Showing papers by "Barbara Fisher published in 2015"

Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

Abstract: Purpose Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values ( P Conclusions The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls ( P

Atct-09idh1 r132h mutations in nrg oncology/rtog 9802: phase iii study of radiation therapy (rt) alone vs rt plus procarbazine, ccnu, and vincristine (pcv) in patients with low grade glioma (lgg).

Abstract: BACKGROUND: RT/PCV produces longer progression-free (PFS) and overall survival (OS) in LGG patients versus RT alone. Molecular markers have not been reported previously. METHODS: 251 eligible LGG patients were randomized to receive RT or RT/PCV. Immunohistochemistry, performed with the monoclonal antibody against IDH1 R132H, was scored positive when tumor cells showed cytoplasmic staining. Wilcoxon tests were performed to assess PFS and OS for IDH1-R132H positive vs negative patients, and, for IDH1-R132H mutated patients, for differences by treatment arm. RESULTS: Tissue suitable for IDH-R132H immunohistochemistry was interpretable for 113 (57/126 [45%] and 56/125 [45%]) patients in the RT vs RT/PCV arms, respectively. IDH1-R132H mutations were detected in 35/57 (61.4%) and 36/56 (64.3%) in the RT and RT/PCV arms, respectively, and in 77.6%, 53.8% and 48.0% of patients with oligodendroglioma, oligoastrocytoma, and astrocytoma, respectively. For patients without vs with IDH1-R132H mutations: median PFS was 1.5 vs 7.6 years (p < 0.001); and OS was 5.1 vs 13.1 years, respectively (p = 0.002). For patients with IDH1-R132H mutations: median, 5-year, and 10-year PFS were 4.7 years, 43%, and 21% in the RT arm, vs not reached (NR) (7.6+ years), 75%, and 64% with RT /PCV, respectively (p = 0.003). For patients with IDH1-R132H mutations: median, 5-year, and 10-year OS were 10.1 years, 69%, and 53% with RT, and NR (11.3+ years), 83%, and 75% with RT + PCV (p = 0.04). Tissue sufficient for determination of other genetic alterations was available in only 25% of patients, so reliable assessment is not feasible. CONCLUSIONS: IDH1-R132H mutations are associated with prolonged PFS and OS, regardless of treatment. In patients with IDH1-R132H mutations, RT + PCV is associated with longer PFS and OS compared with RT alone. SUPPORT: This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the National Cancer Institute (NCI).