Addition Of PCV Research Articles

NCOG-12. COGNITIVE FUNCTION (CF) & QUALITY OF LIFE (QOL) IN PATIENTS TREATED WITH PROCARBAZINE, CCNU, & VINCRISTINE (PCV) + RADIOTHERAPY (RT) VS. RT FOR ANAPLASTIC OLIGODENDROGLIOMA (AO) ON NRG RTOG TRIAL 9402

Abstract BACKGROUND PCV+RT substantially prolongs survival in AO patients, but long-term CF and QOL implications are unclear. We compared CF and QOL by treatment arm in RTOG 9402 participants and evaluated the impact that baseline characteristics had on CF, QOL, and survival. METHODS CF and QOL were evaluated using the Mini Mental State Exam (MMSE) and Brain-Quality of Life (B-QOL) scale at baseline and annually. Scores were analyzed between treatment arms at each time point for patients with ≥ 10 years of follow-up data. Shared parameter models evaluated MMSE and B-QOL scores and survival for all patients. RESULTS 42/148 (28.4%) participants in PCV+RT and 20/143 (14%) in RT alone arms survived ≥ 10 years. 35/42 and 39/42 (PCV+RT) and 18/20 and 17/20 (RT) participants completed baseline B-QOL and MMSE assessments, respectively. B-QOL scores did not differ between treatment groups at any time-point. Among 16 patients (10 PCV+RT, 6 RT) who completed year 10 MMSE evaluations, mean MMSE score at 10 years was higher in the RT arm (29.83 [95% CI 22.1, 30.0] vs. 26.50 [95% CI 29.4, 30.0], P= 0.04). Change in MMSE and B-QOL scores from baseline did not differ significantly between treatment groups at any time. In shared parameter models including all patients with baseline assessments, MMSE and B-QOL scores decreased over time (MMSE P= 0.0189, B-QOL P= 0.0005), but this did not differ by treatment group (MMSE P= 0.5727, B-QOL P= 0.3592). Younger age and higher KPS predicted better scores (MMSE P < 0.0001, P = 0.0002; B-QOL P = 0.0043, P = 0.0007). PCV+RT predicted better survival in both models. CONCLUSIONS PCV+RT improves survival in AO. Shared parameter models show decrease in MMSE and B-QOL over time. However, relative to RT alone, the addition of PCV did not impact change in CF and QOL over time.

Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma

NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

Updated predictive analysis of the WHO-defined molecular subgroups of low-grade gliomas within the high-risk treatment arms of NRG Oncology/RTOG 9802.

2002 Background: This study sought to update the predictive significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/noncodel, and IDHmt/codel) in the subset of specimens available for analysis in NRG Oncology/RTOG 9802, a phase III trial of high-risk low-grade gliomas (LGGs) treated with radiation (RT) with and without PCV after biopsy/surgical resection. Notably, this is the first phase III study to evaluate the predictive value of the WHO subgroups in LGGs using prospectively-collected, well-annotated long-term overall survival data, in a post-hoc analysis. Methods: IDH1/2 mutation status was determined by immunohistochemistry and/or next-generation sequencing. 1p/19q status was determined by Oncoscan and/or 450K methylation data. Treatment effects on overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a secondary and exploratory analysis. Results: Of all the randomized eligible high-risk G2 patients (N = 251) in NRG Oncology/RTOG 9802, 106(42%) patients had tissue available with sufficient quality DNA for profiling. Of these, 80(75%) were IDHmut; 43(41%) were IDHmut/non-co-deleted, 37(35%) were IDHmut/co-deleted, and 26(24%) were IDHwt. Upon univariate analyses, no significant difference in either PFS or OS was observed with the addition of PCV in the IDHwt subgroup. Both the IDHmut/non-co-deleted and IDHmut/co-deleted subgroups were significantly correlated with longer PFS (HR = 0.32; p = 0.003; HR = 0.13; p &lt; 0.001) and OS (HR = 0.38; p = 0.013; HR = 0.21; p = 0.029) in the RT plus PCV arm, respectively. Conclusions: Our analyses suggest that both IDHmut/non-co-deleted and IDHmut/co-deleted subgroups received benefit from treatment with PCV although sample size is limited and analyses are post-hoc. Our results also support the notion that IDHwt high-risk LGG patients do not benefit from the addition of PCV to RT. Funding: U10CA180868, U10CA180822, and U24CA196067. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01, BTFC, OSU-CCC (all to AC). Clinical trial information: NCT00003375.

Genetic landscape of extreme responders with anaplastic oligodendroglioma.

BackgroundThe NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. Methods: We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts. Results: Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).ConclusionsThese findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.

Use of pyrocatechol violet as an effective redox additive for highly promoting the supercapacitor performances

In present work, we demonstrate a simple but effective redox additive of pyrocatechol violet (abbr. PCV) to largely promote the capacitive performances especially when carried out in three different kinds of electrolytes (H2SO4, Na2SO4 and KOH), mostly due to its fast electron and proton transfer occurring in the electrode/electrolyte interface. It reveals that the PCV dosage incorporated into electrolyte plays a crucial role in the determination of capacitive performance. When conducted in a two-electrode system, incorporating 0.06 mol L−1 PCV into 1 mol L−1 H2SO4 can achieve large capacitance up to 200 F g−1, which is almost 2.06 times than the one without the addition of PCV; besides, the corresponding energy density is of 28 Wh kg−1 (also increasing 2 times). What’s more, PCV has been extended as the redox additive in other electrolytes such as Na2SO4 and KOH, and remarkable promotion in capacitance and energy density also occur, well evincing the high efficiency and universal applicability of PCV for the large promotion of supercapacitors’ performances due to its prominent electrochemical reversibility and high solubility.

The effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: Secondary analysis of RTOG 98-02.

2047 Background: The addition of PCV chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS) and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin Oncol 26: 2008). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival. Methods: 251patients with WHO grade II glioma and age &gt; 40 with any extent of resection, or age &lt; 40 with subtotal resection/biopsy were randomized to RT (54Gy) or RT + PCV. 111 patients with age &lt; 40 and gross total resection were observed. CF was assessed by mini-mental status exam (MMSE)at baseline and years 1, 3, and 5 for patients without progression. Change in MMSE score from baseline of &gt; 3 points was considered clinically significant. Results: Overall, very few patients experienced significant decline in MMSE score, with a median follow-up time of 9.7 years for alive patients. There were no significant differences in the proportion of patients experiencing MMSE decline between study arms at any time point. The table below summarizes MMSE change from baseline over time. Neither baseline MMSE score nor change in MMSE at year 1 significantly predicted for OS or PFS, but there was a trend towards worse OS for patients with MMSE loss of ≥ 2 points [HR 1.73, 95% CI (0.86, 3.47), p=0.12]. Conclusions: The MMSE is a relatively insensitive tool that has not been validated in patients receiving cranial RT, and subtle changes in CF may have been missed. However, the addition of PCV to RT for low grade glioma did not result in significantly higher rates of MMSE decline than RT alone or observation. There was a trend towards an MMSE decline of ≥ 2 points at year 1 predicting for worse OS. [Table: see text]

Current Strategies in Treatment of Oligodendroglioma: Evolution of Molecular Signatures of Response

Oligodendroglioma frequently (> or = 70%) responds to radiation and chemotherapy, and is the first CNS neoplasm in which a genetic signature (1p and 19q deletion) has been associated with outcome within the context of large clinical trials. Current translational investigations focus on deletions or mutations of potential tumor suppressor genes, epigenetic alterations, amplification or mutation of growth factor and regulatory genes, and characterization of signaling events and regulatory protein expression. The most compelling data has involved 1p and 19q loss, which is observed in over 50% of anaplastic oligodendrogliomas. In two randomized phase III trials (Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951), the addition of neoadjuvant or adjuvant procarbazine, lomustine, and vincristine (PCV; respectively) to radiotherapy did not produce superior survival as compared with radiotherapy alone. A modest increase in progression-free survival was observed with the addition of PCV, but at the cost of increased toxicity. Combined 1p and 19q loss identified a favorable prognostic group in both studies, which appeared to be independent of treatment arms. However, it is unclear whether these deletions represent surrogate markers of a favorable biologic tumor behavior, or are predictive of outcome after specific treatment. Currently, there is insufficient data to allow therapeutic decisions to be made solely on the basis of 1p and 19q gene deletion status. Future phase III trials are evaluating other chemotherapeutic and targeted agents, including temozolomide, and include correlative investigations of aberrant molecular events in these neoplasms, which may lead to future therapeutic strategies that are based on specific molecular signatures.

PCV and modified hill procedure as surgical treatment of reflux esophagitis: results in 108 patients.

AbstractParietal cell vagotomy (PCV) and the Hill antireflux procedure were used in 108 patients with reflux esophagitis. The addition of PCV provides better access to the cardia and ensures that more extensive vagotomy than intended does not occur. Furthermore, a reduction in the basal acid output (BAO) is preferable. In patients still symptomatic after surgery, the BAO was unchanged, while in those without postoperative symptoms a significant decrease in BAO was found (p &lt; 0.01).Gastroesophageal sphincter pressure was significantly higher postoperatively in all patients. Complications were few; 92% were asymptomatic at 2 months, 88% at 1 year, and 71% at 2 years. A remarkable reduction in pulmonary symptoms after operation indicates a close relationship between chronic pulmonary disease and gastroesophageal reflux in some patients.