Response to “Topical agent therapy for prevention and treatment of radiodermatitis : a meta-analysis”

To the Editor; It was with interest that I read the recent article by Zhang et al. published in Supportive Care in Cancer [1]. This paper highlighted the importance of radiodermatitis (RD) being an unresolved and distressing clinical issue in patients with cancer undergoing radiation therapy. However, I am concerned with a number of clinical and methodological issues within this paper: (i) the clinical and operational definition of prophylaxis and treatment of RD; (ii) the accuracy of the identification of trials; and (iii) the appropriateness of the conduct of the meta-analyses...

Upper-body morbidity after breast cancer : incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care

The purpose of this paper is to review the incidence of upper-body morbidity (arm and breast symptoms, impairments, and lymphedema), methods for diagnosis, and prevention and treatment strategies. It was also the purpose to highlight the evidence base for integration of prospective surveillance for upper-body morbidity within standard clinical care of women with breast cancer. Between 10% and 64% of women report upper-body symptoms between 6 months and 3 years after breast cancer, and approximately 20% develop lymphedema. Symptoms remain common into longer-term survivorship, and although lymphedema may be transient for some, those who present with mild lymphedema are at increased risk of developing moderate to severe lymphedema. The etiology of morbidity seems to be multifactorial, with the most consistent risk factors being those associated with extent of treatment. However, known risk factors cannot reliably distinguish between those who will and will not develop upper-body morbidity. Upper-body morbidity may be treatable with physical therapy. There is also evidence in support of integrating regular surveillance for upper-body morbidity into the routine care provided to women with breast cancer, with early diagnosis potentially contributing to more effective management and prevention of progression of these conditions.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

A natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer : a phase III double-blind randomised controlled trial

Purpose To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation induced skin reactions (RISR). Methods and Materials A total of 174 patients were randomised and participated in the study. Patients either received Cream 1 (the natural oil-based emulsion containing allantoin) or Cream 2 (aqueous cream). Skin toxicity, pain, itching and skin-related quality of life scores were collected for up to four weeks after radiation treatment. Results Patients who received Cream 1 had a significantly lower average level of Common Toxicity Criteria at week 3 (p<0.05), but had statistically higher average levels of skin toxicity at weeks 7, 8 and 9 (all p<0.001). Similar results were observed when skin toxicity was analysed by grades. With regards to pain, patients in the Cream 2 group had a significantly higher average level of worst pain (p<0.05) and itching (p=0.046) compared to the Cream 1 group at week 3, however these differences were not observed at other weeks. In addition, there was a strong trend for Cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison to Cream 1 (p=0.056). Overall, more participants in the Cream 1 group were required to use another topical treatment at weeks 8 (p=0.049) and 9 (p=0.01). Conclusion The natural oil-based emulsion containing allantoin appears to have similar effects for managing skin toxicity compared to aqueous cream up to week 5, however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream appears to be a more preferred option.

The prevention, detection and management of cancer treatment-induced cardiotoxicity: a meta-review

Background The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity. Methods Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses. Results One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality. Conclusion This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection and management of cancer treatment-associated cardiotoxicity. There is more evidence with respect to the prevention of this adverse effect of cancer treatment. This evidence, however, only applies to anthracycline-based chemotherapy in a predominantly adult population. There is no high-level evidence to guide clinical decision-making regarding the prevention, detection or management of radiation-induced cardiotoxicity.

Longitudinal patterns of weight in women diagnosed with breast cancer [Conference Abstract]

Introduction: Weight gain is a common concern following breast cancer and has been associated with negative health outcomes. As such, prevention of weight gain is of clinical interest. This work describes weight change between 6- and 18-months following a breast cancer diagnosis and explores the personal, treatment and behavioural characteristics associated with gains in weight. Methods: Body mass index was objectively assessed, at three-monthly intervals, on a population-based sample of women newly diagnosed with unilateral breast cancer (n=185). Changes in BMI between 6- and 18-months post-diagnosis were calculated, with gains of one or more being considered clinically detrimental to future health. Results: Approximately 60% of participants were overweight or obese at 6-months post-diagnosis. While BMI remained relatively stable across the testing period (range=27.3-27.8), 24% of participants experienced clinically relevant gains in BMI (median gains=1.9). Following adjustment for potential confounders, younger age (<45 years; Odds ratio, OR=9.8), being morbidly obese at baseline (OR=4.6) and receiving hormone therapy (OR=4.8) were characteristics associated with an increased odds (p<0.05) of gaining BMI. Other characteristics associated with gains in BMI were more extensive surgery and having a history of smoking, although these relationships were not supported statistically. In contrast, caring for younger children was associated with reduced risk of gaining BMI (OR=0.3, p=0.20). Conclusions: Clinically relevant weight gain between 6- and 18-months post-breast cancer diagnosis is an issue for one in four women, with certain subgroups being particularly susceptible. However, the majority of women diagnosed with breast cancer are overweight or obese and gains in body weight are common. Thus, interventions that address the importance of achieving and sustaining a healthy body weight, delivered to all women with breast cancer, may have greater public health impact than interventions targeting any specific breast cancer subgroup.

Clinical whole-body skin examination reduces the incidence of thick melanomas

Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence-based assessments do not recommend population screening. We aimed to assess whether clinical whole-body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). A population-based case-control study of all Queensland residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%) Whole-body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75mm) (OR= 0.86, 95% CI=0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76-1.49mm was reduced by 7% (OR=0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50-2.99mm (OR=0.83, 95% CI=0.65, 1.05) and by 40% for melanomas ≥3mm (OR=0.60, 95% CI=0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (≤0.75mm) (OR=1.38, 95% CI=1.22, 1.56). This is the strongest evidence to date that whole-body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.

Quality issues for the National Bowel Cancer Screening Program (NBCSP)

Purpose: This two-part research project was undertaken as part of the planning process by Queensland Health (QH), Cancer Screening Services Unit (CSSU), Queensland Bowel Cancer Screening Program (QBCSP), in partnership with the National Bowel Cancer Screening Program (NBCSP), to prepare for the implementation of the NBCSP in public sector colonoscopy services in QLD in late 2006. There was no prior information available on the quality of colonoscopy services in Queensland (QLD) and no prior studies that assessed the quality of colonoscopy training in Australia. Furthermore, the NBCSP was introduced without extra funding for colonoscopy service improvement or provision for increases in colonoscopic capacity resulting from the introduction of the NBCSP. The main purpose of the research was to record baseline data on colonoscopy referral and practice in QLD and current training in colonoscopy Australia-wide. It was undertaken from a quality improvement perspective. Implementation of the NBCSP requires that all aspects of the screening pathway, in particular colonoscopy services for the assessment of positive Faecal Occult Blood Tests (FOBTs), will be effective, efficient, equitable and evidence-based. This study examined two important aspects of the continuous quality improvement framework for the NBCSP as they relate to colonoscopy services: (1) evidence-based practice, and (2) quality of colonoscopy training. The Principal Investigator was employed as Senior Project Officer (Training) in the QBCSP during the conduct of this research project. Recommendations from this research have been used to inform the development and implementation of quality improvement initiatives for provision of colonoscopy in the NBCSP, its QLD counterpart the QBCSP and colonoscopy services in QLD, in general. Methods – Part 1 Chart audit of evidence-based practice: The research was undertaken in two parts from 2005-2007. The first part of this research comprised a retrospective chart audit of 1484 colonoscopy records (some 13% of all colonoscopies conducted in public sector facilities in the year 2005) in three QLD colonoscopy services. Whilst some 70% of colonoscopies are currently conducted in the private sector, only public sector colonoscopy facilities provided colonoscopies under the NBCSP. The aim of this study was to compare colonoscopy referral and practice with explicit criteria derived from the National Health & Medical Research Council (NHMRC) (1999) Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer, and describe the nature of variance with the guidelines. Symptomatic presentations were the most common indication for colonoscopy (60.9%). These comprised per rectal bleeding (31.0%), change of bowel habit (22.1%), abdominal pain (19.6%), iron deficiency anaemia (16.2%), inflammatory bowel disease (8.9%) and other symptoms (11.4%). Surveillance and follow-up colonoscopies accounted for approximately one-third of the remaining colonoscopy workload across sites. Gastroenterologists (GEs) performed relatively more colonoscopies per annum (59.9%) compared to general surgeons (GS) (24.1%), colorectal surgeons (CRS) (9.4%) and general physicians (GPs) (6.5%). Guideline compliance varied with the designation of the colonoscopist. Compliance was lower for CRS (62.9%) compared to GPs (76.0%), GEs (75.0%), GSs (70.9%, p<0.05). Compliance with guideline recommendations for colonoscopic surveillance for family history of colorectal cancer (23.9%), polyps (37.0%) and a past history of bowel cancer (42.7%), was by comparison significantly lower than for symptomatic presentations (94.4%), (p<0.001). Variation with guideline recommendations occurred more frequently for polyp surveillance (earlier than guidelines recommend, 47.9%) and follow-up for past history of bowel cancer (later than recommended, 61.7%, p<0.001). Bowel cancer cases detected at colonoscopy comprised 3.6% of all audited colonoscopies. Incomplete colonoscopies occurred in 4.3% of audited colonoscopies and were more common among women (76.6%). For all colonoscopies audited, the rate of incomplete colonoscopies for GEs was 1.6% (CI 0.9-2.6), GPs 2.0% (CI 0.6-7.2), GS 7.0% (CI 4.8-10.1) and CRS 16.4% (CI 11.2-23.5). 18.6% (n=55) of patients with a documented family history of bowel cancer had colonoscopy performed against guidelines recommendations (for general (category 1) population risk, for reasons of patient request or family history of polyps, rather than for high risk status for colorectal cancer). In general, family history was inadequately documented and subsequently applied to colonoscopy referral and practice. Methods - Part 2 Surveys of quality of colonoscopy training: The second part of the research consisted of Australia-wide anonymous, self-completed surveys of colonoscopy trainers and their trainees to ascertain their opinions on the current apprenticeship model of colonoscopy in Australia and to identify any training needs. Overall, 127 surveys were received from colonoscopy trainers (estimated response rate 30.2%). Approximately 50% of trainers agreed and 27% disagreed that current numbers of training places were adequate to maintain a skilled colonoscopy workforce in preparation for the NBCSP. Approximately 70% of trainers also supported UK-style colonoscopy training within dedicated accredited training centres using a variety of training approaches including simulation. A collaborative approach with the private sector was seen as beneficial by 65% of trainers. Non-gastroenterologists (non-GEs) were more likely than GEs to be of the opinion that simulators are beneficial for colonoscopy training (χ2-test = 5.55, P = 0.026). Approximately 60% of trainers considered that the current requirements for recognition of training in colonoscopy could be insufficient for trainees to gain competence and 80% of those indicated that ≥ 200 colonoscopies were needed. GEs (73.4%) were more likely than non-GEs (36.2%) to be of the opinion that the Conjoint Committee standard is insufficient to gain competence in colonoscopy (χ2-test = 16.97, P = 0.0001). The majority of trainers did not support training either nurses (73%) or GPs in colonoscopy (71%). Only 81 (estimated response rate 17.9%) surveys were received from GS trainees (72.1%), GE trainees (26.3%) and GP trainees (1.2%). The majority were males (75.9%), with a median age 32 years and who had trained in New South Wales (41.0%) or Victoria (30%). Overall, two-thirds (60.8%) of trainees indicated that they deemed the Conjoint Committee standard sufficient to gain competency in colonoscopy. Between specialties, 75.4% of GS trainees indicated that the Conjoint Committee standard for recognition of colonoscopy was sufficient to gain competence in colonoscopy compared to only 38.5% of GE trainees. Measures of competency assessed and recorded by trainees in logbooks centred mainly on caecal intubation (94.7-100%), complications (78.9-100%) and withdrawal time (51-76.2%). Trainees described limited access to colonoscopy training lists due to the time inefficiency of the apprenticeship model and perceived monopolisation of these by GEs and their trainees. Improvements to the current training model suggested by trainees included: more use of simulation, training tools, a United Kingdom (UK)-style training course, concentration on quality indicators, increased access to training lists, accreditation of trainers and interdisciplinary colonoscopy training. Implications for the NBCSP/QBCSP: The introduction of the NBCSP/QBCSP necessitates higher quality colonoscopy services if it is to achieve its ultimate goal of decreasing the incidence of morbidity and mortality associated with bowel cancer in Australia. This will be achieved under a new paradigm for colonoscopy training and implementation of evidence-based practice across the screening pathway and specifically targeting areas highlighted in this thesis. Recommendations for improvement of NBCSP/QBCSP effectiveness and efficiency include the following: 1. Implementation of NBCSP and QBCSP health promotion activities that target men, in particular, to increase FOBT screening uptake. 2. Improved colonoscopy training for trainees and refresher courses or retraining for existing proceduralists to improve completion rates (especially for female NBCSP/QBCSP participants), and polyp and adenoma detection and removal, including newer techniques to detect flat and depressed lesions. 3. Introduction of colonoscopy training initiatives for trainees that are aligned with NBCSP/QBCSP colonoscopy quality indicators, including measurement of training outcomes using objective quality indicators such as caecal intubation, withdrawal time, and adenoma detection rate. 4. Introduction of standardised, interdisciplinary colonoscopy training to reduce apparent differences between specialties with regard to compliance with guideline recommendations, completion rates, and quality of polypectomy. 5. Improved quality of colonoscopy training by adoption of a UK-style training program with centres of excellence, incorporating newer, more objective assessment methods, use of a variety of training tools such as simulation and rotations of trainees between metropolitan, rural, and public and private sector training facilities. 6. Incorporation of NHMRC guidelines into colonoscopy information systems to improve documentation, provide guideline recommendations at the point of care, use of gastroenterology nurse coordinators to facilitate compliance with guidelines and provision of guideline-based colonoscopy referral letters for GPs. 7. Provision of information and education about the NBCSP/QBCSP, bowel cancer risk factors, including family history and polyp surveillance guidelines, for participants, GPs and proceduralists. 8. Improved referral of NBCSP/QBCSP participants found to have a high-risk family history of bowel cancer to appropriate genetics services.

A systematic review of the association between physical activity and colorectal cancer risk

This review evaluated the strength of the evidence for a causal relationship between physical activity (PA) and colorectal cancer (CRC). A systematic review of databases through February 2008 was conducted to identify studies that assessed the association between total or recreational PA and incidence or mortality of CRC (including CRC, rectal cancer, colon cancer, and proximal or distal colon cancer). Studies were evaluated for significant associations between PA and risk of CRC endpoints and for evidence of dose–response relationships in the highest quality studies. Twenty cohort studies were evaluated; 11 were high-quality. Fifty percent of all studies and 64%of highest quality studies reported at least one significant association between PA and risk of a CRC endpoint (Po0.05).However, only 28%of all analyses (31% of analyses of highest quality studies) were significant (Po0.05). Only 40% of analyses of highest quality studies resulted in a significant P for trend (Po0.05); however, a non-significant inverse linear association between PA and colon cancer riskwas apparent.Heterogeneity in the evidence from all studies and from the highest quality studies was evident. Evidence from cohort studies is not sufficient to claim a convincing relationship exists between PA and CRC risk.

The hedgehog pathway inhibitor GDC-0449 shows potential in skin and other cancers

Background: The hedgehog signaling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer. Objectives/Methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer. Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subjects with medulloblastoma. GDC-0449 was well tolerated. Conclusions: Long term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway, in a wide range of solid tumours or not.