Gliadel Wafer Implantation Combined With Standard Radiotherapy and Concurrent Followed by Adjuvant Temozolomide for Treatment of Newly Diagnosed High-Grade Glioma: A Systematic Literature Review

Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted

Gliadel Wafer Implantation Combined With Standard Radiotherapy and Concurrent Followed by Adjuvant Temozolomide for Treatment of Newly Diagnosed High-Grade Glioma: A Systematic Literature Review

Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted

Atypical Teratoid Rhabdoid Tumor: two Case Reports and an Analysis of Adult Cases With Implications for Pathophysiology and Treatment

We present the first quantitative analysis of atypical teratoid rhabdoid tumors (ATRT) in adults, including two patients from our own institutions. These are of interest as one occurred during pregnancy and one is a long-term survivor. Our review of pathological findings of 50 reported cases of adult ATRT leads us to propose a solely ectodermal origin for the tumor and that epithelial-mesenchymal transition (EMT) is a defining feature. Thus, the term ATRT may be misleading. Our review of clinical findings shows that ATRT tends to originate in mid-line structures adjacent to the CSF, leading to a high rate of leptomeningeal dissemination. Thus, we hypothesize that residual undifferentiated ectoderm in the circumventricular organs, particularly the pituitary and pineal glands, is the most common origin for these tumors. We note that if growth is not arrested soon after diagnosis, or after the first relapse/progression, death is almost universal. While typically rapidly fatal (as in our first case), long-term remission is possible (as in our second). Significant predictors of prognosis were the extent of resection and the use of chemotherapy. Glial differentiation (GFAP staining) was strongly associated with leptomeningeal metastases (chi-squared p = 0.02) and both predicted markedly worse outcomes. Clinical trials including adults are rare. ATRT is primarily a disease of infancy and radiotherapy is generally avoided in those aged less than 3 years old. Treatment options in adults differ from infants in that cranio-spinal irradiation is a viable adjunct to systemic chemotherapy in the adult population. Given the grave prognosis, this combined approach appears reasonable. As effective chemotherapy is likely to cause myelosuppression, we recommend that stem-cell rescue be available locally

Prospectus, February 15, 1984

ELECTION RESULTS; News Digest; Blacks added to local history; Letter from the editor; Letter to the editor; Letter to the editor; PC Happenings: Real estate review workshop, Lifelong Learners to meet, Story shop stimulates young writers, EMT assessment workshop offered; Gameroom damage--why!!; Student award; Letter to the editor; Roberts nominated; Book Review: Making College Pay Off ; Reflections and contemplations; Student needs witness; Division chairman believes in Parkland; \u27Images\u27 needs you; Dodd explains his position on Miller; Did You Know...; Coach encouraged at team\u27s success; Wheelchair games postponed; Fewer students at Parkland; Bushman and Gunter; Survival trip taken; \u27Shadows Beyond the Benefit....\u27 entices thinking; Davis says farewell; Eclectic collection of art; Creative Corner...Especially for you!!: Freedom, To God, A Worn-out photograph, Memories, Clouds, The Spreading Flame, Why, Haunting Beauty, Lost Love, The Wheel of Fortune, What Is the Vocal?, The Petals of Marie, Unknown, No Defeat, A Tribute to Fallen Hero; John Watching ; King led the way for blacks in the 1960\u27s; Anti-discrimination pledge signed; Rosa Parks remembered; Black colleges pitch into nationwide crisis; Play review; Dream becomes day-to-day reality; Increase Awareness of Financial Aid Available; Colored Girls stresses stereotyping; Yaxley scholarship; Black collection extensive; \u27Operation Snowball\u27 helps teens help themselves; In the Library-- P Section; Question: Do you think we will ever attain world peace?; Classifieds; \u27Four Seasons\u27 blast of fresh air; Campus Paperback Bestsellers; New & Recommended; Another political album for U2 with \u27Under a Blood Red Sky\u27; New Dorothy after 45 years; Institute shows rare independent British films; Film festival schedule; MTV--a hit that\u27s here to stay; Utopia reminds us that it is 1984; Silkwood should be seen by all; Nicaragua, a problem the U.S. should study now; Trout remembers when; I.M. News; Wulf recalls coaching days; Carper recalls Parkland; Martin wins triple jump at meet; Composite athletic schedule; Competition aids inequalityhttps://spark.parkland.edu/prospectus_1984/1031/thumbnail.jp

Phase III Randomized Trial Comparing the Efficacy of Cediranib as Monotherapy and in Combination With Lomustine Versus Lomustine Alone in Patients With Recurrent Glioblastoma

Purpose: A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods: Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m2); (3) lomustine (110 mg/m2) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans. Results: The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI. Conclusion: This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects

Embedded pitch adapters: a high-yield interconnection solution for strip sensors

A proposal to fabricate large area strip sensors with integrated, or embedded, pitch adapters is presented for the End-cap part of the Inner Tracker in the ATLAS experiment. To implement the embedded pitch adapters, a second metal layer is used in the sensor fabrication, for signal routing to the ASICs. Sensors with different embedded pitch adapters have been fabricated in order to optimize the design and technology. Inter-strip capacitance, noise, pick-up, cross-talk, signal efficiency, and fabrication yield have been taken into account in their design and fabrication. Inter-strip capacitance tests taking into account all channel neighbors reveal the important differences between the various designs considered. These tests have been correlated with noise figures obtained in full assembled modules, showing that the tests performed on the bare sensors are a valid tool to estimate the final noise in the full module. The full modules have been subjected to test beam experiments in order to evaluate the incidence of cross-talk, pick-up, and signal loss. The detailed analysis shows no indication of cross-talk or pick-up as no additional hits can be observed in any channel not being hit by the beam above 170 mV threshold, and the signal in those channels is always below 1% of the signal recorded in the channel being hit, above 100 mV threshold. First results on irradiated mini-sensors with embedded pitch adapters do not show any change in the interstrip capacitance measurements with only the first neighbors connected

NRG/RTOG 0837: Randomized, Phase II, Double-Blind, Placebo-Controlled Trial of Chemoradiation With or Without Cediranib in Newly Diagnosed Glioblastoma

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided RESULTS: One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm ( CONCLUSIONS: This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms

Study of surface properties of ATLAS12 strip sensors and their radiation resistance

A radiation hard nþ-in-p micro-strip sensor for the use in the Upgrade of the strip tracker of the ATLAS experiment at the High Luminosity Large Hadron Collider (HL-LHC) has been developed by the “ATLAS ITk Strip Sensor collaboration” and produced by Hamamatsu Photonics. Surface properties of different types of end-cap and barrel miniature sensors of the latest sensor design ATLAS12 have been studied before and after irradiation. The tested barrel sensors vary in “punchthrough protection” (PTP) structure, and the end-cap sensors, whose stereo-strips differ in fan geometry, in strip pitch and in edge strip ganging options. Sensors have been irradiated with proton fluences of up to 1 1016 neq/cm2 , by reactor neutron fluence of 1 1015 neq/cm2 and by gamma rays from 60Co up to dose of 1 MGy. The main goal of the present study is to characterize the leakage current for microdischarge breakdown voltage estimation, the inter-strip resistance and capacitance, the bias resistance and the effectiveness of PTP structures as a function of bias voltage and fluence. It has been verified that the ATLAS12 sensors have high breakdown voltage well above the operational voltage which implies that different geometries of sensors do not influence their stability. The inter-strip isolation is a strong function of irradiation fluence, however the sensor performance is acceptable in the expected range for HL-LHC. New gated PTP structure exhibits low PTP onset voltage and sharp cut-off of effective resistance even at the highest tested radiation fluence. The inter-strip capacitance complies with the technical specification required before irradiation and no radiation-induced degradation was observed. A summary of ATLAS12 sensors tests is presented including a comparison of results from different irradiation sites. The measured characteristics are compared with the previous prototype of the sensor design, ATLAS07

Charge collection and field profile studies of heavily irradiated strip sensors for the ATLAS inner tracker upgrade

The ATLAS group has evaluated the charge collection in silicon microstrip sensors irradiated up to a fluence of 1×1016 neq/cm2, exceeding the maximum of 1.6×1015 neq/cm2 expected for the strip tracker during the high luminosity LHC (HL-LHC) period including a safety factor of 2. The ATLAS12, n+-on-p type sensor, which is fabricated by Hamamatsu Photonics (HPK) on float zone (FZ) substrates, is the latest barrel sensor prototype. The charge collection from the irradiated 1×1 cm2 barrel test sensors has been evaluated systematically using penetrating β-rays and an Alibava readout system. The data obtained at different measurement sites are compared with each other and with the results obtained from the previous ATLAS07 design. The results are very consistent, in particular, when the deposit charge is normalized by the sensor's active thickness derived from the edge transient current technique (edge-TCT) measurements. The measurements obtained using β-rays are verified to be consistent with the measurements using an electron beam. The edge-TCT is also effective for evaluating the field profiles across the depth. The differences between the irradiated ATLAS07 and ATLAS12 samples have been examined along with the differences among the samples irradiated with different radiation sources: neutrons, protons, and pions. The studies of the bulk properties of the devices show that the devices can yield a sufficiently large signal for the expected fluence range in the HL-LHC, thereby acting as precision tracking sensors