Spot scanning proton therapy in the curative treatment of adult patients with sarcoma: the Paul Scherrer institute experience.

PURPOSE: To assess the safety and efficacy of spot scanning proton beam therapy (PT) in the curative treatment of soft-tissue sarcoma (STS) in adults patients. PATIENTS AND METHODS: We identified 13 STS patients treated with PT between July 1998 and May 2005 in our institutional database. Tumor histology varied with the most common histologic subtypes including liposarcoma and peripheral nerve sheet tumor. All tumors were located in vicinity of critical structures, such as the spinal cord, optic apparatus, bowel, kidney, or bowel. Of the patients, 6 and 5 patients received PT either as adjuvant therapy for non-R0 resection or for recurrence, respectively. Two patients received radical PT for unresectable disease. The median prescribed dose was 69.4 CGE (CGE = proton Gy x 1.1)-Gy (range, 50.4-76.0) at 1.8 to 2 CGE-Gy (median, 1.9) per fraction. Pre-PT anthracycline-based chemotherapy was delivered to 3 patients only. No patient has been lost to follow-up (median 48.1 months, range, 19.1-100.7 months). RESULTS: Of the 13 patients, all but 2 patients were alive. Local recurrence developed in 3 (23%) patients. The administered dose to these patients was < or =60 Gy-CGE. Distant control was achieved in all but 2 patients (lung metastasis), 1 of whom presented with a concomitant local recurrence. The 4-year local control and metastasis-free survival rates were 74.1% and 84.6%, respectively. Late grade > or =2 toxicity was observed in only 2 patients. CONCLUSIONS: Spot scanning PT is an effective and safe treatment for patient with STS in critical locations. The observed toxicity rate was acceptable.

Extracranial chordoma: Outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation.

PURPOSE: To evaluate the use of postoperative proton therapy (PT) in extracranial chordoma. PATIENTS AND METHODS: Twenty-six patients were treated. Gross total resection was achieved in 18 patients. Nine patients had cervical, 2 had thoracic, 8 had lumbar, and 7 had sacro-coccygeal chordomas. Thirteen patients had implants. PT was administered after function-preserving surgery, using a gantry and spot scanning, without or with intensity modulation (IMPT; 6 patients), and/or photon-based radiotherapy (RT, 6 patients). Median total dose was 72 cobalt Gray equivalent (CGE; range, 59.4-74.4), with means of 70.5 and 73.2 CGE for patients with and without implants. Median follow-up time was 35 months (range, 13-73 months). Adverse events were scored using the Common Terminology Criteria for Adverse Events grading system (version 3.0). RESULTS: At 3 years, actuarial overall survival (OS) and progression-free survival (PFS) rates were 84% and 77%, respectively. One patient each died of local failure (LF), distant failure (DF), suicide, and secondary tumor. We observed 5 LFs and 3 DFs; 3-year LF-free and DF-free survival rates were 86%. We observed four radiation-induced late adverse events (Grade 2 sensory neuropathy; Grade 3 subcutaneous necrosis, and osteonecrosis; and Grade 5 secondary cancer). In univariate analysis, implants were associated with LF (p = 0.034). Gross residual tumor above 30 mL was negatively associated with OS (p = 0.013) and PFS (p = 0.025). CONCLUSIONS: Postoperative PT for extracranial chordomas delivered with spot scanning offers high local control rates. Toxicity was acceptable. Implants were significantly associated with LF. Residual tumor above 30 mL impacted negatively on OS and PFS.

Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute.

PURPOSE: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. METHODS AND MATERIALS: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). RESULTS: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. CONCLUSIONS: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed.

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.

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.