Assessment of the α/ß ratios for arteriovenous malformations, meningiomas, acoustic neuromas, and the optic chiasma

Purpose: To determine alpha/beta (α/ß) values of arteriovenous malformations (AVM), meningiomas, acoustic neuromas (AN), and the optic chiasma using clinical data. Methods and materials:Data of dose/fractionation schedules form the literature, iso-effective for a specific clinical outcome, were analysed using the Fraction Equivalent plot (FE) method and the Tucker method. Established safe dose/fractionation schedules for the optic chiasma were used to determine its α/ß value. Results:With the FE plot method, an alpha/beta value of 3.76 Gray (Gy) (95 confidence level [CL]: 2.84.6 Gy) for meningiomas, 2.4 Gy (95 CL: 0.83.9 Gy) for acoustic neuroma, and 14.7 Gy (95 CL: 3.825.7 Gy) for arteriovenous malformations were determined. The respective alpha/beta values using the Tucker method were 3.3 Gy (95CL: 2.26.8 Gy), 1.77 Gy (95CL: 1.33.0 Gy) and-57 Gy (95CL:-79.6 to 35.2 Gy). No meaningful α/ß values could be determined for the optic chiasma. Conclusion:Acoustic neuromas with a low α/ß value would show no lesion intrinsic benefit from fractionation. Meningiomas probably benefit from a hypofractionated schedule. The high α/ß value for AVM can be explained but needs further research. Fractionation versus radiosurgery can be considered when the primary objective is to avoid normal tissue damage. © 2010 Informa UK Ltd.Articl

Long-term results of stereotactic proton beam radiotherapy for acoustic neuromas

Background and purpose: A retrospective study evaluating the role of hypofractionated stereotactic proton beam therapy for acoustic neuromas. Materials and methods: The data of 51 patients treated with hypofractionation (3 fractions) and followed up for a minimum of 2 years, were analyzed. Mean dose prescribed to ICRU reference point (isocenter) was 26 cobalt gray equivalent (CGyE) in 3 fractions. Mean minimum tumor dose was 21.4 CGyE/3. Cranial nerve functions were evaluated clinically. Serial MR Scans were used to evaluate local control. Results: With a mean clinical and radiological follow-up of 72 and 60 months respectively, the 5-year results showed a 98% local control, with a hearing preservation of 42%, a facial nerve preservation of 90.5% and a trigeminal nerve preservation of 93%. Conclusion: For those patients harboring large acoustic neuromas that are inoperable, hypofractionated stereotactic proton beam offers long-term control with minimal side-effects. © 2008 Elsevier Ireland Ltd. All rights reserved.Articl

Stereotactic proton beam therapy for intracranial arteriovenous malformations

Purpose: To investigate hypofractionated stereotactic proton therapy of predominantly large intracranial arteriovenous malformations (AVMs) by analyzing retrospectively the results from a cohort of patients. Methods and Materials: Since 1993, a total of 85 patients with vascular lesions have been treated. Of those, 64 patients fulfilled the criteria of having an arteriovenous malformation and sufficient follow-up. The AVMs were grouped by volume: <14 cc (26 patients) and <14 cc (38 patients). Treatment was delivered with a fixed horizontal 200 MeV proton beam under stereotactic conditions, using a stereophotogrammetric positioning system. The majority of patients were hypofractionated (2 or 3 fractions), and the proton doses are presented as single-fraction equivalent cobalt Gray equivalent doses (SFEcGyE). The overall mean minimum target volume dose was 17.37 SFEcGyE, ranging from 10.38-22.05 SFEcGyE. Results: Analysis by volume group showed obliteration in 67% for volumes <14 cc and 43% for volumes <14 cc. Grade IV acute complications were observed in 3% of patients. Transient delayed effects were seen in 15 patients (23%), becoming permanent in 3 patients. One patient also developed a cyst 8 years after therapy. Conclusions: Stereotactic proton beam therapy applied in a hypofractionated schedule allows for the safe treatment of large AVMs, with acceptable results. It is an alternative to other treatment strategies for large AVMs. AVMs are likely not static entities, but probably undergo vascular remodeling. Factors influencing angiogenesis could play a new role in a form of adjuvant therapy to improve on the radiosurgical results. © 2005 Elsevier Inc.Articl

Stereotactic proton beam therapy of skull base meningiomas

Purpose: To review outcomes for patients with skull base meningiomas treated using the stereotactic proton beam at the National Accelerator Center (NAC), Republic of South Africa. Methods and Materials: Since 1993, 27 patients with intracranial meningiomas have been treated stereotactically with protons at NAC. Of those, 23 were located on the skull base, were large or had complex shapes, and were treated with radical intent. Both stereotactic radiotherapy (SRT, 16 or more fractions) and hypofractionated stereotactic radiotherapy (HSRT, 3 fractions) were used. Eighteen patients underwent proton HSRT, while 5 patients were treated with SRT. The mean target volume for the HSRT group was 15.6 cm3 (range 2.6-63 cm3). The mean ICRU reference dose was 20.3 cobalt Gray equivalent (CGyE), and the mean minimum planning target dose was 16.3 CGyE. The mean clinical and radiologic follow-up periods were 40 and 31 months respectively. The mean volume in the SRT group was 43.7 cm3, with ICRU reference doses ranging from 54 CGyE in 27 fractions to 61.6 CGyE in 16 fractions. Results: In the HSRT group, 16/18 (89%) of patients remained clinically stable or improved, while 2/18 (11%) deteriorated. Radiologic control was achieved in 88% of patients, while 2 patients had a marginal failure. Among the 5 SRT patients, 2 were clinically better, and 3 remained stable. All SRT patients achieved radiologic control. Three patients (13%), 2 of them in the HSRT group, suffered permanent neurologic deficits. Analyzing different dose/fractionation schedules, an α/β value of 3.7 Gy for meningiomas is estimated. Conclusion: Proton irradiation is effective and safe in controlling large and complex-shaped skull base meningiomas. Copyright © 2001 Elsevier Science Inc.Articl

Relative biological efficiency of 192 MeV neutron radiation for the induction of chromosome aberrations in human lymphocytes of the peripheral blood.

The production of dicentric chromosomes in human lymphocytes by high-energy neutron radiation was studied at the neutron beam facility of iThemba Laboratory using a quasimonoenergetic 192 MeV neutron beam. The linear yield coefficient of the linear dose-response relationship for dicentric chromosomes was measured to be (0.096 &plusmn; 0.020) Gy-1. This confirms our earlier observations that the yield of dicentric chromosomes decreases with increasing neutron energy above 400 keV and is almost constant above 20 MeV. Using the linear-quadratic dose-response relationship for dicentric chromosomes established in blood of the same donor for 60Co g-rays as reference radiation, an average maximum low-dose RBE (RBEM) of 9 &plusmn; 3 for 192 MeV quasi-monoenergetic neutrons, with a dose-weighted average energy of 162.1 MeV, was obtained. The yield of chromosome aberrations due to neutrons from the low-energy breakup continuum of the quasi-monoenergetic neutron spectrum was determined by an additional measurement at a neutron emission angle of 16&deg; where the high-energy peak is strongly suppressed. Using this technique, a yield coefficient a = (0.121 &plusmn; 0.026) Gy-1 and an RBEM of 12 &plusmn; 4 for virtually monoenergtic 192 MeV neutrons was determined. The increased uncertainties result from the application of the (0&deg;-16&deg;) difference method

Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses

Purpose: This study aims at providing relative biological effectiveness (RBE) data under reference conditions accounting for the determination of the 'clinical RBE' of protons.Methods and Materials: RBE (ref. 60Co γ-rays) of the 200 MeV clinical proton beam produced at the National Accelerator Centre (South Africa) was determined for lung tolerance assessed by survival after selective irradiation of the thorax in mice. Irradiations were performed in 1, 3, or 10 fractions separated by 12 h. Proton irradiations were performed at the middle of a 7-cm spread out Bragg peak (SOBP). Control γ irradiations were randomized with proton irradiations and performed simultaneously. A total of 1008 mice was used, of which 96 were assessed for histopathology.Results: RBEs derived from LD50 ratios were found not to vary significantly with fractionation (corresponding dose range, ~2-20 Gy). They, however, tend to increase with time and reach (mean of the RBEs for 1, 3 and 10 fractions) 1.00, 1.08, 1.14, and 1.25 for LD50 at 180, 210, 240, and 270 days, respectively (confidence interval approximately 20%). α/β ratios for protons and γ are very similar and average 2.3 (0.6-4.8) for the different endpoints. Additional irradiations in 10 fractions at the end of the SOBP were found slightly more effective (~6%) than at the middle of the SOBP. A control experiment for intestinal crypt regeneration in mice was randomized with the lung experiment and yielded an RBE of 1.14 ± 0.03, i.e., the same value as obtained previously, which vouches for the reliability of the experimental procedure.Conclusion: There is no need to raise the clinical RBE of protons in consideration of the late tolerance of healthy tissues in the extent that RBE for lung tolerance was found not to vary with fractionation nor to differ significantly from those of the majority of early- and late-responding tissues. Copyright (C) 2000 Elsevier Science Inc.Articl