Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors.

PURPOSE: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. METHODS AND MATERIALS: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1, 2, and 3 cc of brain volume (D(0.5), D(1), D(2), D(3)) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. RESULTS: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 ± 5 Gy (RBE) for no toxicity to 74 ± 5 Gy (RBE) for Grade 1 and to 76 ± 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of ≥ 64 Gy (RBE) D(3), ≥ 68 Gy (RBE) D(2), ≥ 72 Gy (RBE) D(1), and ≥ 73 Gy (RBE) D(0.5), respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. CONCLUSIONS: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing an organ-at-risk maximally permissible dose for BP.

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.

Spot-scanning proton radiation therapy for recurrent, residual or untreated intracranial meningiomas.

BACKGROUND AND PURPOSE: To assess the safety and efficacy of spot scanning proton beam radiation therapy (PRT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: Sixteen patients with intracranial meningioma (histopathologically proven in 13/16 cases) were treated with PRT between July 1997 and July 2002. Eight patients had skull base lesions. Thirteen patients received PRT after surgery either as adjuvant therapy for incomplete resection (eight patients) or for recurrence (five patients). Three patients received radical PRT after presumptive diagnosis based on imaging. The median prescribed dose was 56 CGE (range, 52.2-64, CGE=proton Gy X 1.1) at 1.8-2.0 CGE (median, 2.0) per fraction. Gross tumor volume and planning target volume ranged from 0.8 to 87.6 cc (median, 17.5) and 4.6-208.1 cc (median 107.7), respectively. Late ophthalmologic and non-ophthalmologic toxicity was assessed using the Subjective, Objective, Management and Analytic scale (SOMA) of the Late Effects of Normal Tissue scoring system and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v3.0) grading system, respectively. The median follow-up time was 34.1 months (range, 6.5-67.8). RESULTS: Cumulative 3-year local control, progression-free survival and overall survival were 91.7, 91.7 and 92.7%, respectively. No patient died from recurrent meningioma. One patient progressed locally after PRT. Radiographic follow-up (median, 34 months) revealed an objective response in three patients and stable disease in 12 patients. Cumulative 3-year toxicity free survival was 76.2%. One patient presented with radiation induced optic neuropathy (SOMA Grade 3) and retinopathy (SOMA Grade 2) 8.8 and 30.4 months after treatment, respectively. These patients with ophthalmologic toxicity received doses higher than those allowed for the optic/ocular structures. Another patient developed a symptomatic brain necrosis (CTCAE Grade 4) 7.2 months after treatment. No radiation-induced hypothalamic/pituitary dysfunction was observed. CONCLUSIONS: Spot-scanning PRT is an effective treatment for patient with untreated, recurrent or incompletely resected intracranial meningiomas. It offers highly conformal irradiation for complex-shaped intracranial meningiomas, while delivering minimal non-target dose. Observed ophthalmologic toxicity is dose-related.