Showing papers by "Chris Parker published in 2022"

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5‐year follow‐up results from the STAMPEDE randomised trial (NCT00268476)

Abstract: Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long‐term hormone therapy for prostate cancer. This long‐term analysis in metastatic patients was planned for 3 years after the first results. Standard‐of‐care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC‐alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly‐diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow‐up, 329 SOC‐alone deaths (118 low‐risk, 178 high‐risk) and 244 SOC + AAP deaths (75 low‐risk, 145 high‐risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50‐0.71; P = 0.31 × 10−9) favoured SOC + AAP, with 5‐years survival improved from 41% SOC‐alone to 60% SOC + AAP. This was similar in low‐risk (HR = 0.55; 95% CI: 0.41‐0.76) and high‐risk (HR = 0.54; 95% CI: 0.43‐0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

Abstract: Background STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). Methods and findings Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. Conclusions Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. Trial registration ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

Docetaxel for Nonmetastatic Prostate Cancer: Long-Term Survival Outcomes in the STAMPEDE Randomized Controlled Trial

Abstract: Abstract Background STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. Methods Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). Results Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. Conclusions There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Imperata cylindrica (cogon grass).

Abstract: Abstract I. cylindrica is a serious weed not only in crops but also in natural areas, causing serious economic and environmental damage. The ability of I. cylindrica to effectively compete for water and nutrients, spread and persist through the production of seeds and rhizomes that can survive a wide range of environmental conditions, and its allelopathic effects and pyrogenic nature, allow it to exclude native plant species and other desirable plants and dominate large areas of land.

Phragmites australis (common reed).

Abstract: Abstract Phragmites australis, the common reed, is an aggressive, vigorous species which, in suitable habitats, will out-compete virtually all other species and form a totally dominant stand. Its invasive character has been particularly apparent in North America where it has become dominant in a range of wetland habitats replacing native species and biotypes including the native North American P. australis subsp. americanus. Bird, fish and insect populations can also be affected.

Standard and hypofractionated dose escalation to intraprostatic tumour nodules in localised prostate cancer: 5 year efficacy and toxicity in the DELINEATE trial.

Abstract: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy.DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years.Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C).The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.

Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer—Prevalence and Current Clinical Practice

Abstract: Aims Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT). Methods Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan–Meier method and log-rank test were used to calculate progression-free and overall survival. Results A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone. Conclusions In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators.

Mimosa pudica (sensitive plant).

Abstract: Abstract M. pudica is an annual or biannual sub-woody plant native to South America. It was introduced outside of its native range as an ornamental species, and is still available for sale today. This species is typically present in disturbed areas in much of the tropics where it has naturalized. It can be readily and accidentally dispersed thanks to its propagules that stick to mammals' hairs and human clothing. M. pudica can become extremely weedy in disturbed sites, often forming monotypic ground cover, and is a major weed of many tropical crops. It is classified as invasive in a wide range of countries in Asia and the Pacific and is regarded as an undesirable import in to Florida, USA and Australia (ISSG, 2017). It is also reported as invasive in Burundi, Kenya, Malawi, Tanzania and Uganda.

Euonymus japonicus (Japanese spindle tree).

Abstract: Abstract A datasheet on Euonymus japonicus covering, as an economically important tree, its taxonomy, importance, silviculture, distribution, biology and ecology, uses, products and pests.

Conium maculatum (poison hemlock)

Abstract: This datasheet on Conium maculatum covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Pluchea indica (Indian camphorweed)

Abstract: This datasheet on Pluchea indica covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Sphagneticola trilobata (wedelia).

Abstract: Abstract S. trilobata has spread rapidly threatening the native flora after introduction as an ornamental species. It can spread vegetatively and is difficult to eradicate. The IUCN has listed S. trilobata in its 100 of the world's worst invasive alien species and the Florida Exotic Plant Pest Council classified it as a category II invader. This species continues to be available as an ornamental and is therefore likely to spread further.

Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial

Abstract: Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3–5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). Conclusion An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings. ClinicalTrials.gov registration no. NCT01292291

Plantago coronopus (Buck's-horn plantain)

Abstract: This datasheet on Plantago coronopus covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Best Approaches and Updates for Prostate Cancer Biochemical Recurrence.

Abstract: Biochemical recurrence develops in almost one-third of men with prostate cancer after treatment with local therapy. There are numerous options for management, including surveillance, salvage radiation, androgen deprivation therapy (ADT), and clinical trials. This article reviews the current approaches to radiation therapy, ADT, and molecular imaging in men with biochemically recurrent prostate cancer. First, radiation therapy, including selection of field, dose, and use of concurrent antiandrogen therapy, is reviewed. Next, molecular imaging is addressed, including prostate-specific membrane antigen PET imaging and its increased sensitivity in identifying sites of disease. Finally, the factors associated with starting ADT are explored, and the data supporting intermittent over continuous ADT are reviewed. Lastly, the use of prostate-specific membrane antigen PET imaging and its potential role influencing therapy are discussed.

Portulaca quadrifida (chickenweed)

Abstract: This datasheet on Portulaca quadrifida covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Arthraxon hispidus (small carpetgrass)

Abstract: This datasheet on Arthraxon hispidus covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Further Information.

Orobanche cumana (sunflower broomrape).

Abstract: Abstract O. cumana is an obligatory, non-photosynthetic root parasite. It is believed to have evolved relatively recently from forms of O. cernua parasitizing wild Asteraceae, in particular species of Artemisia, and transferring to cultivated Helianthus annuus (sunflower). O. cumana is thought to be native to Eastern Europe (Russia) and has subsequently spread to most other sunflower growing regions of central and western Europe and Asia. The absence of O. cumana in sunflower growing regions of South America (for example Argentina) is believed to be associated with warmer winter temperatures not suitable for this species, rather than the seeds not being present. O. cumana can cause immense damage to cultivated sunflowers resulting in a significant decrease in yield. Despite resistant sunflower varieties being developed more virulent races of O. cumana have repeatedly evolved, or been selected, to overcome resistance. Thus, in spite of constant breeding efforts, losses continue in established sunflower growing areas and there is potential for it to invade new areas, wherever sunflower is grown.

Acanthospermum australe (spiny-bur)

Abstract: This datasheet on Acanthospermum australe covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Poa pratensis (smooth meadow-grass)

Abstract: This datasheet on Poa pratensis covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Lepidium latifolium (perennial pepperweed).

Abstract: Abstract L. latifolium is an erect, branching perennial native to southern Europe and western Asia. It was accidentally introduced into countries outside of its native range as a contaminant of seeds such as Beta vulgaris. L. latifolium exhibits a wide ecological adaptation to different environmental factors, tolerating a range of soil moisture and salinity conditions, which has allowed it to spread explosively in recent years in wetlands and riparian areas especially in the western USA. L. latifolium thrives in many lowland ecosystems and is extremely competitive, forming monospecific stands that can crowd out desirable native species and a number of threatened and endangered species. L. latifolium alters the ecosystem in which it grows, acting as a 'salt pump' which takes salt ions from deep in the soil profile and deposits them near the surface, thereby shifting plant composition and altering diversity.

Paspalum distichum (knotgrass).

Abstract: Abstract P. distichum is a fast-growing rhizomatous grass of wet areas. It has become a major weed of rice and many other crops, as well as occurring in uncropped wetlands in both its native and introduced regions. Its introduction to Europe, Asia and the Pacific is not well documented but apparently occurred many years ago. New records are reported in e.g. Indonesia, Spain and Croatia, suggesting that it continues to spread in countries to which it has been introduced.

Solanum viarum (tropical soda apple)

Abstract: This datasheet on Solanum viarum covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Leucanthemum vulgare (oxeye daisy)

Abstract: This datasheet on Leucanthemum vulgare covers Identity, Overview, Distribution, Dispersal, Hosts/Species Affected, Diagnosis, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.

Setaria verticillata (bristly foxtail).

Abstract: Abstract S. verticillata is listed by Holm et al. (1979) as a 'serious' or 'principal' weed in 11 countries in Europe, Asia, Africa, South America and the Pacific. From its origins in Europe and perhaps Africa, it has been accidentally introduced to many other countries across the world. It is often listed as one of the two or three most important weeds in a wide range of crops, within and outside its native range, and it can also become dominant in grassland. The combination of ready dispersal by its 'sticky' seed and seed-heads, and its C4 physiology and rapid growth make it an extremely successful invader. It adapts to local conditions rapidly and has developed resistance to atrazine and other herbicides.