (OARs) with intensity-modulated proton radiotherapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) photon radiotherapy for left-sided breast cancer patients. METHODS AND MATERIALS Comparative treatment-planning was performed using planning computed tomography scans of 20 left-sided breast cancer patients. For each patient, three increasingly complex locoregional volumes (planning target volumes [PTVs]) were defined: whole breast (WB) or chest wall (CW) = (PTV1), WB/CW plus medial-supraclavicular (MSC), lateral-supraclavicular (LSC), and level III axillary (AxIII) nodes = (PTV2) and WB/CW+MSC+LSC+AxIII plus internal mammary chain = (PTV3). For each patient, 3D-CRT, IMRT, and IMPT plans were optimized for PTV coverage. Dose to OARs was compared while maintaining target coverage. RESULTS All the techniques met the required PTV coverage except the 3D-CRT plans for PTV3-scenario. All 3D-CRT plans for PTV3 exceeded left-lung V20. IMPT vs. 3D-CRT: significant dose reductions were observed for all OARs using IMPT for all PTVs. IMPT vs. IMRT: For PTV2 and PTV3, low (V5) left lung and cardiac doses were reduced by a factor >2.5, and cardiac doses (V22.5) were by a factor of >20 lower with IMPT compared with IMRT. CONCLUSIONS When complex-target irradiation is needed, 3D-CRT often compromises the target coverage and increases the dose to OARs; IMRT can provide better results but will increase the integral dose. The benefit of IMPT is based on improved target coverage and reduction of low doses to OARs, potentially reducing the risk of late-toxicity. These results indicate a potential role of proton-radiotherapy for extended locoregional irradiation in left breast cancer.

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.

Initial experience of using an active beam delivery technique at PSI

SummaryAt PSI a new proton therapy facility has been assembled and commissioned. The major features of the facility are the spot scanning technique and the very compact gantry. The operation of the facility was started in 1997 and the feasibility of the spot scanning technique has been demonstrated in practice with patient treatments. In this report we discuss the usual initial difficulties encountered in the commissioning of a new technology, the very positive preliminary experience with the system and the optimistic expectations for the future. The long range goal of this project is to parallel the recent developments regarding inverse planning for photons with a similar advanced technology optimized for a proton beam.