Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy.

We analysed the long-term outcomes of patients with primary optic nerve sheath meningioma (ONSM) treated with stereotactic radiotherapy (SRT). 26 patients with primary ONSM were treated with SRT between 2004 and 2013 at a single institution. SRT was delivered with image guidance to a median dose of 50.4 Gy in 28 fractions. 4 patients had prior surgical debulking. At a median radiological follow-up of 68 months, the MRI based tumour control was 100%. Visual acuity improved in 10 (38.4%), remained stable in 10 (38.4%) and was reduced in 6 (23.1%) patients following treatment. Stable or improved vision post-treatment was seen in 92.3% of patients with good pre-treatment vision (best corrected visual acuity 6/18 or better), compared to only 61.5% of patients with poor pre-treatment vision (best corrected visual acuity 6/24 or worse). Overall, the treatment was well tolerated with no Grade 2 or greater acute toxicity. Minimal other ophthalmic complications were seen with only one patient developing late onset Grade 3 radiation retinopathy.

Fractionated Stereotactic Radiotherapy for Cavernous Venous Malformations of the Orbital Apex.

PURPOSE: The objective of this study was to investigate the efficacy and safety of fractionated stereotactic radiotherapy in the treatment of cavernous venous malformation of the orbital apex. METHODS: The authors reviewed a prospective database from a single center of patients with cavernous venous malformation of the orbital apex who had treatment with fractionated stereotactic radiotherapy. The authors compared the symptoms, visual function and the size of the tumor pre- and posttreatment as well as reviewed the treatment details and the incidence of complications. RESULTS: Six patients received treatment with fractionated stereotactic radiotherapy for cavernous venous malformation involving the orbital apex. The median age was 48 (range, 32-63), and 50% were female. Patients received a dose of 45 to 50.4 Gy in 1.8 to 2 Gy fractions. Median follow up was 33 months (range, 18-66 months). The average tumor volume reduction at posttreatment imaging after 12 months was 63%. All lesions reduced in size postradiotherapy and remained controlled for the duration of follow up. All patients who had proptosis or a visual field defect had an improvement in the symptoms posttreatment. There were no complications of the treatment. CONCLUSION: Fractionated stereotactic radiotherapy appears to be a safe and effective management option for cavernous venous malformation of the orbital apex and leads to a sustained reduction of the volume of the lesion with associated improvement in symptoms and visual function.

Post-operative stereotactic radiotherapy for the treatment of intracranial haemangiopericytoma: 'A Study of Dose and Outcome'.

INTRODUCTION: This study was performed to assess the relationship between tumour response and radiation dose in equivalent 2 Gy per fraction (EQD2). METHOD: A retrospective cohort analysis of 21 patients with a diagnosis of intracranial haemangiopericytoma between 2000 and 2013 was included in this study. A total of 39 lesions were analysed. The equivalent dose in 2 Gy per fraction was calculated by assigning an alpha-beta ratio of 12 Gy. A paired t-test compared dose (EQD2) and tumour response, and as the outcome was binary, a logistic regression analysis was performed. RESULTS: In total, there were 14 cases of progression and 25 cases of non-progression. It was estimated that for a one unit increase in EQD2, the odds of non-progression were increased by a factor of 1.13 (P = 0.026). After adjusting for PTV volume, the estimated effect of EQD2 (min) on tumour response was stronger, with an estimated odds ratio of 1.36 for an increase of one unit and an odds ratio of 21.6 for an increase of 10 units (P = 0.015). The dose range varied with varying PTV volumes. Based on the logistic model, the probability of having non-progression is larger than 50% for EQ2Dmin doses larger than 30-40 Gy, in particular for volumes larger than 3.67 cm3 . CONCLUSION: This study demonstrates that there is a relationship between dose (EQD2) and outcome. With increasing dose, the likelihood of regression is higher. When adjusted for PTV volume, the response appeared stronger. The dose varied significantly with changes in the size of the PTV.

Recurrent glioblastoma: Current patterns of care in an Australian population.

This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, p<0.0001). All patients progressed after treatment for first progression with 43 patients (45%) receiving treatment at second progression. To our knowledge this is the first population-based pattern of care survey of treatment for rGBM in an era where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy.

Management of glioblastoma in Victoria, Australia (2006-2008).

We describe the management of patients with newly diagnosed glioblastoma multiforme (GBM) in a population-based cohort and compare this to a previously studied cohort. We performed a retrospective cohort study of patients diagnosed with GBM from 2006-2008 in Victoria, Australia. Patients were identified from the population-based Victorian Cancer Registry and their treating doctors surveyed by questionnaire. Outcomes were then compared to a study of GBM patients who were diagnosed between 1998 and 2000 using an identical methodology. We reviewed 351 eligible patients. There were slightly more males (62%) and a minority had multifocal disease (13%). Total macroscopic resection, partial resection or biopsy only was performed in 32%, 37% and 24% of patients, respectively. The majority of patients were referred to a radiation oncologist and medical oncologist postoperatively. A total of 56% of patients were treated with postoperative radiotherapy with concurrent and sequential temozolomide and had a median survival of 14.4 months. This was significantly better than patients treated with postoperative radiotherapy alone in the current or earlier cohorts (2006-2008: median survival 6.2 months, p<0.0001 versus 1998-2000: 8.9 months, p<0.0001). This study demonstrates that postoperative chemoradiation has become the standard of care in this Victorian population with an associated improvement in median survival.

Hypofractionated stereotactic radiotherapy for benign intracranial tumours of the cavernous sinus.

We present our experience with hypofractionated stereotactic radiotherapy (HSRT) using 15 fractions to treat benign conditions of the cavernous sinus (CS) and emphasise the outcome in terms of cranial nerve (CN) function and toxicity for long term safety and efficacy. We performed a retrospective review of prospectively collected data on 112 patients with benign tumours of the CS treated with HSRT between 1 January 1998 and 31 December 2009. While all tumours involved the CS, a separate analysis was undertaken for meningiomas and pituitary adenomas. The median follow-up was 77 months (range: 2.3-177). Fifty-seven patients (51%) had a diagnosis of meningioma and 55 (49%) had pituitary adenomas. Prior to HSRT, 82 patients (73%) underwent microsurgery. The median tumour volume was 6.6 cm(3) for meningiomas and 3.4 cm(3) for pituitary adenomas (interquartile range: 2.8-7.9), and the mean prescribed dose was 38 Gy (range: 37.5-40.0) to the tumour margin, delivered in 15 fractions. After HSRT, 57% of all preexisting cranial neuropathies either resolved or improved and 38% remained stable, whereas 5% deteriorated. The diagnosis of meningioma was the only variable associated with recovery of cranial neuropathy (p<0.001). Permanent CN complications occurred in three patients (3%). The 5 and 10 year actuarial freedom from progression for patients with meningiomas was 98% and 93%, respectively, and for patients with pituitary adenomas this was 96% and 96%, respectively. We demonstrate low rates of CN morbidity after HSRT and the possibility of resolution or improvement in CN function for common histologies involving the CS.

Stereotactic radiosurgery for 318 brain metastases in a single Australian centre: the impact of histology and other factors.

While melanoma brain metastases (BM) are consistently associated with worse survival compared to other histologies, whether they correlate with worse local control (LC) following stereotactic radiosurgery (SRS) is not yet well-defined. In this study of prospectively and retrospectively collected data we investigated the impact of histology and other host, tumour and treatment factors on overall survival (OS) and LC. We analysed 162 patients and 318 BM lesions from various histologies treated with SRS between 2005 and 2011. We included patients who received SRS as first-line treatment, as well as patients who received SRS for residual or recurrent BM following prior surgery, whole brain radiotherapy (WBRT) or both. Median OS for the entire cohort was 8.4 months. Median OS for tumour histologies of melanoma, lung and breast cancer were 5.1, 12.2, and 14.7 months, respectively. On multivariate analysis, melanoma predicted for worse OS (hazard ratio [HR] 1.515, p = 0.003) together with performance status (HR 1.662, p < 0.001) and uncontrolled systemic disease (HR 1.755, p = 0.003). Melanoma histology was also negatively predictive for LC (HR 1.828, p = 0.021) together with increasing tumour size (HR 1.038, p = 0.017). Other factors, including the use of WBRT with SRS, the use of planning treatment volume margins, and prescription dose were not significantly predictive for OS and LC. We conclude melanoma histology also portends poorer LC in the SRS setting. While survival depends significantly on the systemic behaviour of the disease, treatment refinements to reduce local failure still merit exploration, especially in the era of targeted therapies.

Living longer with adult high-grade glioma: setting a research agenda for patients and their caregivers.

The long-term survival of patients with adult high-grade glioma (HGG) remains poor, but for those who do live longer functional status and neurocognitive ability may be influenced by residual or recurrent tumour, or treatment-related complications. The aim of this review was to examine the current literature regarding the quality of life and experience of patients living longer with adult HGG and their caregivers, with a view to understanding the burden of treatment on patient abilities and deficits over time. Medline, PsychINFO and CINAHL databases were searched for the core concept of HGG in combination with an aspect of quality of long-term survival. Key findings of the 12 included studies were identified and synthesised thematically. There is a paucity of dedicated studies which have investigated the experiences of this cohort. The strength of existing literature is limited by the systematic exclusion of the poorest functioning patients and the under-representation of caregiver perspectives. Discrepancies in how patients view their quality of life were highlighted, despite consistent findings of significant physical and functional impairment. This review confirmed the presence of important differences between patient and caregiver views regarding patient abilities following treatment. Caregiver burden was found to be high, due to multiple dynamic and relentless stressors. The true experience of patients living longer with adult HGG and their caregivers remains unclear, particularly for patients with poorer neurocognitive and functional outcomes. Further research is required to clarify and replicate findings, explore discrepancies between patient and caregiver views, and to specifically investigate how caregiver needs and experiences may evolve over time.

Stereotactic radiosurgery for brain and spine metastases.

Metastases to the brain and spine are common and difficult to treat. Stereotactic radiosurgery (SRS) is a non-invasive treatment option for some individuals, and may obviate the need for open surgery and/or whole brain radiotherapy. Over the past decade there has been an increased number of patients undergoing SRS for the treatment of metastatic disease, and multiple published studies show favourable results in terms of local disease control. We review the available literature pertaining to the application of SRS for the treatment of brain and spine metastases, together with its limitations and outcomes.

Neuropsychological outcomes of stereotactic radiotherapy for cerebral arteriovenous malformations.

To our knowledge, this is the first study to investigate cognitive outcome in patients with large or surgically inaccessible cerebral arteriovenous malformations (AVMs), who were treated with hypo-fractionated stereotactic radiotherapy (HSRT). A sample of 10 patients with AVMs was assessed up to 3.5 years post-HSRT. All patients were treated with HSRT to a total dose of 55 Gy in 11 fractions over a treatment period of 2.5 weeks. Neuropsychological assessments were given prior to radiotherapy and then at three time points following radiotherapy: 6 weeks, 6 months and 2.5-3.5 years post-treatment. The cognitive domains of attention, processing speed, learning, memory, semantic processing, naming, verbal fluency, visuospatial and executive function were assessed. Findings revealed that prior to radiotherapy the patient group was impaired in five of the nine cognitive domains. Post-treatment performances remained stable in the majority of domains; however, there was some fluctuation in semantic processing and memory performances. At 6 weeks post-treatment, a mild decrement was found in semantic processing ability; however, restoration to baseline levels was observed from 6 months onwards. At 2.5-3.5 years post-treatment, improvement was seen in the cohort's ability to remember new information when performances were compared with earlier time points. This study demonstrated improvements in memory several years after HSRT treatment. Further, this form of treatment was not associated with long-term, harmful cognitive side effects for these 10 patients encouraging further study of this treatment method. Further evaluation of the entire cohort is required to assess efficacy in terms of AVM obliteration and other potential side effects.

Surgical treatment of poorly visualised and complex cerebrovascular lesions using pre-operative angiographic data as angiographic DynaCT datasets for frameless stereotactic navigation.

BACKGROUND: Digital subtraction angiography (DSA) is the "gold standard" for the imaging of cerebrovascular lesions, particularly cerebral aneurysms and arteriovenous malformations (AVMs). Current stereotactic navigation is based on computed tomography (CT) and magnetic resonance (MR) images, which-even despite the use of CT angiographic (CTA) or MR angiographic (MRA) sequences-may not reveal small lesions, and may not demonstrate all the different facets of complex lesions. OBJECTIVE: To develop frameless stereotactic protocols based on pre-operative cerebral angiograms for enhancing precision in intra-operative navigation and improve patient outcomes. METHODS: Pre-operative angiograms were obtained for ten patients requiring surgery for complex and/or poorly visualised cerebrovascular lesions. The angiographic data were captured as an angiographic DynaCT dataset and fused to pre-operative CT or MR imaging stereotactic sequences for pre-operative planning and intra-operative navigation. The utility of the angiographic DynaCT datasets for surgical navigation and treatment were assessed by the treating neurosurgeon. RESULTS: This technique enabled precise navigation and better treatment of cerebrovascular lesions that were either inadequately imaged or invisible to conventional pre-operative CT and/or MR imaging techniques. We found that its use in the surgical excision of a micro-AVM to be far superior to CTA and MRA datasets. Its use in seven cases was found to be superior to CTA and MRA datasets, and as useful as CTA or MRA datasets in two cases. CONCLUSION: Pre-operative formal cerebral angiography as an angiographic DynaCT dataset can be used safely and effectively for intra-operative navigation and treatment of cerebrovascular lesions, in particular, micro-cerebral AVMs.

Quality of life among acoustic neuroma patients managed by microsurgery, radiation, or observation.

OBJECTIVE: The main aim of this study was to examine differences in quality of life (QoL) among acoustic neuroma patients across the management options of microsurgery, radiation, and observation. Additional aims were to describe QoL and investigate management, medical, and demographic factors that predicted QoL in this patient group. STUDY DESIGN: Cross-sectional design, using a postal questionnaire. SETTING: Tertiary referral centers. PATIENTS: Participants included 180 adults diagnosed with, or treated for, a unilateral acoustic neuroma within 5 years of questionnaire distribution. The mean age of participants was 56.5 years, and 107 (59.4%) were female. INTERVENTION(S): Patients' acoustic neuromas were managed with microsurgery, radiation, or observation. MAIN OUTCOME MEASURE(S): Current QoL was measured using the Short Form 12 Version 2 (SF-12), and postmanagement changes in QoL were assessed with the Glasgow Benefit Inventory (GBI). RESULTS: No significant differences in SF-12 scores were found across microsurgery, radiation, and observation patients. However, microsurgery patients reported more deterioration on the GBI general well-being subscale than radiation patients and more improvement in the GBI social support scale than observation patients. Number of symptoms was a consistent predictor of SF-12 and GBI scores. CONCLUSION: This is only the second study to use multivariate statistical techniques and a large sample to examine QoL across the acoustic neuroma management options of microsurgery, radiation, and observation. There were few differences in QoL outcomes across management groups. Number of symptoms was an important factor in current QoL and postmanagement changes in QoL.

A qualitative exploration of quality of life among individuals diagnosed with an acoustic neuroma.

OBJECTIVES: To explore quality of life outcomes and the factors that influenced adjustment among individuals diagnosed with an acoustic neuroma. DESIGN: This qualitative study involved a focus group design. METHODS: Twenty-one participants who had been diagnosed with and/or treated for an acoustic neuroma since 2000 attended one of four focus groups. Transcripts of the focus group discussions underwent thematic analysis to explore and describe the quality of life of participants and factors that impacted on their adjustment to the condition. RESULTS: Important themes that emerged were 'physical symptoms', 'psychological wellbeing', 'social wellbeing', 'functional status', and 'psychosocial factors that influenced adjustment'. Factors that influenced adjustment included severity of physical symptoms, co-morbid conditions, optimism, control, social comparison, and social support. CONCLUSIONS: Participants conveyed a diverse range of experiences in relation to quality of life. In addition to severity of physical symptoms, psychosocial factors also emerged as important influences on quality of life.

Role of hypofractionated stereotactic radiotherapy in treatment of skull base meningiomas.

The objective of this paper is to examine the efficacy and safety of hypofractionated stereotactic radiotherapy (SRT) in the treatment of skull base meningiomas. Thirty-eight patients were treated with a median prescribed dose of 37.5 Gy in 15 fractions to the 80% isodose. Median follow-up was 47 months. Ten males and 28 females of median age 55.5 years were followed. SRT was the primary treatment in 15 patients, adjuvant in 10 and given for recurrence in 14 patients. On clinical follow-up 27 patients are unchanged and in six their symptoms have resolved. One patient had symptomatic deterioration and four patients have developed new symptoms. No patients have radiological evidence of progression. Our data suggest that conventional hypofractionated radiotherapy schemes for benign CNS disease may be useful in conjunction with stereotactic techniques. Such schemes are attractive in terms of resource allocation and where tumour size or cranial nerve tolerance is of concern.

The use of chemotherapy in patients with gliomas: patterns of care in Victoria from 1998-2000.

Chemotherapy has an increasing role in the management of gliomas. In particular, chemotherapy provides survival and quality of life benefits in the setting of recurrent high-grade gliomas and in patients with newly diagnosed glioblastoma multiforme. We have previously reported details on patterns of care regarding 828 patients diagnosed with a glioma in the state of Victoria for the period 1998-2000. We observed that 250 patients (30%) received chemotherapy at some stage of their illness, including neo-adjuvant, adjuvant and recurrent clinical settings. There was significant variation in the agents used and their scheduling. Chemotherapy was given at any time in only 15% of patients aged over 60 years. Eight percent of patients were enrolled on a chemotherapy clinical trial. As chemotherapy for gliomas becomes entrenched as the standard of care, this survey will provide an insight into changing patterns of care for the future and points to areas of need in management of these tumours.

Brain stem gliomas: patterns of care in Victoria from 1998-2000.

This study describes the management of and outcomes for adult and paediatric patients with newly diagnosed brain stem gliomas during 1998-2000 in Victoria. Adult patients were identified in a retrospective cohort study conducted by surveying doctors involved in managing incident brainstem glioma cases identified from the population-based Victorian Cancer Registry. Paediatric cases were identified from a retrospective analysis of the Victorian Paediatric Brain tumour database for the same period. Ten adult and 14 paediatric patients were considered eligible for this study. Nine (38%) did not have a histologic diagnosis but were diagnosed on the basis of radiological appearance. Complete macroscopic resection was performed in two patients (8%). A variety of tumour types and grades were observed with surgery and radiotherapy the mainstays of therapy. No adult patients and only eight (57%) paediatric patients received chemotherapy. The median survivals for adult patients, paediatric patients with pontine lesions and paediatric patients with non-pontine lesions were: 57, 10 and 60+ months respectively.

Management of glioma in Victoria (1998-2000): retrospective cohort study.

OBJECTIVE: To describe the management of and outcomes in a population-based cohort of patients with newly diagnosed glioma. DESIGN, SETTING AND PATIENTS: Retrospective cohort study of patients with glioma newly diagnosed over the period 1998-2000 in Victoria. Patients were identified from the population-based Victorian Cancer Registry (VCR). Doctors involved in managing the patients were surveyed by a questionnaire sent out in 2003. The cohort was followed until the end of 2004 to obtain at least 4 years' follow-up data on all patients. MAIN OUTCOME MEASURES: Reported treatment, referral patterns and survival rates. RESULTS: Over the study period, 992 cases of glioma were identified; 828 completed surveys on eligible patients were obtained (response rate, 93%); 473 patients (57%) had glioblastoma multiforme (GBM); 105 patients (13%) diagnosed with "glioma" had had no histological confirmation. Complete macroscopic resection was performed in 209 patients (25%); 612 patients (74%) were referred for radiotherapy and 326 (54%) for chemotherapy; 39 (5%) were enrolled on a clinical trial. Median survival was 9.2 months for all patients and 7.4 months for patients with GBM. CONCLUSIONS: This is the largest reported glioma management survey in the world to date. Much of the patient demographics and approach to treatment were as expected and represent a reasonable "standard of care". However, there are some areas for improvement, including the absence of histological diagnosis in some patients, lack of multidisciplinary care, low clinical trial enrollment and poor use of ancillary services.

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PURPOSE: To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. METHODS AND MATERIALS: Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. RESULTS: Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). CONCLUSIONS: Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

Factors predicting for urinary morbidity following 125iodine transperineal prostate brachytherapy.

PURPOSE: To assess factors related to the risk of acute urinary retention and other morbidity indices in patients undergoing transperineal seed implantation of the prostate. MATERIALS AND METHODS: One hundred and seventy-three consecutive patients treated with (125)Iodine transperineal interstitial permanent prostate brachytherapy (TIPPB) were evaluated. Various demographic, pathological, symptomatic, urodynamic and dosimetric values were assessed in relation to the incidence of acute urinary retention as well as the International Prostate Symptom Score (IPSS) dynamics. Patients were routinely placed on alpha-blockade postimplant. Dosimetry was based on CT scan one month postimplant. RESULTS: Acute urinary retention developed in thirty-four patients (19.7%), at a median time of four days. Peak urinary flow rate was the only independent factor which varied significantly between those suffering retention and those not (median of 16 and 19.5 ml/s respectively, P=0.005). Median preimplant IPSS was 4.0, with a median peak of 16 at 3 months. Actuarial median time to return to baseline IPSS was at 15 months. The peak IPSS above preimplant levels was correlated significantly in multivariate analysis with the number of seeds implanted superior to the physician-nominated anatomical base level of the prostate (P<0.009), as well as lower preimplant IPSS values. CONCLUSIONS: In our series, preimplant urinary flow rate was the most important factor predictive of postimplant acute urinary retention. The patients' risk of having heightened IPSS change following implantation was correlated to a lower preimplant IPSS and an increased number of seeds implanted above the level of the prostatic base, possibly reflecting bladder base rather than urethral irritation in the development of acute urinary morbidity.