Bernadette Coles | Cardiff University (original) (raw)

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Papers by Bernadette Coles

Cancer Treatment Reviews, 2009

s u m m a r y Background: Adjuvant hormone therapy (AHT) following radiotherapy or surgery is a t... more s u m m a r y Background: Adjuvant hormone therapy (AHT) following radiotherapy or surgery is a treatment option frequently offered to men with localised or locally advanced prostate cancer. We performed a systematic review of published randomised trials to assess the effectiveness of AHT. Methods: We searched MEDLINE, EMBASE, the Cochrane library, SCI, LILACS and SIGLE for randomised trials comparing AHT plus primary therapy (radiotherapy or prostatectomy) with primary therapy alone. Data on study design, participants interventions and outcomes were extracted from relevant studies and where possible pooled for meta-analysis. Findings: AHT following radiotherapy improved overall survival (at 5 years OR fixed effect model 1.29, 95% CI 1.07-1.56, p = 0.007), disease-specific survival (OR 2.10, 95% CI 1.53-2.88, p < 0.00001) and disease-free survival (OR 1.91, 95% CI 1.16-2.23, p < 0.00001). A random effect model favoured adjuvant hormone therapy but did not reach significance. After prostatectomy, there was no significant overall survival advantage with AHT, although one study reported a significant improvement in disease-specific survival (HR 4.09, p = 0.0004). Disease-free survival was also better with AHT (OR 3.73, 95% CI 2.30-6.03, p < 0.00001). AHT-induced toxicities included gynaecomastia, impotence, gastrointestinal and haematological. Conclusions: There are significant clinical benefits associated with the use of AHT for early prostate cancer. Patients should make an informed decision to accept AHT based on its effectiveness and side-effects.

Clinical Oncology

Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and the mesorectum are... more Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and the mesorectum are mobile structures and the use of image-guided radiotherapy techniques may improve treatment delivery. Studies up to 2008 have previously been reviewed; rectal motion was mostly studied in bladder and prostate cancer cases. Large variations were seen in both the rectal volume and rectal wall displacement during the treatment course. We reviewed the literature on primary rectal cancer. A systematic review was conducted using Medline and Embase databases using the keywords 'rectal, radiotherapy, IGRT, image guided, organ motion, internal margin, target shape/volume'. Nine studies looked at both inter-and intrafractional motion of the gross tumour volume, rectum, mesorectum and the clinical target volume using a variety of imaging modalities. There was significant movement in the upper mesorectum. There was a strong relationship between rectal filling and mesorectal motion. Differences according to gender and body mass index have been reported. One study showed adequate dose to the rectum despite rectal motion and deformation. Current margin recipes may not apply to deformable structures. Suggested margins for the clinical target volume to planning target volume expansion are between 1 and 3.5 cm. There may be a role for re-imaging and re-planning during a treatment course. From the available data, electronic portal imaging devices should continue to be used to match for bony anatomy. Additional information on internal motion can be obtained by cone beam computer tomography or tomotherapy and if available its use should be considered. Individualised anisotropic margins may be required. Further work is required to assess the optimal imaging modality, whether to match to bone or soft tissue, and to assess if internal motion affects treatment outcome.

Clinical Oncology

The global move towards more conformal radiotherapy for rectal cancer requires better imaging mod... more The global move towards more conformal radiotherapy for rectal cancer requires better imaging modalities that both visualise the disease accurately and are reproducible; to reduce interobserver variation. This review explores the advances in imaging modalities used in target volume delineation, with a view to make recommendations for current clinical practice and to propose future directions for research. A systematic review was conducted using MEDLINE and EMBASE. Articles considered relevant by the authors were included. Planning with orthogonal films is being replaced by computed tomography (CT) simulation. This is now considered the 'gold standard' and allows conformal three-dimensional planning. Magnetic resonance imaging (MRI) has been shown to overcome some of the limitations of CT and can be used either as a diagnostic image to visually aid planning, or as a 'planning' MRI carried out in the treatment position and co-registered with the planning CT. The latter approach has been shown to change the treated volumes compared with CT and in prostate cancer patients has been shown to reduce interobserver variation. There are remaining issues with four-dimensional motion that are yet to be fully appreciated or overcome. 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/CT co-registered with planning CT results in smaller volumes than CT alone and also reduces interobserver variation, but requires further validation before routine implementation. Experimental work utilising novel positron emission tomography tracers and diffusionweighted MRI shows promise and requires further evaluation. Rigorous quality assurance is important with processing of newer imaging modalities. Further work needs to be conducted into both interobserver variation and the formal evaluation of the clinical benefits of newer imaging modalities. Developments in imageguided radiotherapy are also required to ensure that improvements in target definition at the planning stage are reproducible throughout treatment.

Cancer Treatment Reviews, 2009

Background: This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for ... more Background: This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for the treatment of haemorrhoids.

Lancet Oncology, 2008

To cite this article: Agnelli G, Verso M. Management of venous thromboembolism in patients with c... more To cite this article: Agnelli G, Verso M. Management of venous thromboembolism in patients with cancer. J Thromb Haemost 2011; 9 (Suppl. 1): 316-324.

Bju International, 2004

To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical m... more To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium-to high-risk Ta and T1 bladder cancer.

Cancer, 2007

Men with clinically localized prostate cancer are faced with a wide range of treatment options, a... more Men with clinically localized prostate cancer are faced with a wide range of treatment options, and only Gleason grading is universally used as a histopathological prognostic factor for this disease. The significance of perineural invasion in diagnostic biopsies is controversial. Opinion about whether or not it should influence treatment decisions is currently almost equally divided. To address this, the authors performed a systematic review of studies that examine the association between perineural invasion and prostate cancer recurrence. MEDLINE, Embase, and the Web of Knowledge were searched from January 1990 to December 2005. Outcomes analyzed were the development of biochemical or clinical recurrence. Twenty-one articles on the association of perineural invasion in biopsies and prostate cancer recurrence after radical prostatectomy (n = 10) or radiotherapy (n = 11) were found but none on its significance in the context of watchful waiting. Structured data extraction was performed to allow comparisons between articles and to identify sources of heterogeneity to explain discrepancies in results. The considerable variation in study design, execution, and reporting precluded meta-analysis and quantitative risk estimation, but the weight of evidence suggested that perineural invasion in biopsies was a significant prognostic indicator, particularly in specific patient groups defined by presenting serum prostate-specific antigen levels and biopsy Gleason scores. Immediate treatment rather than watchful waiting may be more appropriate for patients with localized prostatic cancer and perineural invasion. However, the data are limited, and well-designed studies that use predefined stringent protocols are required to provide robust estimates of risk to aid in treatment planning. Cancer 2007. © 2006 American Cancer Society.

Bju International, 2001

Objective To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-... more Objective To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer.Patients and methods An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer.Results The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was −0.83 (95% confidence interval −0.57 to −1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21–0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported.Conclusion TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Lancet Oncology, 2007

The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent... more The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2.5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.

Cancer Treatment Reviews, 2009

s u m m a r y Background: Adjuvant hormone therapy (AHT) following radiotherapy or surgery is a t... more s u m m a r y Background: Adjuvant hormone therapy (AHT) following radiotherapy or surgery is a treatment option frequently offered to men with localised or locally advanced prostate cancer. We performed a systematic review of published randomised trials to assess the effectiveness of AHT. Methods: We searched MEDLINE, EMBASE, the Cochrane library, SCI, LILACS and SIGLE for randomised trials comparing AHT plus primary therapy (radiotherapy or prostatectomy) with primary therapy alone. Data on study design, participants interventions and outcomes were extracted from relevant studies and where possible pooled for meta-analysis. Findings: AHT following radiotherapy improved overall survival (at 5 years OR fixed effect model 1.29, 95% CI 1.07-1.56, p = 0.007), disease-specific survival (OR 2.10, 95% CI 1.53-2.88, p < 0.00001) and disease-free survival (OR 1.91, 95% CI 1.16-2.23, p < 0.00001). A random effect model favoured adjuvant hormone therapy but did not reach significance. After prostatectomy, there was no significant overall survival advantage with AHT, although one study reported a significant improvement in disease-specific survival (HR 4.09, p = 0.0004). Disease-free survival was also better with AHT (OR 3.73, 95% CI 2.30-6.03, p < 0.00001). AHT-induced toxicities included gynaecomastia, impotence, gastrointestinal and haematological. Conclusions: There are significant clinical benefits associated with the use of AHT for early prostate cancer. Patients should make an informed decision to accept AHT based on its effectiveness and side-effects.

Clinical Oncology

Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and the mesorectum are... more Radiotherapy for rectal cancer is becoming more conformal. Both the rectum and the mesorectum are mobile structures and the use of image-guided radiotherapy techniques may improve treatment delivery. Studies up to 2008 have previously been reviewed; rectal motion was mostly studied in bladder and prostate cancer cases. Large variations were seen in both the rectal volume and rectal wall displacement during the treatment course. We reviewed the literature on primary rectal cancer. A systematic review was conducted using Medline and Embase databases using the keywords 'rectal, radiotherapy, IGRT, image guided, organ motion, internal margin, target shape/volume'. Nine studies looked at both inter-and intrafractional motion of the gross tumour volume, rectum, mesorectum and the clinical target volume using a variety of imaging modalities. There was significant movement in the upper mesorectum. There was a strong relationship between rectal filling and mesorectal motion. Differences according to gender and body mass index have been reported. One study showed adequate dose to the rectum despite rectal motion and deformation. Current margin recipes may not apply to deformable structures. Suggested margins for the clinical target volume to planning target volume expansion are between 1 and 3.5 cm. There may be a role for re-imaging and re-planning during a treatment course. From the available data, electronic portal imaging devices should continue to be used to match for bony anatomy. Additional information on internal motion can be obtained by cone beam computer tomography or tomotherapy and if available its use should be considered. Individualised anisotropic margins may be required. Further work is required to assess the optimal imaging modality, whether to match to bone or soft tissue, and to assess if internal motion affects treatment outcome.

Clinical Oncology

The global move towards more conformal radiotherapy for rectal cancer requires better imaging mod... more The global move towards more conformal radiotherapy for rectal cancer requires better imaging modalities that both visualise the disease accurately and are reproducible; to reduce interobserver variation. This review explores the advances in imaging modalities used in target volume delineation, with a view to make recommendations for current clinical practice and to propose future directions for research. A systematic review was conducted using MEDLINE and EMBASE. Articles considered relevant by the authors were included. Planning with orthogonal films is being replaced by computed tomography (CT) simulation. This is now considered the 'gold standard' and allows conformal three-dimensional planning. Magnetic resonance imaging (MRI) has been shown to overcome some of the limitations of CT and can be used either as a diagnostic image to visually aid planning, or as a 'planning' MRI carried out in the treatment position and co-registered with the planning CT. The latter approach has been shown to change the treated volumes compared with CT and in prostate cancer patients has been shown to reduce interobserver variation. There are remaining issues with four-dimensional motion that are yet to be fully appreciated or overcome. 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/CT co-registered with planning CT results in smaller volumes than CT alone and also reduces interobserver variation, but requires further validation before routine implementation. Experimental work utilising novel positron emission tomography tracers and diffusionweighted MRI shows promise and requires further evaluation. Rigorous quality assurance is important with processing of newer imaging modalities. Further work needs to be conducted into both interobserver variation and the formal evaluation of the clinical benefits of newer imaging modalities. Developments in imageguided radiotherapy are also required to ensure that improvements in target definition at the planning stage are reproducible throughout treatment.

Cancer Treatment Reviews, 2009

Background: This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for ... more Background: This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for the treatment of haemorrhoids.

Lancet Oncology, 2008

To cite this article: Agnelli G, Verso M. Management of venous thromboembolism in patients with c... more To cite this article: Agnelli G, Verso M. Management of venous thromboembolism in patients with cancer. J Thromb Haemost 2011; 9 (Suppl. 1): 316-324.

Bju International, 2004

To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical m... more To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium-to high-risk Ta and T1 bladder cancer.

Cancer, 2007

Men with clinically localized prostate cancer are faced with a wide range of treatment options, a... more Men with clinically localized prostate cancer are faced with a wide range of treatment options, and only Gleason grading is universally used as a histopathological prognostic factor for this disease. The significance of perineural invasion in diagnostic biopsies is controversial. Opinion about whether or not it should influence treatment decisions is currently almost equally divided. To address this, the authors performed a systematic review of studies that examine the association between perineural invasion and prostate cancer recurrence. MEDLINE, Embase, and the Web of Knowledge were searched from January 1990 to December 2005. Outcomes analyzed were the development of biochemical or clinical recurrence. Twenty-one articles on the association of perineural invasion in biopsies and prostate cancer recurrence after radical prostatectomy (n = 10) or radiotherapy (n = 11) were found but none on its significance in the context of watchful waiting. Structured data extraction was performed to allow comparisons between articles and to identify sources of heterogeneity to explain discrepancies in results. The considerable variation in study design, execution, and reporting precluded meta-analysis and quantitative risk estimation, but the weight of evidence suggested that perineural invasion in biopsies was a significant prognostic indicator, particularly in specific patient groups defined by presenting serum prostate-specific antigen levels and biopsy Gleason scores. Immediate treatment rather than watchful waiting may be more appropriate for patients with localized prostatic cancer and perineural invasion. However, the data are limited, and well-designed studies that use predefined stringent protocols are required to provide robust estimates of risk to aid in treatment planning. Cancer 2007. © 2006 American Cancer Society.

Bju International, 2001

Objective To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-... more Objective To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer.Patients and methods An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer.Results The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was −0.83 (95% confidence interval −0.57 to −1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21–0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported.Conclusion TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Lancet Oncology, 2007

The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent... more The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2.5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.