Long-Term Follow-up of Patients Treated at a Single Institution Using a Passively Scattered Proton Beam; Observations Around the Occurrence of Second Malignancies.

PURPOSE: To investigate the occurrence of second malignancies resulting from the secondary radiation from a passively scattered proton beam. METHODS AND MATERIALS: A cohort of patients with long-term follow-up was defined. All were treated at the same institution with the same proton delivery system, consisting of a 200 MeV fixed, horizontal, passively scattered beam combined with a robotic chair. This setup allows for stereotactic positioning and permits fractionated treatments. The majority of patients underwent cranial or intracranial stereotactic radiation therapy. Patients with previous photon therapy or a follow-up of 24 months or less were excluded. For out-of-field secondary malignancies (SMs), the observed incidence in the study population was compared to the risk of developing a malignancy in the general population, taking patient sex into account. RESULTS: From September 1993 to May 2016, a total of 524 patients received proton beam therapy, and 322 patients could be evaluated for this study (164 female and 158 male). Age ranged from 2 to 85 years, with a median of 40 years. Follow-up ranged from 25 to 276 months, with a median of 150 months (12.5 years). During the study observation period, 7 patients had out-of-field new malignant disease. Three female patients developed a malignancy, compared with an expected incidence of 4.09 (standardized incidence ratio, 0.73 [95% confidence interval, 0.24-2.27]); 4 male patients developed a malignancy, versus an expected incidence of 3.99 (standardized incidence ratio, 1.00 [95% confidence interval, 0.38-2.67]). New intracranial disease developed in 9 patients: 8 meningiomas and 1 carcinoma. CONCLUSIONS: For out-of-field SMs, no increased risk of developing a variety of malignancies was observed. For in-field SMs, only 1 malignant histology was noted 15 years after the original proton therapy. No SM was observed in children and young adults.

Evaluation of the potential of inducing neurocognitive changes in patients receiving intracranial stereotactic irradiation for benign tumors: a preliminary study.

OBJECTIVE: To fully evaluate the efficacy of intracranial stereotactic irradiation, tumour control needs to be assessed in conjunction with the effects of radiation on normal tissue and the potential for changes in physiology, cognition and quality of life. This prospective pilot study investigated whether intracranial stereotactic irradiation induces cognitive changes in patients with cranial and base of skull lesions that did not directly involve the brain parenchyma. The value of a software-based psychometric approach to neurocognitive testing was also examined. METHODS: Thirty-four patients were enrolled, with 23 having sufficient data for statistical analyses. Pre-treatment baseline composite test score results for memory, attention, motor, language, executive function, and social function were compared to post-radiotherapy scores at final evaluation (median follow-up 24 months, range 12-59 months). Testing was done using the Brain Resource Company® (BRC) Internet accessed cognitive function test batteries, namely the WebNeuro® and IntegNeuro®, and the BRISC® (Brain Resource Inventory for Social Cognition). RESULTS: Quantitative results revealed no overall decline in cognitive function, and improvement in both executive functioning (p = 0.0002) and social functioning (p = 0.0016). Qualitatively, 6 patients at the final endpoint, and 4 patients at 12 months, were found to have a decline in one or more domains of function; with some of the patients who declined also showing improvement in certain domains. CONCLUSION: Overall, no statistically significant evidence of cognitive decline was observed following intracranial stereotactic irradiation, at either 12 months or beyond.

Assessment of the alpha/beta ratios for arteriovenous malformations, meningiomas, acoustic neuromas, and the optic chiasma.

PURPOSE: To determine alpha/beta (alpha/beta) 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 alpha/beta value. RESULTS: With the FE plot method, an alpha/beta value of 3.76 Gray (Gy) (95% confidence level [CL]: 2.8-4.6 Gy) for meningiomas, 2.4 Gy (95% CL: 0.8-3.9 Gy) for acoustic neuroma, and 14.7 Gy (95% CL: 3.8-25.7 Gy) for arteriovenous malformations were determined. The respective alpha/beta values using the Tucker method were 3.3 Gy (95%CL: 2.2-6.8 Gy), 1.77 Gy (95%CL: 1.3-3.0 Gy) and -57 Gy (95%CL: -79.6 to -35.2 Gy). No meaningful alpha/beta values could be determined for the optic chiasma. CONCLUSION: Acoustic neuromas with a low alpha/beta value would show no lesion intrinsic benefit from fractionation. Meningiomas probably benefit from a hypofractionated schedule. The high alpha/beta 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.

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.

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 > or =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 > or =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.