Walter J. Curran

Bio: Walter J. Curran is an academic researcher from Emory University. The author has contributed to research in topics: Radiation therapy & Lung cancer. The author has an hindex of 86, co-authored 742 publications receiving 38522 citations. Previous affiliations of Walter J. Curran include Fox Chase Cancer Center & Washington University in St. Louis.

A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma

Abstract: Background Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. Methods In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary ...

Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study

Abstract: Summary Background We aimed to compare overall survival after standard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer. Methods In this open-label randomised, two-by-two factorial phase 3 study in 185 institutions in the USA and Canada, we enrolled patients (aged ≥18 years) with unresectable stage III non-small-cell lung cancer, a Zubrod performance status of 0–1, adequate pulmonary function, and no evidence of supraclavicular or contralateral hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All patients also received concurrent chemotherapy with 45 mg/m 2 paclitaxel and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel (200 mg/m 2 ) and carboplatin (AUC 6). Randomisation was done with permuted block randomisation methods, stratified by radiotherapy technique, Zubrod performance status, use of PET during staging, and histology; treatment group assignments were not masked. Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy. The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary. For patients assigned to receive cetuximab, 400 mg/m 2 cetuximab was given on day 1 followed by weekly doses of 250 mg/m 2 , and was continued through consolidation therapy. The primary endpoint was overall survival. All analyses were done by modified intention-to-treat. The study is registered with ClinicalTrials.gov, number NCT00533949. Findings Between Nov 27, 2007, and Nov 22, 2011, 166 patients were randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up for the radiotherapy comparison was 22·9 months (IQR 27·5–33·3). Median overall survival was 28·7 months (95% CI 24·1–36·9) for patients who received standard-dose radiotherapy and 20·3 months (17·7–25·0) for those who received high-dose radiotherapy (hazard ratio [HR] 1·38, 95% CI 1·09–1·76; p=0·004). Median follow-up for the cetuximab comparison was 21·3 months (IQR 23·5–29·8). Median overall survival in patients who received cetuximab was 25·0 months (95% CI 20·2–30·5) compared with 24·0 months (19·8–28·6) in those who did not (HR 1·07, 95% CI 0·84–1·35; p=0·29). Both the radiation-dose and cetuximab results crossed protocol-specified futility boundaries. We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups. By contrast, the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects (205 [86%] of 237 vs 160 [70%] of 228 patients; p vs three patients; cetuximab comparison: ten vs five patients). There were no differences in severe pulmonary events between treatment groups. Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received standard-dose treatment (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p Interpretation 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer, and might be potentially harmful. Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients. Funding National Cancer Institute and Bristol-Myers Squibb.

Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non–Small-Cell Lung Cancer

Abstract: Purpose The previous individual patient data meta-analyses of chemotherapy in locally advanced non–small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy. Methods Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity. Results Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemother...

I and i

Abstract: 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 …

Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

Abstract: 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.

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

Abstract: 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%.

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

Abstract: 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.