Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma?

Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12-18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9-13.0 months) and 17 months (95 % CI 11.6-22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.     

Impact of timing of radiation therapy on outcomes in atypical meningioma: A clinical audit

Background

The role of early adjuvant radiation therapy (RT) in patients with atypical meningioma remains controversial. The goal of this work was to report the impact of timing of RT on outcomes in atypical meningioma.

Suprasellar ganglioglioma with unusual diffuse involvement of the entire optico-chiasmal hypothalamic pathway

Gangliogliomas (GG) are mixed glioneuronal tumors of the central nervous system (CNS), occurring mostly in the pediatric population, with common sites being temporal lobes and less commonly in the frontal and parietal lobes. We report a case of a 7-year-old child who presented with bilateral visual defects for 6 months. Magnetic resonance imaging (MRI) of the brain revealed an intensely enhancing mass lesion with calcification in the sellar and suprasellar region involving the optic chiasm and the left optic nerve. The mass showed almost bilaterally symmetrical diffuse spread along the optic tracts posteriorly and hypothalamus, temporal lobes, thalami and the basal ganglia. The lesion was radiologically indistinguishable from chiasmatic astrocytoma or a germ cell tumor but histopathological features were of a ganglioglioma. While a few optic apparatus gangliogliomas have been reported in the literature, such widespread diffuse involvement of the entire optico-chiasmal hypothalamic pathway is unusual.     

Prospective assessment of activities of daily living using Modified Barthel’s Index in children and young adults with low-grade gliomas treated with stereotactic conformal radiotherapy

Purpose To report prospective evaluations of activities of daily living (ADL) in young patients with low-grade gliomas treated with stereotactic conformal radiotherapy (SCRT). Materials and methods Between April 2001 and February 2008, 38 children and young adults (age 5–25 years, median 12.5 years) with low-grade gliomas with residual/progressive disease and treated with SCRT were accrued in a prospective protocol. Patients underwent baseline and follow-up ADL assessments by the modified Barthel’s battery, which comprises domains of personal hygiene, bathing self, feeding, toilet, stair climbing, dressing, bowel control, bladder control, ambulation, and chair-bed transfer. Result The patient population consisted of 38 patients (male 29, female 9) with a diagnosis of residual or progressive low-grade glioma (pilocytic astrocytoma in 27, fibrillary astrocytoma in 5, ependymoma in 4, and oligodendroglioma and pleomorphic xanthoastrocytoma in 1 each). Three patients were visually handicapped. Mean of total modified Barthel’s ADL score (Barthel’ Index, BI) at baseline before staring SCRT was 94.5 (standard deviation 14.8, range 45–100). At 2-year and 3-year follow-up, mean BI was 97.1 and 99, respectively. At baseline pre-radiotherapy assessment, patients with impaired visual function and with low performance status (Karnofsky performance score, KPS < 70) had significantly lower BI than those with normal vision (P ≤ 0.001) and with good performance status (P = 0.001). On follow-up, maximum improvement in individual BI was seen in the ambulation-related domain in patients with impaired visual function (P = 0.027), low KPS (P = 0.015), and age less than 13 years (P = 0.103). The mean pre-radiotherapy baseline BI of three patients, who eventually developed local recurrence, was only 64 (SD 32.1) as compared with a baseline score of 97.18 seen in patients whose tumor remained controlled at follow-up (P ≤ 0.001). Conclusions Young patients with low-grade gliomas after surgical intervention had a lower than normal BI before starting radiotherapy, suggesting a decrease in ADL possibly due to tumor- and surgery-related factors. At 2-year and 3-year follow-up after SCRT, there was no further decrease in mean BI. A significant improvement in BI was seen in visually handicapped patients, patients with poor performance status, and younger patients. Patients who developed tumor recurrence at follow-up had a significantly lower BI at baseline than patients with controlled disease (P ≤ 0.001). Presented at the 39th Congress of the International Society of Pediatric Oncology, Mumbai, 1st–3rd November, 2007.     

Dose-Constraint Model to Predict Neuroendocrine Dysfunction in Young Patients With Brain Tumors: Data From a Prospective Study

PurposeWe report on a possible dose-constraint model to predict long-term neuroendocrine dysfunction after cranial irradiation in children and young adults with benign and low-grade brain tumors treated with stereotactic conformal radiation therapy (RT) in a prospective clinical trial.Methods and materialsPatients treated with stereotactic conformal RT (54 Gy in 30 fractions) were included for analysis if their co-registered planning computed tomography and magnetic resonance imaging scans were available, along with baseline and post-RT endocrine assessment for at least 2 years. The hypothalamus–pituitary axis (HPA) was contoured on the fused computed tomography–magnetic resonance imaging data set. Worsening of endocrine function was defined biochemically as a new onset endocrine deficit or worsening of preexisting endocrine deficit. Dosimetric indices of HPA, extracted using cumulative dose-volume histograms, were correlated with worsening endocrine function using logistic regression analysis.ResultsA total of 51 patients (median age: 13 years; range, 5-25 years) were included. Worsening post-RT endocrine levels were seen in 27 of 51 patients (47%). Growth hormone was the most commonly affected (70%), followed by cortisol (44%), gonadotropin (40%), and thyroxine (7%). The mean of the maximum and minimum doses to HPA was 42.1 Gy and 35.7 Gy, respectively. For patients with worsening endocrine levels, the mean maximum dose to HPA was 46.6 Gy compared with 36.5 Gy in patients with stable functions. The mean minimum dose to HPA was also higher (40.5 Gy vs 29.6 Gy) in patients with endocrine dysfunction. Logistic regression analysis identified the volume of HPA receiving 50% of the prescribed dose as the only statistically significant parameter predicting endocrine dysfunction. A dose of ≥27 Gy to any volume of HPA was associated with a 4-fold increase in risk of endocrine dysfunction (odds ratio: 4.05; 95% confidence interval, 1.07-15.62; P = .038).ConclusionsOur prospective longitudinal study demonstrates the feasibility of HPA avoidance using modern, high-precision, conformal RT techniques and correlates HPA dosimetry with neuroendocrine dysfunction. We suggest restricting HPA doses to <27 Gy to minimize the risk of post-RT neuroendocrine deficits.     

Temozolomide-induced myelotoxicity and single nucleotide polymorphisms in the MGMT gene in patients with adult diffuse glioma: a single-institutional pharmacogenetic study

Journal of Neuro-Oncology - Nearly 10% of patients with adult diffuse glioma develop clinically significant myelotoxicity while on temozolomide (TMZ) leading to treatment interruptions. This study...