Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature.

AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. MATERIALS AND METHODS: Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. RESULTS: Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10-6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. CONCLUSION: Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.

Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Does Dose to an Oral Mucosa Organ at Risk Predict the Duration of Grade 3 Mucositis after Intensity-modulated Radiotherapy for Oropharyngeal Cancer?

Various methods have been described to delineate the oral mucosa organ at risk (OAR). This study examined whether dosimetric parameters derived from four different OARs correlated to the duration of acute grade 3 mucositis (G3M) in patients with oropharyngeal carcinoma. In total, 66 patients were included in this study. The duration of CTCAE version 3 G3M and the duration of strong opiate use were prospectively recorded, together with six patient factors. In addition, for each OAR the following dose parameters were derived: mean dose, V55, V50, V45, V40 and V30. No statistically significant correlation of version 3 G3M or duration of strong opiate use was noted with the tested parameters. However, a trend towards significance between duration of strong opiate use and pre-treatment weight was observed (P=0.053), reaching statistical significance on subsequent linear regression. This study failed to show a relationship between dosimetric parameters derived from four oral mucosa OARs and the duration of CTCAE version 3 G3M or duration of opiate use, potentially suggesting serial rather than parallel radiobiological phenomena. The utility of CTCAE version 4 G3M as an end point requires further investigation given its potential relationship to pre-treatment weight.

WITHDRAWN: Does Dose to an Oral Mucosa Organ at Risk Predict the Duration of Grade 3 Mucositis after Intensity-modulated Radiotherapy for Oropharyngeal Cancer?

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Linear accelerator stereotactic radiosurgery for vestibular schwannomas: a UK series.

AIMS: To evaluate non-auditory toxicity and local control after linear accelerator stereotactic radiosurgery (SRS) for the treatment of vestibular schwannomas. MATERIALS AND METHODS: The institutional policy was to use SRS for radiologically progressing vestibular schwannomas. Case notes and plans were retrospectively reviewed for all patients undergoing SRS for vestibular schwannomas between September 2002 and June 2012. All patients were surgically immobilised using a BrainLab stereotactic head frame. The treatment plan was generated using BrainLab software (BrainScan 5.03). The aim was to deliver 12 Gy to the surface of the target with no margin. Patients with a minimum of 12 months of follow-up were included for toxicity and local control assessment. Radiological progression was defined as growth on imaging beyond 2 years of follow-up. Overall local control was defined in line with other series as absence of surgical salvage. RESULTS: Ninety-nine patients were identified. Two patients were lost to follow-up. After a median follow-up interval of 2.4 years, the actuarial radiological progression-free survival at 3 years was 100% and overall local control was also 100%. However, two patients progressed radiologically at 3.3 and 4.5 years, respectively. Twenty-one of 97 (22%) evaluable patients suffered trigeminal toxicity and this was persistent in 8/97 (8%). Two of 97 (2%) suffered long-term facial nerve toxicity (one with associated radiological progression causing hemi-facial spasm alone). One of 97 (1%) required intervention for obstructive hydrocephalus. No statistically significant dosimetric relationship could be shown to cause trigeminal or facial nerve toxicity. However, 7/8 patients with persistent trigeminal nerve toxicity had tumours in contact with the trigeminal nerve. CONCLUSIONS: SRS delivering 12 Gy using a linear accelerator leads to high local control rates, but only prospective evaluation will fully establish short-term toxicity. In this study, persistent trigeminal toxicity occurred almost exclusively in patients whose tumour was in contact with the trigeminal nerve.

Effect of the UK postcode lottery on survival of patients with metastatic renal cancer: an audit of outcomes in patients with metastatic renal cancer suitable for treatment with tyrosine kinase inhibitors.

AIMS: To determine whether primary care trusts' agreement or refusal to fund sorafenib or sunitinib affects outcomes for patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: This retrospective audit was conducted in a tertiary referral centre for urological cancer. Requests to prescribe drugs not approved by the National Institute for Health and Clinical Excellence are recorded on a trust database. We obtained details of all requests made for sunitinib and sorafenib for patients with renal cell carcinoma since licence in 2006. Outcome measures analysed were overall survival measured from the date of request for funding and hospital resource use as measured from Payment by Results data. Known prognostic factors and the patient's Index of Multiple Deprivation score were assessed at baseline as potential confounders of survival difference. RESULTS: Seventy-nine patients were identified. The groups were similar with respect to prognostic factors and Index of Multiple Deprivation scores. Thirty-seven and eight patients had funding approved for sunitinib and sorafenib, respectively; 21 and 13 were turned down. Seven patients who were denied funding received one or other of these drugs by self-funding treatment. Survival was longer for patients who received treatment with a drug for which they had applied for funding than for those who did not (hazards ratio 0.46; 95% confidence interval 0.21-1.01; chi(2)=3.80; 1 d.f.; P=0.05); the advantage was similar for patients receiving sunitinib (hazards ratio=0.49; 95% confidence interval 0.18-1.36; chi(2)=1.86; 1 d.f.; P=0.17) and sorafenib (hazard ratio=0.44; 95% confidence interval 0.11-1.69; chi(2)=1.58; 1 d.f.; P=0.21). Overall National Health Service resource use apart from funding for the renal cancer drugs was similar for both groups. CONCLUSIONS: Compared with patients receiving treatment, patients denied access to sunitinib and sorafenib had substantially worse survival outcomes, despite receiving treatment from the same clinical team. Access to the new drugs did not have an effect on overall use of National Health Service resources by funded patients. Modern treatments for advanced renal cancer should be available to all National Health Service patients with the disease.