For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis.

A B S T R A C T PurposeRadiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O 6 -methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. Patients and MethodsThis phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of Ն 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. ResultsA total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P ϭ .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P ϭ .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P Ͻ .001), PFS (8.7 v 5.7 months; HR, 1.63; P Ͻ .001), and response (P ϭ .012). There was increased grade Ն 3 toxicity in arm 2 (34% v 53%; P Ͻ .001), mostly lymphopenia and fatigue. ConclusionThis study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.

The farnesoid X receptor (FXR) is a nuclear receptor that plays key roles in hepatoprotection by maintaining the homeostasis of liver metabolism. FXR null mice display strong hepatic inflammation and develop spontaneous liver tumors. In this report, we demonstrate that FXR is a negative modulator of nuclear factor B (

IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

A B S T R A C T PurposeA prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). Patients and MethodsEligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age Ն 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. ResultsIn all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT ϩ PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P ϭ .33; log-rank P ϭ .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT ϩ PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P ϭ .06; log-rank P ϭ .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT ϩ PCV. For 2-year survivors (n ϭ 211), the probability of OS for an additional 5 years was 74% with RT ϩ PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P ϭ .02). ConclusionPFS but not OS was improved for adult patients with LGG receiving RT ϩ PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.

Background A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the bloodbrain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. Methods and Materials NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy×15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m2/day× 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150–200 mg/m2/day ×5 days/month) could be continued for as long as 6 months after WBRT þ SRS. The primary endpoint was OS. Results After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT þ SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). Conclusion The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

Efficient separation of photogenerated electrons and holes, and associated surface reactions, is a crucial aspect of efficient semiconductor photocatalytic systems employed for photocatalytic hydrogen production. A new CoO /TiO /Pt photocatalyst produced by template-assisted atomic layer deposition is reported for photocatalytic hydrogen production on Pt and CoO dual cocatalysts. Pt nanoclusters acting as electron collectors and active sites for the reduction reaction are deposited on the inner surface of porous TiO nanotubes, while CoO nanoclusters acting as hole collectors and active sites for oxidation reaction are deposited on the outer surface of porous TiO nanotubes. A CoO /TiO /Pt photocatalyst, comprising ultra-low concentrations of noble Pt (0.046 wt %) and CoO (0.019 wt %) deposited simultaneously with one atomic layer deposition cycle, achieves remarkably high photocatalytic efficiency (275.9 μmol h ), which is nearly five times as high as that of pristine TiO nanotubes (56.5 μmol h ). The highly dispersed Pt and CoO nanoclusters, porous structure of TiO nanotubes with large specific surface area, and the synergetic effect of the spatially separated Pt and CoO dual cocatalysts contribute to the excellent photocatalytic activity.

Purpose Previous recursive partitioning analysis (RPA) of patients with malignant glioma (glioblastoma multiforme [GBM] and anaplastic astrocytoma [AA]) produced six prognostic groups (I-VI) classified by six factors1. We sought here to determine whether the classification for GBM could be improved by using an updated RTOG GBM database excluding AA and by considering additional baseline variables. Patients and Methods The new analysis considered 42 baseline variables and 1672 GBM patients from the expanded RTOG glioma database. Patients receiving radiation only were excluded such that all patients received radiation+carmustine. “Radiation dose received” was replaced with “radiation dose assigned.” The new RPA models were compared to the original model by applying to a test dataset comprising 488 patients from six other RTOG trials. Fitness of the original and new models was evaluated using explained variation. Results The original RPA model explained more variations in survival in the test dataset than did the new models (20% vs. 15%) and was therefore chosen for further analysis. It was reduced by combining classes V and VI to produce three prognostic classes (III, IV, V+VI), as classes V and VI had indistinguishable survival in the test dataset. The simplified model did not further improve performance (explained variation 18% vs. 20%) but is easier to apply because it involves only four variables:age, performance status, extent of resection, and neurologic function. Applying this simplified model to the updated GBM database resulted in three distinct classes with median survival times of 17.1, 11.2, and 7.5 months for classes III, IV, and V+VI, respectively. Conclusions The final model, the simplified original RPA model combining classes V and VI, resulted in three distinct prognostic groups defined by age, performance status, extent of resection, and neurologic function. This classification will be used in future RTOG GBM trials.