Survival after Stereotactic Radiosurgery in the Era of Targeted Therapy: Number of Metastases No Longer Matters.

Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan-Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2-4 BMs (n = 438), 5-10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2-4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2-4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS.

The use of multiparametric 18F-fluoro-L-3,4-dihydroxy-phenylalanine PET/MRI in post-therapy assessment of patients with gliomas.

PURPOSE: To determine the utility of F-fluoro-L-3,4-dihydroxy-phenylalanine (F-DOPA) PET/MRI versus cross-sectional MRI alone in glioma response assessment and identify whether the two techniques demonstrate different tumour features. METHODS: F-DOPA PET/MRI studies from 40 patients were analysed. Quantitative PET parameters and conventional MRI features were recorded. Tumour volume was assessed on both PET and MRI. Using dynamic susceptibility contrast perfusion-weighted imaging, maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) were obtained. Within volume of tumours of tumour features and normal-appearing white matter (NAWM) drawn on MRI, standardised uptake value (SUV)max, CBF and CBV were recorded. Presence of residual active tumour was assessed by qualitative visual assessment. Receiver operating characteristic analysis was performed univariately and on parameter combination to analyse ability to determine presence/absence of disease. Reference standard for presence of viable tissue was biopsy or clinical follow-up. RESULTS: Median SUVmax was 3.4 for low-grade glioma (LGG) and 3.3 for high-grade glioma (HGG). There was a significant correlation between PWI parameters and WHO grade (P < 0.001), but no correlation with SUVmax. Median F-DOPA volume was 8216.88 mm for HGG and 6284.94 mm for LGG; MRI volume was 6316.57 mm and 5931.55 mm, respectively. SUVmax analysis distinguished enhancing and nonenhancing components from necrosis and NAWM and demonstrated active disease in nonenhancing regions. Visually, the modalities were concordant in 37 patients. Combining the multiparametric PET/MRI approach with all available data-enhanced detection of the presence of tumour (area under the curve 0.99, P < 0.01). CONCLUSION: MRI and F-DOPA are complementary modalities for assessment of tumour burden. Matching F-DOPA and MRI in assessing residual tumour volume may better delineate the radiotherapy target volume.

The impact of route of diagnosis on survival in patients with glioblastoma.

INTRODUCTION: The standard of care for glioblastoma is maximal debulking surgery followed by chemo-radiotherapy (CRT). Published data show worse outcomes for patients who present with GBM as an emergency. This study investigates prognostic factors in a cohort of GBM patients treated with postoperative CRT, and compares outcomes in patients who present via emergency pathways with those who present through outpatient clinics. METHODS: Patients with GBM operated on between 1 April 2010 and 5 October 2015 and then treated with postoperative CRT were included in the study. Data were collected from electronic patient records and radiotherapy planning systems. Survival data were censored on 22 March 2016. Univariate and multivariate analyses of prognostic factors were performed. RESULTS: 104 patients were studied; mean age 51.6 years (range 19 to 70 years). Median overall survival (OS) was 16.5 months, with 68.2% and 37.8% alive at 12 and 24 months respectively. On multivariate analysis, improved OS was associated with ECOG Performance Status of 0 (vs ≥1; p = .012), patient age <60 years (vs ≥60 years; p < .001), and surgical debulking or macroscopic complete resection (vs biopsy; p < .001). Patients who presented through emergency medical pathways had worse survival (p = .005). CONCLUSION: This study supports published data that initial presentation through emergency pathways is associated with worse outcomes in GBM, even in patients who remain fit enough to receive post-operative CRT.

Craniospinal irradiation with concomitant and adjuvant temozolomide--a feasibility assessment of toxicity in patients with glioblastoma with a PNET component.

There is no standard treatment for glioblastoma with elements of PNET (GBM-PNET). Conventional treatment for glioblastoma is surgery followed by focal radiotherapy with concurrent temozolomide. Given the increased propensity for neuroaxial metastases seen with GBM-PNETs, craniospinal irradiation (CSI) with temozolomide (TMZ) could be a feasible treatment option but little is known regarding its toxicity. The clinical records of all patients treated at two UK neuro-oncology centres with concurrent CSI and TMZ were examined for details of surgery, radiotherapy, chemotherapy and toxicities related to the CSI-TMZ component of their treatment. Eight patients were treated with CSI-TMZ, the majority (6/8) for GBM-PNET. All patients completed radiotherapy to the craniospinal axis 35-40 Gy in 20-24 daily fractions with a focal boost to the tumour of 14-23.4 Gy in 8-13 daily fractions. Concurrent TMZ was administered at 75 mg/m(2) for seven of the cohort, with the other patient receiving 50 mg/m(2). The most commonly observed non-haematological toxicities were nausea and vomiting, with all patients experiencing at least grade 2 symptoms of either or both. All patients had at least grade 3 lymphopaenia. Two patients experience grade 4 neutropaenia and grade 3 thrombocytopaenia. Three of the eight patients required omission of TMZ for part of their chemoradiotherapy and 3/8 required hospital admission at some point during chemoradiotherapy. The addition of TMZ to CSI did not interrupt radiotherapy. Principal toxicities were neutropaenia, lymphopaenia, thrombocytopaenia, nausea and vomiting. Treatment with CSI-TMZ merits further investigation and may be suitable for patients with tumours at high-risk of metastatic spread throughout the CNS who have TMZ-sensitive pathologies.

Long-term efficacy of fractionated radiotherapy for benign meningiomas.

PURPOSE: To assess long term efficacy of fractionated stereotactic radiotherapy (fSRT) in the treatment of benign intracranial meningiomas. MATERIALS AND METHODS: Retrospective study of 222 patients with histologically confirmed (58%) and unverified presumed (42%) grade I intracranial meningioma treated with fSRT in a single institution to doses of 50-55Gy in 30-33 fractions. RESULTS: At a median follow-up of 43months (range 3-144) the 5 and 10years local control (LC) were 93% and 86%. Patients with tumors involving the optic nerve (42 patients) and patients with cavernous sinus/parasellar region meningiomas (78 patients) had 5 and 10years LC of 100%. The 5 and 10years survival probabilities were 93% and 84%. On multivariate analysis gender and tumor site were independent predictors of LC. Worsening of pre-existing cranial nerve deficit occurred in 8 (3.5%) and onset of new deficit in 1 (0.5%) patient. Two patients with optic nerve sheath meningioma (1%) developed radiation retinopathy. There were no cases of radiation necrosis or second brain tumors. CONCLUSION: fSRT achieves excellent medium and long term tumor control with minimal morbidity particularly in patients with benign meningiomas involving the parasellar region and the optic nerves and questions the role of other treatment modalities for tumors at these locations.

Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort.

BACKGROUND AND PURPOSE: To assess the efficacy of stereotactic ablative radiotherapy (SABR) for the treatment of non-small cell lung cancer (NSCLC) through a systematic review of all relevant publications from 2006 to the present compared to controls treated with surgery. In the absence of Grade I evidence, the objective outcome data should form the basis for planning future studies and commissioning SABR services. MATERIALS AND METHODS: Standard systematic review methodology extracting patient and disease characteristics, treatment and outcome data from published articles reporting patient data from populations of 20 or more Stage I NSCLC patients treated with SABR with a median follow up of minimum of 1 year. The individual outcome measures were corrected for stage and summary weighted outcome data were compared to outcome data from a large International Association for the Study of Lung Cancer (IASLC) cohort matched for stage of disease with survival as the principal endpoint and local control (local progression free survival - local PFS) as the secondary endpoint. RESULTS: Forty-five reports containing 3771 patients treated with SABR for NSCLC were identified that fulfilled the selection criteria; both survival and staging data were reported in 3171 patients. The 2 year survival of the 3201 patients with localized stage I NSCLC treated with SABR was 70% (95% CI: 67-72%) with a 2 year local control of 91% (95% CI: 90-93%). This was compared to a 68% (95% CI: 66-70) 2 year survival of 2038 stage I patients treated with surgery. There was no survival or local PFS difference with different radiotherapy technologies used for SABR. CONCLUSIONS: Systematic review of a large cohort of patients with stage I NSCLC treated with SABR suggests that survival outcome in the short and medium term is equivalent to surgery for this population of patients regardless of co-morbidity. As selection bias cannot be assessed from the published reports and treatment related morbidity data are limited, a direct comparison between the two treatment approaches should be a priority. In the meantime, SABR can be offered to stage I patients with NSCLC as an alternative to surgery.

Hypofractionated radical radiotherapy in elderly patients with medically inoperable stage I-II non-small-cell lung cancer.

We described the results of a hypofractionated regimen (HFRT) in a cohort of elderly patients (36 subjects) with stage I-II non-small-cell-lung cancer (NSCLC), tumor size> or =3 cm and ineligible for surgery. HFRT was delivered in 20 daily fractions of 3 Gy per fraction with a total dose of 60 Gy. The median PTV was 145 cm(3). The primary purpose of study was to estimate the local tumor control at 2 years as well as the modifications in the lung function parameters at 6 and 12 months. The local tumor control was 63.9% at 2 years. The incidence of distant recurrence rate at 2 years was 50%. The overall-survival (OS), the cause-specific-survival (CSS) and the disease-free-survival (DSF) at 2 years were 55.6, 57.1, and 38.9%, respectively. The median OS, CSS, and DFS was 25.4 (CI 95% 21.7-32.9), 26.7 (CI 95% 22.5-33.5) and 23.4 months (CI 95% 18.6-30.1), respectively. The two clinical parameters with a positive influence on OS were a KPS> or =90 (HR 1.16; p=0.013) and tumor size< or =4 cm (HR 0.763; p=0.011). No grade 3-4 acute toxicity was reported. No significant change in lung function parameters was measured at 6 and 12 months. For patients with larger or centrally located tumors as well as for subjects with lymph nodes involvement SBRT may be of limited valiance. Although the performances of our regimen were lower than the ones achieved by SBRT, our therapeutic option may offer a lower incidence of complications against a satisfactory local tumor control.

The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas.

OBJECTIVE: To assess the long-term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure. DESIGN: A retrospective longitudinal study. PATIENTS AND METHODS: Forty-seven patients with active acromegaly were treated with conventional RT between 1982 and 1994. All patients were first operated on and successively irradiated at a dose of 45-50 Gy in 25-28 fractions for persistent (n = 40) or recurrent (n = 7) disease. MEASUREMENTS: Long-term GH/IGF-I secretion and local tumour control were evaluated regularly, and possible side-effects were searched for systematically, especially in terms of secondary endocrine dysfunction. Biochemical cure of acromegaly was defined by glucose-suppressed plasma GH levels below 1 microg/l during an oral glucose tolerance test (OGTT) and normal age-corrected IGF-I values. RESULTS: The 5-, 10- and 15-year overall survival rates were 98%, 95% and 93%, respectively. Suppression of GH during OGTT was seen in 9% of patients at 2 years, 29% at 5 years, 52% at 10 years, and 77% at 15 years. Age-corrected IGF-I levels were normal in 8% of patients 2 years after RT, and this proportion increased to 23%, 42% and 61% after 5, 10 and 15 years, respectively. Normalization of GH/IGF-I mainly depended on pre-RT levels. Local tumour control was 95% at 5, 10 and 15 years after treatment. Late toxicity was mainly represented by progressive hypopituitarism, which was present in 33% of patients at baseline and increased to 57%, 78% and in 85% of patients at 5 10 and 15 years after RT, respectively. CONCLUSION: Conventional RT is effective in the long-term control of GH-secreting pituitary adenomas, although with a high prevalence of progressive hypopituitarism. At present, it remains a suitable option in acromegalic patients uncontrolled by surgery or medical therapy.