There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

methods Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. results A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.

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Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nelia and Amadeo Barletta Foundation, Schering-Plough.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(09)70025-7.pdf

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial

https://www.genome.gov/Pages/Newsroom/Webcasts/2010ScienceReportersWorkshop/Panel5_integrated_genome_analysis_subtypes_of_glio.pdf

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Clinical Outcomes for a Novel 6 Degrees of Freedom Image Guided Immobilization and Localization Method for Frameless Radiosurgery for Brain Metastases

2037 Background: Treatment of high-grade glioma consists of fractionated radiation therapy (RT) ± chemotherapy. The incidence/significance of NT in this disease is not known. We evaluated the relat...

/pdf/acute-neurological-toxicity-nt-and-long-term-outcomes-in-3z4aodjloo.pdf

Acute neurological toxicity (NT) and long-term outcomes in high-grade glioma RTOG trials.

Purpose: Erectile dysfunction (ED) is the most common complication of prostate-cancer radiotherapy (RT) and the major mechanism is radiation-induced neurovascular bundle (NVB) damage. However, the localization of the NVB remains challenging. This study's purpose is to accurately localize 3D NVB by integrating MR and transrectal ultrasound (TRUS) images through MR-TRUS fusion. Methods: T1 and T2-weighted MR prostate images were acquired using a Philips 1.5T MR scanner and a pelvic phase-array coil. The 3D TRUS images were captured with a clinical scanner and a 7.5 MHz biplane probe. The TRUS probe was attached to a stepper; the B-mode images were captured from the prostate base to apex at a 1-mm step and the Doppler images were acquired in a 5-mm step. The registration method modeled the prostate tissue as an elastic material, and jointly estimated the boundary condition (surface deformation) and the volumetric deformations under elastic constraint. This technique was validated with a clinical study of 7 patients undergoing RT treatment for prostate cancer. The accuracy of our approach was assessed through the locations of landmarks, as well as previous ultrasound Doppler images of patients. Results: MR-TRUS registration was successfully performed for all patients. The mean displacement of the landmarks betweenmore » the post-registration MR and TRUS images was 1.37±0.42 mm, which demonstrated the precision of the registration based on the biomechanical model; and the NVB volume Dice Overlap Coefficient was 92.1±3.2%, which demonstrated the accuracy of the NVB localization. Conclusion: We have developed a novel approach to improve 3D NVB localization through MR-TRUS fusion for prostate RT, demonstrated its clinical feasibility, and validated its accuracy with ultrasound Doppler data. This technique could be a useful tool as we try to spare the NVB in prostate RT, monitor NBV response to RT, and potentially improve post-RT potency outcomes.« less

Walter J. Curran

Papers

Clinical Outcomes for a Novel 6 Degrees of Freedom Image Guided Immobilization and Localization Method for Frameless Radiosurgery for Brain Metastases

Acute neurological toxicity (NT) and long-term outcomes in high-grade glioma RTOG trials.

SU-D-9A-06: 3D Localization of Neurovascular Bundles Through MR-TRUS Registration in Prostate Radiotherapy

Short Course Radiation Therapy for Acoustic Neuromas

A simple method for calculation of prescribed dose for total body photon irradiation