Trial In October Research Articles

Neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor positive breast cancers: the Neo-RT feasibility study

AimsTo establish safety and feasibility of delivering neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor positive breast cancers with palpable size 20mm or greater, for which radiotherapy might facilitate more conservative surgery. Materials and MethodsA single arm feasibility study was conducted. Patients received whole breast radiotherapy with or without radiotherapy to nodal areas. Dose/fractionation was 40Gy in 15 fractions over 3 weeks, with or without either simultaneous integrated boost to 48Gy, or sequential boost, to the tumour bed. This was followed by endocrine treatment for 20 weeks, then surgery. The primary endpoint of the study was proportion of patients successfully completing neo-adjuvant radiotherapy and endocrine treatment followed by breast surgery. Response and toxicity endpoints including mastectomy rate, peri/postoperative complications, and pathological response were also evaluated.The primary analysis is descriptive. The study regimen would be considered feasible if more than 70% of patients completed treatment, while it might not be considered feasible if less than 50% did so. With a one sided 5% significance level and 80% power, a maximum of 43 patients would be required to detect a rate of ≤50% vs ≥70%. Results14 patients were recruited of the planned 43. Due to slow recruitment particularly during the COVID-19 pandemic, the decision was made to stop the trial in October 2021. One registered patient was found to be ineligible before starting treatment. 13/13 patients (100%, 90% CI: 75.3%, 100%) who received any trial treatment successfully completed all trial treatments. The lower bound of the Clopper-Pearson (exact) 90% confidence interval was 79%, indicating that the primary endpoint would have been met if the planned recruitment had been achieved. 3/13 patients underwent mastectomy. 7/13 had more conservative surgery than had been planned at baseline. 4/13 patients experienced any peri/postoperative complication. The only acute radiotherapy toxicities reported were grade 1/2 dermatitis and grade 1 fatigue. Long term breast outcomes were clinician assessed as none/mild at all timepoints in 12/13 patients. All tumours showed evidence of some pathological response to treatment, but none had pathological complete response. ConclusionsThis treatment schedule is likely feasible. It is difficult to draw strong conclusions on safety/toxicity given the small numbers, but these seem in keeping with other recent reports of neoadjuvant breast radiotherapy.

A Systematic Review of Interventions to Promote Cervical Cancer Screening among Immigrant Vietnamese Women.

Vietnamese women have a higher incidence rate of cervical cancer and are less likely to have ever been screened for cervical cancer than their White counterparts in the US. This review synthesizes findings from published interventions to promote cervical cancer screening in this vulnerable population. Articles were identified through a systematic search of PsycInfo, Embase, Pubmed, Web of Science, and the Cochrane Register of Controlled Trials in October 2022. Articles were included if they were published in a peer-reviewed journal, written in English, included one or more interventions promoting cervical cancer screening, assessed at least one outcome relevant to screening, and included a sample of ≥ 70% Vietnamese participants. Quality assessment scores were computed using the Downs and Black Checklist. Fifteen articles met review inclusion criteria. Studies were, on average, of good quality. Most studies were conducted in the US (n = 12), used a quasi-experimental design (n = 9), and employed multiple intervention strategies (n = 12). Intervention strategies included educational sessions, lay health worker (LHW) outreach, small media, mass media, patient navigation, and community or healthcare-based strategies. The most common study outcomes were screening intention and receipt. All but two studies reported improved cervical cancer screening outcomes following intervention. Findings support the effectiveness of multicomponent culturally tailored interventions to improve cervical cancer screening outcomes in immigrant Vietnamese women. Further research is needed to determine whether these interventions will be as successful in non-US countries and to address broader community- and healthcare-based factors in screening.

CTNI-53. ESTABLISHING A PHASE I AND RANDOMIZED PHASE II TRIAL OF SELINEXOR AND TEMOZOLOMIDE IN GLIOBLASTOMA

Abstract BACKGROUND Selinexor (SEL) is a first-in-class XPO1 inhibitor with potent antitumor activity via tumor suppressor protein nuclear localization and reactivation, oncoprotein translation suppression, and DNA repair inhibition. As a single agent, SEL has demonstrated adequate brain penetration and clinically relevant responses in glioblastoma. We seek to enhance the effect and benefit of SEL by priming with temozolomide (TMZ). METHODS We developed in vitro and in vivo studies to rationally design a phase I/II trial to evaluate the safety and efficacy of the sequential combination of SEL+TMZ. Sequential treatment of U87 cells and intracranial mouse xenografts demonstrated superior DNA damage (ɣH2A.X, cleaved PARP) and overall survival compared to combination or single-agent therapy (HR 0.25 [95% CI, 0.07-0.84]; p = 0.01, log-rank). We used the top-scoring pair method to identify a 6 gene-pair RNAseq signature associated with response to SEL. RESULTS Based on preclinical findings, we developed and opened a multi-institutional phase I/II clinical trial in October 2022. Eligibility includes histologically confirmed 1st recurrent MGMT promoter methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and prospective validation of a molecular signature of response. Phase I dose finding by IQ 3 + 3 (n = 12) involves TMZ 150mg/m2 on days 1-5 of a 28-day cycle plus SEL on days 8 and 15. Phase II will involve randomization (n = 72) to the RP2D of SEL+TMZ versus monotherapy TMZ. Using proportional hazards regression, RHR 0.5 with p < 0.1 will demonstrate sufficient efficacy. We have enrolled 3 participants in dose level 1 (SEL 60mg) with no dose-limiting toxicities (DLTs) observed. Additional preliminary results will be presented. CONCLUSION Preliminary results suggest that a sequential dosing regimen of SEL+TMZ is feasible and initial dose is well-tolerated and may minimize the cumulative toxicity of SEL. The trial is currently enrolling nationwide (NCI #10505, NCT05432804).

Contribution to development of remedies for COVID-19: focusing on Eritoran

Eritoran (E5564) is Eisai's in-house discovered and developed investigational Toll-Like Receptor 4 (TLR4) antagonist created with natural product organic synthesis technology. It is a structural analogue of Lipid A, which is an activator of endotoxins of bacteria. It has been previously observed to be safe in 14 clinical studies including a large Phase 3 randomized trial in severe sepsis. In order to evaluate therapeutic efficacy by eritoran, we are participating in the international network REMAP-CAP-COVID (Randomized, Embedded, Multi-factorial, Adaptive Platform-Community Acquired Pneumonia COVID) which aims for novel coronavirus medicine development through drug repurposing, and began an international collaborative clinical trial in October 2020 which is designated for confirmed novel coronavirus patients who are hospitalized and are in a progressing disease state. It is hoped that through suppressing the most upstream TLR4 activity which controls production of multiple cytokines by eritoran, the cytokine storm in patients can be suppressed and pneumonia can thus be prevented from becoming severe. On the other hand, E6011 is the only humanized anti-fractalkine (FKN) monoclonal antibody in the world created by KAN Research Institute. E6011 inhibits the tight binding of CD16-positive monocytes (a cell population that highly expresses the FKN receptor CX3CR1) to vascular endothelial cells, which are important for the local inflammatory response. This is expected to suppress the formation and exacerbation of vasculopathy in COVID-19.

Contribution to Development of Remedies for COVID-19: Focusing on Eritoran

Eritoran (E5564) is Eisai's in-house discovered and developed investigational TLR4 (Toll-Like Receptor 4) antagonist created with natural product organic synthesis technology. It is a structural analogue of Lipid A, which is an activator of endotoxins of bacteria. It has been previously observed to be safe in 14 clinical studies including a large Phase 3 randomized trial in severe sepsis. We are participating in the international network REMAP-CAP-COVID (Randomized, Embedded, Multi-factorial, Adaptive Platform-Community Acquired Pneumonia COVID) which aims for novel coronavirus medicine development through drug repurposing, and began an international collaborative clinical trial in October 2020 which is designated for confirmed novel coronavirus patients who are hospitalized and are in a progressing disease state. It is hoped that through suppressing the most upstream TLR4 activity which controls production of multiple cytokines, the cytokine storm in patients can be suppressed and pneumonia can thus be prevented from becoming severe.

Evaluation of the Effectiveness of a Novel Brain-Computer Interface Neuromodulative Intervention to Relieve Neuropathic Pain Following Spinal Cord Injury: Protocol for a Single-Case Experimental Design With Multiple Baselines.

BackgroundNeuropathic pain is a debilitating secondary condition for many individuals with spinal cord injury. Spinal cord injury neuropathic pain often is poorly responsive to existing pharmacological and nonpharmacological treatments. A growing body of evidence supports the potential for brain-computer interface systems to reduce spinal cord injury neuropathic pain via electroencephalographic neurofeedback. However, further studies are needed to provide more definitive evidence regarding the effectiveness of this intervention.ObjectiveThe primary objective of this study is to evaluate the effectiveness of a multiday course of a brain-computer interface neuromodulative intervention in a gaming environment to provide pain relief for individuals with neuropathic pain following spinal cord injury.MethodsWe have developed a novel brain-computer interface-based neuromodulative intervention for spinal cord injury neuropathic pain. Our brain-computer interface neuromodulative treatment includes an interactive gaming interface, and a neuromodulation protocol targeted to suppress theta (4-8 Hz) and high beta (20-30 Hz) frequency powers, and enhance alpha (9-12 Hz) power. We will use a single-case experimental design with multiple baselines to examine the effectiveness of our self-developed brain-computer interface neuromodulative intervention for the treatment of spinal cord injury neuropathic pain. We will recruit 3 participants with spinal cord injury neuropathic pain. Each participant will be randomly allocated to a different baseline phase (ie, 7, 10, or 14 days), which will then be followed by 20 sessions of a 30-minute brain-computer interface neuromodulative intervention over a 4-week period. The visual analog scale assessing average pain intensity will serve as the primary outcome measure. We will also assess pain interference as a secondary outcome domain. Generalization measures will assess quality of life, sleep quality, and anxiety and depressive symptoms, as well as resting-state electroencephalography and thalamic γ-aminobutyric acid concentration.ResultsThis study was approved by the Human Research Committees of the University of New South Wales in July 2019 and the University of Technology Sydney in January 2020. We plan to begin the trial in October 2020 and expect to publish the results by the end of 2021.ConclusionsThis clinical trial using single-case experimental design methodology has been designed to evaluate the effectiveness of a novel brain-computer interface neuromodulative treatment for people with neuropathic pain after spinal cord injury. Single-case experimental designs are considered a viable alternative approach to randomized clinical trials to identify evidence-based practices in the field of technology-based health interventions when recruitment of large samples is not feasible.Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000556943; https://bit.ly/2RY1jRx International Registered Report Identifier (IRRID)PRR1-10.2196/20979

TRYbeCA-1: A randomized, phase III study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441).

TPS4666 Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized Phase 2b study inpatients with advanced pancreatic cancer whose disease progressed following first-line treatment(NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. The results of this Phase 2b study provided a rationale for initiating this confirmatory Phase 3 pivotal trial (TRYbeCA-1). Methods: TRYbeCA-1 is a randomized, open-label Phase 3 trial (N = ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1; stage III-IV disease; documented evidence of disease progression; available tumor tissue; and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted which represents a conservative estimate based on the Phase 2b data and is viewed as being highly clinically relevant. An IDMC is established to review safety at regular intervals andto review efficacy data at the planned interim and final analyses. IDMC last reviewed the trial in October 2019 and suggested the trial continue as planned. Clinical trial information: NCT03665441 .

Case Report: Sustained Remission Achieved from Anti-CD19 CAR T Cell Therapy Despite Prior Treatment with Anti-CD19 Antibody Tafasitamab (MOR208) in a Patient with Relapsed and Refractory Diffuse Large B-Cell Lymphoma

Introduction: Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal antibody that targets CD19. L-MIND (NCT02399085) is an ongoing, open-label, single-arm, phase II study of Tafasitamab (TAFA) plus lenalidomide (LEN) in patients with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation (ASCT). A durable progression-free survival of 16 months in a poor-risk subgroup of patients treated with TAFA plus LEN was recently presented (Salles et al., 2019 ICML Meeting. Abstract 124). Treatment with CD19-targeted chimeric antigen receptor (CAR) T cell therapy has shown promising results for patients with R/R DLBCL after failure on ≥ 2 lines of systemic therapy (Neelapu S, et al. N Engl J Med 2017). Despite recent advances in anti-CD19 therapy, relapse remains frequent after each treatment modality. There is no clinical evidence to direct the sequencing of CAR T cell therapy after anti-CD19 therapy. Here, we present the first published case of an outcome after anti-CD19 antibody treatment TAFA/LEN as part of the L-MIND trial, followed by anti-CD19 CAR T therapy. Case Presentation: The patient is a 58 year old female who initially presented in March 2013 with an 8 cm mesenteric mass, workup revealed stage III germinal center B cell-like (GCB) DLBCL arising from follicular lymphoma, Ki-67 proliferation index 80%, and IGH/BCL2 fusion. The patient received 6 cycles of dose-adjusted R-EPOCH. Despite achieving a complete remission (CR) to this frontline therapy, the patient experienced disease relapse within two years. Subsequently, the patient received rituximab plus ifosfamide, carboplatin, and etoposide (RICE) chemotherapy, to which a second CR was achieved. The patient declined ASCT. Second relapse occurred approximately two years later. After meeting eligibility criteria, she was enrolled in the L-MIND trial in October 2017 and received TAFA plus LEN for 6 cycles (1 cycle = 28 days; TAFA 12mg/kg intravenously, weekly x 3 cycles, biweekly thereafter; LEN 25mg daily on days 1-21 of each cycle). TAFA/LEN was well tolerated. Stable disease was achieved with this investigational regimen, followed by progression in April 2018. Fourth-line treatment consisted of rituximab, gemcitabine, oxaliplatin, (R-GEM-OX) for 4 cycles, to which the patient had a partial response. Shortly thereafter, the patient received anti-CD19 CAR T therapy (axicabtagene ciloleucel [Yescarta]) in September 2018 (Figure 1). Treatment course was complicated by grade 2 cytokine release syndrome. A complete response was achieved one month after treatment, and has been sustained since then. As of this report (July 2019), patient remains without clinical evidence of relapse. Discussion: An important question to address in the era of targeted cellular therapy is: can the same tumor antigen be targeted with a different cancer immune therapy modality after disease progression following a previous therapy against that same antigen? In such a clinical scenario, there is concern for sustained antigen blockade from the prior line of therapy. In addition, there is concern for the selective pressures of prior therapy targeted against a specific antigen allowing for progression of a clone that does not express that antigen, rendering subsequent therapy against the same target ineffective (antigen escape). The half-life of TAFA is approximately 16 days, suggesting that it was eliminated prior to CAR T-cell infusion five months later. Although a biopsy was not done upon progression after TAFA, we assume that CD19 antigen escape did not account for the relapse, since the patient has achieved sustained remission with subsequent anti-CD19 CAR T cell therapy. Therefore, disease progression following treatment with anti-CD19 monoclonal antibody Tafasitamab may not preclude patients from anti-CD19 CAR T cell therapy, despite previously targeting the same antigen. Figure 1 Disclosures de Vos: Verastem: Consultancy; Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy.

Mechanisms, mishaps and manipulation of iron uptake

Mechanisms, mishaps and manipulation of iron uptake

Mobile Technology for Cognitive Assessment of Older Adults: A Scoping Review.

Background and ObjectivesThe number of people diagnosed with dementia is rising appreciably as the population ages. In an effort to improve outcomes, many have called for facilitating early detection of cognitive decline. Increased use of mobile technology by older adults provides the opportunity to deliver convenient, cost-effective assessments for earlier detection of cognitive impairment. This article presents a review of the literature on how mobile platforms—smartphones and tablets—are being used for cognitive assessment of older adults along with benefits and opportunities associated with using mobile platforms for cognitive assessment.Research Design and MethodsWe searched MEDLINE, Web of Science, PsycInfo, CINAHL, EMBASE, and Cochrane Central Register of Controlled Trials in October 2018. This search returned 7,024 articles. After removing 1,464 duplicates, we screened titles and abstracts then screened full-text for those articles meeting inclusion and exclusion criteria.ResultsTwenty-nine articles met our inclusion criteria and were categorized into 3 groups as follows: (a) mobile versions of existing article or computerized neuropsychological tests; (b) new cognitive tests developed specifically for mobile platforms; and (c) the use of new types of data for cognitive assessment. This scoping review confirms the considerable potential of mobile assessment.Discussion and ImplicationsMobile technologies facilitate repeated and continuous assessment and support unobtrusive collection of auxiliary behavioral markers of cognitive impairment, thus allowing users to view trends and detect acute changes that have traditionally been difficult to identify. Opportunities include using new mobile sensors and wearable devices, improving reliability and validity of mobile assessments, determining appropriate clinical use of mobile assessment information, and incorporating person-centered assessment principles and digital phenotyping.

The Prison Letters of Demitrios Tsafendas, 1966–1986

This article focuses on a body of archival material on the imprisonment of Demitrios Tsafendas, the man who assassinated Hendrik Verwoerd, prime minister of South Africa from 1958 to 1966. At his Summary Trial in October 1966, Tsafendas was found to be insane and declared a ‘State President’s Patient’. He was incarcerated on Robben Island and in Pretoria Maximum Security prison between 1966 and 1994. During the course of my research on Tsafendas, I discovered a set of documents that dealt with the administrative, legal and medical details of his incarceration. Interspersed among the documents I found a number of letters written by Tsafendas between November 1966 and October 1986. These letters are significant for a number of reasons. They have never been used before, and very little of his prison life is covered in biographical accounts of his life, although he spent a total of 28 years in prison. Written over a period of roughly 20 years, these letters represent the only record of his attempt to ‘give an account of himself’. During this time, he was kept in solitary confinement and was not allowed access to newspapers, radio or television. Certain privileges that long-term prisoners had, such as permission to study, did not apply to him. Most of the letters were addressed to the prison authorities, requesting permission for certain medical treatments, study privileges, visitation rights and books such as dictionaries, encyclopedias and study materials. He also used these letters to express his opinions on a number of matters, which ranged from the quality of the clothing provided by the prison stores to German engineering feats during the Second World War. The wider national political context was one in which the apartheid regime experienced major political crises, and the imprint of these events are clearly discernible in the letters.

Gay Taboos in 1900 Brussels: The Literary, Journalistic and Private Debate Surrounding Georges Eekhoud's Novel Escal-Vigor

ABSTRACTGeorges Eekhoud was put on trial in October 1900, accused of depicting homosexuality in his 1899 novel Escal-Vigor. The trial engendered a unique series of events in Belgian contemporary public discourse: a debate on homosexuality in a country where such topics were usually completely ignored or condemned. Surprisingly, the debate that focused on the novel in newspapers was not entirely opposed to Eekhoud, who was finally acquitted in his trial. The publicity had an effect that was the opposite of what was hoped for by the authorities: Escal-Vigor went from obscurity to popularity, with six printings by 1901. A study of the public, private and literary debate surrounding the trial will allow us a glimpse of a brief moment in history where gay literature was at the centre of attention and ask ourselves what influence it had on the lot of homosexuals at the time.

Influence of long-term fertilization on soil physicochemical properties in a brown soil

This study aims to explore the influence on soil physicochemical properties under a 38-y long-term fertilization in a brown soil. Soil samples (0-20 cm)were taken from the six treatments of the long-term fertilization trial in October 2016:no fertilizer (CK), N1(mineral nitrogen fertilizer), N1P (mineral nitrogen and phosphate fertilizer), N1PK (mineral nitrogen, phosphate and potassic fertilizer), pig manure (M2), M2N1P (pig manure, mineral nitrogen and phosphate fertilizer).The results showed thatthe long-term application of chemical fertilizers reduced soil pH value, while the application of organic fertilizers increased pH value. Fertilization significantly increased the content of AHN, TN and SOM. Compared with the CK treatment and chemical fertilizer treatments, organic fertilizer treatments significantly increased the content of AP and TP. The content of AK and TK were no significant difference in different treatment.

Influence of Long-Term Fertilization on Spore Density and Colonization of Arbuscular Mycorrhizal Fungi in a Brown Soil

This study aims to explore changes of long-term fertilization on spore density and colonization of AMF (Arbuscular mycorrhizal fungi) under a 38-y long-term fertilization in a brown soil. Soil samples (0-20 cm,20-40cm,40-60cm)were taken from the six treatments of the long-term fertilization trial in October 2016:no fertilizer (CK), N1(mineral nitrogen fertilizer), N1P (mineral nitrogen and phosphate fertilizer), N1PK (mineral nitrogen, phosphate and potassic fertilizer), pig manure (M2), M2N1P (pig manure, mineral nitrogen andphosphate fertilizer).Spores were isolated from soils by wet sieving and sucrose density gradient centrifugation; mycorrhizal colonization levels were determined by the gridline intersect. The spore density was highest in the topsoils (0-20 cm), and was decreased with increasing of soil depth in each treatment. The spores density of M2N1P treatment was significantly higher than that of other treatments in each soil layer. Application of inorganic fertilizer (especially inorganic with organic fertilizer) can greatly improve the level of colonization. Our results suggested that long-term fertilization significantly affects spore density and colonization of AMF, however, spore density is not related to colonization rate.

Mental Health Community in Charleston Offers Services, Support in Wake of Violence

Mental Health Community in Charleston Offers Services, Support in Wake of Violence

Single dose vaccination of the ASO3-adjuvanted A(H1N1)pdm09 monovalent vaccine in health care workers elicits homologous and cross-reactive cellular and humoral responses to H1N1 strains

Healthcare workers (HCW) were prioritized for vaccination during the 2009 influenza A(H1N1)pdm09 pandemic. We conducted a clinical trial in October 2009 where 237 HCWs were immunized with a AS03-adjuvanted A(H1N1)pdm09 monovalent vaccine. In the current study, we analyzed the homologous and cross-reactive H1N1 humoral responses using prototype vaccine strains dating back to 1977 by the haemagglutinin inhibition (HI), single radial hemolysis SRH), antibody secreting cell (ASC) and memory B cell (MBC) assays. The cellular responses were assessed by interferon-γ (IFN-γ) ELISPOT and by intracellular staining (ICS) for the Th1 cytokines IFN-γ, interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). All assays were performed using blood samples obtained prior to (day 0) and 7, 14 and 21 d post-pandemic vaccination, except for ASC (day 7) and ICS (days 0 and 21). Vaccination elicited rapid HI, SRH and ASC responses against A(H1N1)pdm09 which cross reacted with seasonal H1N1 strains. MBC responses were detected against the homologous and seasonal H1N1 strains before vaccination and were boosted 2 weeks post-vaccination. An increase in cellular responses as determined by IFN-γ ELISPOT and ICS were observed 1–3 weeks after vaccination. Collectively, our data show that the AS03-adjuvanted A(H1N1)pdm09 vaccine induced rapid cellular and humoral responses against the vaccine strain and the response cross-reacted against prototype H1N1 strains dating back to 1977.

Exercise for cancer-related fatigue and putative functional, inflammatory, and metabolic mechanisms in patients receiving chemotherapy: A URCC CCOP research base phase III RCT.

TPS9651 Background: Up to 100% of cancer patients report cancer-related fatigue (CRF) during chemotherapy which co-occurs with impaired cardiopulmonary (CPF) and neuromuscular function (NMF), chronically up-regulated inflammatory responses, and low metabolic energy expenditure. CRF interferes with completion of treatment, increases cancer morbidity and mortality, and impairs quality of life (QOL). Exercise is one of the most promising treatments available for CRF, but no large multicenter phase III RCTs have confirmed these findings and little is known about the mechanisms through which exercise may impact CRF. Methods: We are conducting a nationwide multicenter phase III RCT (N=692) through the URCC CCOP Research Base with 23 CCOP affiliates. The primary aim is to determine if exercise will significantly improve CRF, and secondarily, CPF, NMF, inflammation, energy expenditure, and QOL compared to standard care in cancer patients receiving chemotherapy. The exercise intervention is our standardized, individually-tailored, home-based walking and progressive resistance program, “Exercise for Cancer Patients” (EXCAP, 7 days/wk, 6wks). To be eligible, patients must: 1) have a confirmed diagnosis of cancer with no leukemia or metastasis, 2) be chemotherapy naïve and scheduled to start, 3) not be receiving concurrent radiation, 4) have a KPS of >70, 5) be ≥21 years of age, 6) have no contraindications to exercise or functional testing, and 7) not be currently exercising. CRF and all secondary outcomes are assessed at baseline (pre-chemotherapy), 3 weeks (mid-intervention), and 6 weeks (post-intervention). Measures include: 1) CRF-Brief Fatigue Inventory, 2) CPF-6-minute walk test, 3) NMF-handgrip dynamometry, 4) inflammation-serum ELISA levels, 5) energy expenditure-actigraphy, and 6) quality of life-Functional Assessment of Chronic Illness Therapy. The DSMC reviewed the trial in October of 2012 and suggested it continue as planned. 532 participants have been enrolled in 36 months. Funding: NCI U10CA037420, U10CA37402-28, K07CA120025, K07CA132916, 1R25CA102618, ACS MRSG1300101CCE. Clinical trial information: NCT00924651.

Temozolomide for high grade glioma.

High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a novel oral chemotherapy drug that penetrates into the brain and purportedly has a low incidence of adverse events. To assess whether temozolomide has any advantage for treating HGG in either primary or recurrent disease settings. The following databases were searched: CENTRAL (Issue 10, 2012), MEDLINE, EMBASE, Science Citation Index, Physician Data Query and the Meta-Register of Controlled Trials in October, 2012. Reference lists of identified studies were searched. The Journal of Neuro-Oncology and Neuro-oncology were handsearched from 1999 to 2012 including conference abstracts. We contacted neuro-oncologists regarding ongoing and unpublished trials. Randomised controlled trials (RCTs) where the interventions were the use of temozolomide during primary therapy or for recurrent disease. Comparisons included no chemotherapy, non-temozolomide chemotherapy or different dosing schedules of temozolomide. Patients included those of all ages with histologically proven HGG. Two review authors undertook the quality assessment and data extraction. Outcome measures included: overall survival (OS); progression-free survival (PFS); quality of life (QoL); and adverse events. For primary therapy three RCTs were identified, enrolling a total of 745 patients, that investigated temozolomide in combination with radiotherapy versus radiotherapy alone for glioblastoma multiforme (GBM). Temozolomide increased OS (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.46 to 0.79, P value 0.0003) and increased PFS (HR 0.63, 95% CI 0.43 to 0.92, P value 0.02), when compared with radiotherapy alone, although these benefits only appear to emerge when therapy is given in both concomitant and adjuvant phases of treatment. A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications, fatigue and infections were increased with temozolomide.In recurrent HGG, two RCTs enrolling 672 patients in total found that temozolomide did not increase OS compared to standard chemotherapy (HR 0.9, 95% CI 0.76 to 1.06, P value 0.2) but it did increase PFS in a subgroup analysis of grade IV GBM tumours (HR 0.68, 95% CI 0.51 to 0.90, P value 0.008). Adverse events were similar between arms.In the elderly, 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone. QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide. Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone. It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events. In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression (TTP) and may have benefits on QoL without increasing adverse events but it does not improve overall. In the elderly, temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events.

TRANSGENIC BANANAS WITH ENHANCED RESISTANCE AGAINST XANTHOMONAS WILT DISEASE

Banana (Musa sp.) represents one of the most important world food crops after maize, rice, wheat and cassava. Many pests and diseases have significantly affected banana cultivation. Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum, is one of the most important diseases and currently considered as the biggest threat to banana production in the Great Lakes region of Africa including Uganda, Democratic Republic of Congo, Rwanda, Kenya, Tanzania and Burundi. The pathogen is highly contagious and its spread has endangered the livelihood of millions of farmers who rely on banana for food and income. The development of disease resistant bananas remains a high priority since farmers are reluctant to employ labor-intensive disease control measures and there is no host plant resistance among banana cultivars. The International Institute of Tropical Agriculture (IITA), in partnership with the National Agriculture Research Organization (NARO), Uganda and the African Agriculture Technology Foundation (AATF), have developed hundreds of transgenic bananas constitutively expressing the Hypersensitive Response Assisting Protein (Hrap) or Plant Ferredoxin Like Protein (Pflp) gene originated from sweet pepper (Capsicum annuum). These transgenic lines have exhibited strong resistance to BXW in the laboratory and screen house tests. The best 65 resistant lines were planted in a confined field trial in October 2010 at NARL, Kawanda, Uganda after approval from the National Biosafety Committee. This is a significant step toward development of transgenic banana cultivars resistant to BXW, which will boost the available arsenal to fight this epidemic disease and save livelihoods in Africa. These transgenic lines are under evaluation for disease resistance and agronomic performance in field conditions. This technology may also provide effective control to other bacterial diseases such as moko or blood disease of banana occurring in other parts of the world.

A(H1N1)pdm09 Vaccination of Health Care Workers: Improved Immune Responses in Low Responders Following Revaccination

We conducted a clinical trial in October 2009 to evaluate the immunogenicity of the AS03-adjuvanted influenza vaccine (pH1N1 vaccine) in health care workers (HCWs). By 2 weeks after vaccination, 97% had protective hemagglutinin inhibition (HI) titers (≥ 40) however, 16% were low responders (LR) and failed to maintain a protective response 90 days after vaccination. We analyzed the humoral responses (HI, antibody-secreting cell [ASC], and serum immunoglobulin G [IgG]) in 15 LRs and 25 control HCWs. Twelve LRs were revaccinated with the pH1N1 vaccine, and 7 were subsequently vaccinated with the 2010 seasonal trivalent influenza vaccine. We conducted a long-term analysis of the humoral and CD4(+) T-helper (Th) 1 responses. The LRs had a slower HI antibody response than the control HCWs, with protective antibody titers not reached until 2 weeks after vaccination in the majority of the participants. The LRs also had significantly lower IgG ASCs at day 7 and HA1-specific serum IgG responses at day 21, compared with the control HCWs. Revaccination with the pH1N1 vaccine elicited rapid HI antibody, ASC, memory B cell, and multifunctional CD4(+) Th1 cell responses. This study shows that revaccination of low-responding HCWs with the pH1N1 vaccine is required for maintaining long-term protection. NCT01003288.