Cancer

To the Editor: Cancer Voices NSW, a leading organisation for health care consumers, welcomes the coverage in the 18 April issue of the Medical Journal of Australia of gaps in and barriers to research endeavours into cancer. We particularly commend Olver’s editorial which, among other things, calls for more consumer-friendly clinical trial registries to play a role in enhancing patient recruitment by making it easier for them to find suitable trials.1 Cancer Voices NSW (http://www.cancervoices.org.au), the voice of people affected by cancer in our state, has long advocated for such a resource, both centralised and reliable. We are delighted to advise Journal readers that an initiative of ours, the Australian Cancer Trials website (http://www.australiancancertrials.gov.au), is now up and running. It has been publicly available since its launch by Professor Jim Bishop, Australia’s Chief Medical Officer, in November 2010 and is hosted by Cancer Australia. In partnership with consumers, the development of the project was led by a research team that included members from the University of Sydney, the Australian New Zealand Clinical Trials Registry (ANZCTR), Cancer Voices NSW and Cancer Australia. Consumers had considerable input to the website’s development through consultation with members of Cancer Voices NSW and Cancer Australia’s National Consumer Advisory Group. The Australian Cancer Trials website was funded by Cancer Australia with partial funding from the National Health and Medical Research Council project grant (grant reference number 512380). The Australian Cancer Trials website’s consumer-friendly portal offers open access information held on both the ANZCTR and the United States ClinicalTrials.gov registers (http://clinicaltrials.gov/). It currently lists over 1000 cancer trials, and it is updated every day. Consumers can do a “simple search” by cancer type or keyword or an “advanced search” using criteria including cancer status, trial focus, phase of clinical trial, recruitment status and age category. Information about each trial is displayed in a user-friendly format. All cancer trials registered with ANZCTR in Australia for which a few consumer-friendly additional cancer fields are completed at registration will find recruitment easier. Patients with cancer and their specialists will have much easier access to up-to-date clinical trial information. This website is a successful model that can be translated to other diseases and conditions, and indeed, generically.

Sally Crossing

Australia’s efforts to prevent, diagnose and treat cancer are not as successful for Aboriginal and Torres Strait Islander people as they are for other Australians. There is a need for a nationally coordinated, collaborative, priority-driven research effort to better understand what works, and we need to implement that knowledge. All aspects of the process must involve genuine Indigenous leadership and participation.

Gail Garvey BEd, MEd · Joan Cunningham ScD · Patricia C Valery PhD, MD, MPH · John Condon PhD · David Roder AM, MPH, DDSc · Ross Bailie MB ChB, FAFPHM · Jennifer Martin PhD, FRACP, GAICD · Ian Olver AM, FRACP

Australian and US collaborators provide evidence on outcomes of mammographic screening in previously affected women Women with a personal history of breast cancer (PHBC) represent an increasing group of cancer survivors, and have a lifelong increased risk of developing a new or recurrent cancer in the conserved (ipsilateral) breast, or a contralateral cancer. The risk of a “second” breast cancer in women with PHBC has been estimated at 5.4 to 6.6/1000 woman-years.1 Evidence of screening benefit in PHBC women comes from observational studies2-4 and extrapolation of benefit from randomised mammographic screening trials; consensus-based recommendations include annual mammography in routine surveillance of PHBC women.5-7 Early detection may also minimise the physical and psychosocial burden and consequences of a second breast cancer. Evidence reviews have consistently acknowledged the lack of quality data on mammographic screening in PHBC women,4,8 and research into screening high-risk women has mostly focused on those with breast and ovarian cancer susceptibility genes; evaluation of screening in women with PHBC has received relatively little attention.4,8 Together with other collaborators from Australia and the United States, we recently reported the most comprehensive study to date of mammographic screening in women with a history of early-stage breast cancer.9 Based on data from mammography facilities affiliated with the US National Cancer Institute-funded Breast Cancer Surveillance Consortium for the years 1996–2007, we examined the accuracy and outcomes of screening in 58 870 mammograms from 19 078 women with PHBC. These were matched to 58 870 screening mammograms from 55 315 women without PHBC, to ensure that characteristics that affect mammography accuracy (such as age group and breast density) were similar in both cohorts.9 Key findings from the study are summarised in the Box. Although the cancer detection rate of screening was substantially higher in PHBC women relative to women without PHBC (6.8 v 4.4/1000 screens), screening detected a smaller proportion of the cancers occurring in PHBC women at 1-year follow-up (65.4% v 76.5%). Due to this lower sensitivity of mammographic screening, as well as the higher underlying breast cancer risk in PHBC women, the interval cancer rate in women with PHBC was more than twice the rate in women without PHBC (3.6 v 1.4/1000 screens). The lower sensitivity and higher interval cancer rate occurred despite more imaging work-up in PHBC women relative to women without PHBC (18.1% v 8.3%) and more recommendations for biopsy or surgical consultation (2.3% v 1.4%). Unique aspects of this study were characterisation of screening outcomes and underlying cancer risk according to characteristics of the women and their first cancer treatment, and ascertainment of ipsilateral and contralateral second cancers.9 The latter has not previously been possible because notification of recurrent cancer is not obligatory in most countries, but was achieved through the data-linkage processes of the Breast Cancer Surveillance Consortium. Hence, the twofold higher rate of breast cancer in women with PHBC relative to those without (Box) represents a reliable risk estimate. We found heterogeneity of both breast cancer risk and screening accuracy across subgroups of women and by the treatment received for the first cancer. The highest rates of second cancers (> 12 cancers/1000 screens) were in women younger than 50 years, women with extremely dense breasts, women who received breast-conserving surgery without radiation therapy or who did not receive any systemic therapy, and women with previous ductal carcinoma-in-situ (the latter probably reflects the infrequent use of adjuvant therapy in the treatment of ductal carcinoma-in-situ). Should these findings change our practice or recommendations for women with PHBC? Superficially, these results9 could be interpreted as casting doubt on the efficacy of mammographic screening in women with PHBC. However, careful consideration of the data shows that although mammographic screening was relatively less sensitive in PHBC women, it detected their second cancers at an early stage, with similar stage distributions to women without PHBC.9 The evidence from this study therefore supports consensus recommendations that advise mammographic screening in women with PHBC, and which also include clinical breast examination as part of annual surveillance.5-7 Many of the interval cancers were also early-stage, suggesting that cancers not detected at time of mammographic screening were detected through clinical examination or investigations prompted by symptoms, or possibly through ad-hoc adjunct screening (using breast ultrasound or magnetic resonance imaging). Currently, adjunct screening is not routinely recommended for women with PHBC (unless they are known to have breast cancer gene mutations), and our study did not evaluate adjunct imaging. Our data may, however, guide future evaluations of adjunct screening in subgroups of PHBC women who had high interval cancer rates; specifically, women younger than 50 years and/or with extremely dense breasts, and those who had breast conservation without radiation therapy for their first cancer. It is essential that evaluations of strategies integrating adjunct screening for PHBC women consider the impact this may have on false positives and overdetection, as well as whether enhanced screening sensitivity through adjunct imaging translates into a reduction in interval cancers. Recommendations from the BreastScreen Australia evaluation10 included the potential provision of annual screening through BreastScreen for women with PHBC, from 5 years after their first cancer diagnosis. Our study shows that screening sensitivity improves after 5 years from the first cancer diagnosis and supports the idea of allowing PHBC women access to screening in BreastScreen-accredited facilities, which undergo rigorous quality assurance, to ensure that they receive high-quality mammographic screening. BreastScreen may also be ideally placed to implement screening evaluations for PHBC women to provide insight into screening outcomes in these women in the Australian setting. Mammographic screening in women with a personal history of early-stage breast cancer (PHBC)9* Screening outcomes were significantly different (P < 0.001) for comparison of screening mammograms in women with PHBC relative to women without PHBC: Cancer rate: 10.5 (9.7–11.3) v 5.8 (5.2–6.4)/1000 screens Cancer detection rate: 6.8 (6.2–7.5) v 4.4 (3.9–5.0)/1000 screens Interval cancer rate: 3.6 (3.2–4.1) v 1.4 (1.1–1.7)/1000 screens Screening sensitivity: 65.4% (61.5%–69.0%) v 76.5% (71.7%–80.7%) Sensitivity for detection of invasive cancers: 61.1% (56.6%–65.4%) v 75.7% (70.4%–80.3%) Screening specificity: 98.3% (98.2%–98.4%) v 99.0% (98.9%–99.1%) Abnormal mammogram results (based on final imaging assessment): 2.3% (2.2%–2.5%) v 1.4% (1.3%–1.5%); this also reflects the percentages recommended for biopsy or surgical consultation. Screen-detected breast cancers in women with and without PHBC were predominantly early-stage cancers (ductal carcinoma-in-situ [DCIS] or stage I–II invasive cancer in > 90%, for both groups). In women with PHBC, screening sensitivity was similar for detection of ipsilateral cancer (66.3% [60.3%–71.8%])† and contralateral cancer (66.1% [60.9%–70.9%]); however, sensitivity differed significantly (P < 0.05) for the following: Higher for detection of DCIS (78.7% [71.4%–84.5%]) than invasive cancer (61.1% [56.6%–65.4%]) Higher in women with non-dense breasts (BI-RADS category 1–2: 69.6% [63.3%–75.3%]) than in women with dense breasts (BI-RADS category 3–4: 60.2% [54.0%–66.2%])‡ Higher after 5 years from first cancer (70.8% [65.4%–75.6%]) than within the initial 5 years (60.2% [54.7%–65.5%]) Lower in women who received any systemic therapy§ (54.1% [47.5%–60.6%]) than in those who had not received any systemic therapy (71.0% [66.0%–75.5%]) for first cancer. Low screening sensitivity (about 55% or lower) was observed in women younger than 50 years, women with extremely dense breasts, and women who received chemotherapy§ for first cancer. BI-RADS = Breast Imaging Reporting and Data System. * 95% confidence intervals are shown in parentheses. † Excludes ipsilateral relapse in women who had mastectomy. ‡ BI-RADS tissue density categories: 1 = almost entirely fatty; 2 = scattered fibroglandular tissue; 3 = heterogeneously dense; 4 = extremely dense. § After adjusting for age, breast density, stage and treatment of first cancer, only women who received chemotherapy were significantly less likely to have their second breast cancer detected by mammographic screening than women who had not received any systemic therapy.

Nehmat Houssami MB BS, FAFPHM, PhD · Diana L Miglioretti PhD

Upcoming large studies may shed light on why this technique was not rapidly widely adopted like certain other laparoscopically assisted procedures Laparoscopic “keyhole” surgery has been the gold standard for gall bladder surgery for a few decades. It has also been widely used for appendicectomies, a multitude of gynaecological procedures and, to various extents, for other procedures such as hernia repair, splenectomy and nephrectomy. However, the uptake of laparoscopically assisted resection in elective surgery for colorectal cancer (CRC) has been slow, both in Australia and overseas. This is the subject of the article by Thompson and colleagues in this issue of the Journal (→ National trends in the uptake of laparoscopic resection for colorectal cancer, 2000–2008).1 The authors searched the National Hospital Morbidity Database (NHMD), which uses codes based on Medicare Benefits Schedule item numbers, for elective laparoscopic resections for CRC. Their search was somewhat restricted and the internal validity was not tested, but Thompson and colleagues reported that, in about a quarter of elective CRC resections performed in Australia in the financial year 2007–08, an item number for a laparoscopy was included. Reliance on databases may overestimate or underestimate outcomes. Three studies from the United States reported percentages of laparoscopic resections for cancers of the colon ranging from 3.3% to 5.2%2-4 in the period July 2003 to June 2004, based on the National Cancer Data Base and Nationwide Inpatient Sample. However, a fourth US study that used the Perspective Rx Comparative Database (Premier Inc, Charlotte, NC), which relies on procedure codes, reported a percentage of 33.7% for the period July 2004 to June 2006.5 Such an increase is far greater than what would be expected to be the result of the publication of the Clinical Outcomes of Surgical Therapy trial.6 The adoption of laparoscopic surgery for CRC has been slow despite the proven short-term benefits of laparoscopic compared with open resection, which include a shorter hospital stay.7,8 In line with other published articles, the Australasian Laparoscopic Colon Cancer Study (ALCCaS) — the largest Australasian study to date of laparoscopic resection for CRC — showed that the laparoscopic method was associated with a smaller number of patients with complications and a shorter length of stay than open resection.9 However, the ALCCaS group also reported that reviews show that the short-term advantages for laparoscopic resection for CRC are arguably relatively minor and often subjective, and that patients who benefit most from improved outcomes are patients who are aged 70 years or older whose procedures were completed laparoscopically.10 The median length of stay for patients younger than 70 years of age undergoing laparoscopic resection in the ALCCaS trial was 7 days (range, 1–30 days) compared with 8 days (range, 4–49 days) for open resections in the same age group — a difference of only 1 day.10 The average hospital stay for conventional open resection has been reported to be about 10 days (range, 7–12 days).7,11-13 It seems likely that authors of large series, trials and reviews report more conservative (and perhaps more realistic) results than earlier series reporting a new surgical procedure or innovation. The first published series of laparoscopic colorectal surgery in 1991 reported achieving the aim of a 5-day hospital stay in 14 out of 20 patients undergoing sigmoid resections (70%).14 Most subsequent larger studies, reviews and meta-analyses report lengths of stay of around 8 days for laparoscopic resection.7-9,11,12 Thompson and colleagues (→ National trends in the uptake of laparoscopic resection for colorectal cancer, 2000–2008) recommend exploring whether the short-term benefits of laparoscopic resection are experienced outside of the clinical trial environment.1 If we accept the limitation of using secondary data, such as those from the NHMD, in exploring the uptake of laparoscopic surgery for CRC, then a quarter of elective resections for CRC performed in Australia in 2007–08 were laparoscopic. That represents an increase from zero to 25% in more than 17 years. There are no comparable studies that used similar methods to assess the uptake of laparoscopic cholecystectomy in the late 1980s. However, many of us experienced first-hand the rapid uptake of laparoscopic gall bladder surgery. The first laparoscopic cholecystectomy was probably performed in France by Phillippe Mouriat of Lyons in 1987.15 There are published data that show that laparoscopic surgery was well and truly the gold standard for gall bladder surgery in 1992.16 That represents an increase from zero to close to 100% in less than 5 years. The contrast is stark. In 1999, Kehlet and Mogensen introduced the concept of fast-track surgery to colorectal resections;17 this concept is now known as Enhanced Recovery After Surgery (ERAS). It involves a multimodal rehabilitation program that commences before surgery to optimise all aspects of care using evidence-based protocols that hasten recovery. Kehlet and Mogensen reported a median hospital stay of 2 days (range, 2–6 days) after 16 consecutive elective open sigmoid colectomies. Fifteen of the 16 patients resumed bowel function before discharge.17 The results of a systematic review of five studies comparing laparoscopic with open colorectal surgery using an ERAS rehabilitation program were inconclusive.18 Further, the authors of a meta-analysis of 11 studies (1021 patients) reported a 2.5-day shorter length of stay for patients on an ERAS rehabilitation program who had resections compared with those not on an ERAS program.19 These authors assumed an added benefit to the laparoscopic approach, but an advantage was not clearly demonstrated. They concluded that ERAS programs should become a mainstay of elective colorectal surgery.19 These later and larger series, trials and reviews have shown that an average length of stay of 5 days seems to be quite achievable within an ERAS protocol, regardless of whether the surgical approach is open or laparoscopic. Many of the aspects of the ERAS program are now included in “standard” care regardless of whether a structured protocol is in place or not. It seems that, on the whole, laparoscopic surgery for CRC has probably not been successful in delivering the outstanding benefits suggested by early reports. This may be partly responsible for its slow uptake. Attention to a multimodal approach such as an ERAS program may, in fact, produce more clinical benefits for patients and cost benefits for hospitals. Whether the laparoscopic approach “adds” to these benefits or not has not been established.20 The Australasian Laparoscopic Cancer of the Rectum Trial (A La CaRT), with a target sample size of 470 patients, is expected to shed more light on the safety and efficacy of laparoscopic compared with conventional open resection for rectal cancer.21 The Dutch Laparoscopy and/or Fast Track Multimodal Management (LAFA) trial, with a target sample size of 400 patients, will examine laparoscopic versus open CRC surgery with or without an ERAS rehabilitation program.22

Ned S Abraham MMed, FRACS, PhD

Objective: To examine the trends in the uptake of laparoscopic resection for colorectal cancer.Design and setting: Retrospective analysis of Australia-wide data on elective resections for colorectal cancer over the 8 financial years 2000–01 to 2007–08, obtained from the National Hospital Morbidity Database.Main outcome measures: National trends in annual percentage of colorectal resections for cancer that were conducted laparoscopically for each year, stratified by hospitals conducting a high volume of elective resections (40 or more/year) versus a low volume, and by public versus private hospitals.Results: For all Australian hospitals combined, the percentage of resections for colon cancer conducted laparoscopically increased from 2.4% in 2000–01 to 27.5% in 2007–08. For rectal cancer, this increase was from 1.1% to 21.5%. The largest increases were seen in high-volume private hospitals (colon cancer, 2.7% to 34.1%; rectal cancer, 1.5% to 26.2%), but increases also occurred in high-volume public hospitals (colon cancer, 2.7% to 32.2%; rectal cancer, 0.5% to 20.3%), low-volume private (colon cancer, 3.8% to 27.1%; rectal cancer, 2.4% to 25.5%) and low-volume public (colon cancer, 1.1% to 17.0%; rectal cancer, 0.5% to 13.8%) hospitals.Conclusions: The use of laparoscopic resection for colorectal cancer has increased throughout Australian hospitals. Our findings provide the data necessary to ensure adequate resource allocation by the appropriate medical bodies to achieve optimal success in the uptake of laparoscopic resection for colorectal cancer in Australia.

Bridie S Thompson BSc · Michael D Coory BSc(Applied), MB BS, PhD · John W Lumley MB BS, FRACS

The Cancer Council Australia (CCA) Alcohol Working Group has prepared a position statement on alcohol use and cancer. The statement has been reviewed by external experts and endorsed by the CCA Board. Alcohol use is a cause of cancer. Any level of alcohol consumption increases the risk of developing an alcohol-related cancer; the level of risk increases in line with the level of consumption. It is estimated that 5070 cases of cancer (or 5% of all cancers) are attributable to long-term chronic use of alcohol each year in Australia. Together, smoking and alcohol have a synergistic effect on cancer risk, meaning the combined effects of use are significantly greater than the sum of individual risks. Alcohol use may contribute to weight (fat) gain, and greater body fatness is a convincing cause of cancers of the oesophagus, pancreas, bowel, endometrium, kidney and breast (in postmenopausal women). The existing evidence does not justify the promotion of alcohol use to prevent coronary heart disease, as the previously reported role of alcohol in reducing heart disease risk in light-to-moderate drinkers appears to have been overestimated. CCA recommends that to reduce their risk of cancer, people limit their consumption of alcohol, or better still avoid alcohol altogether. For individuals who choose to drink alcohol, CCA recommends that they drink only within the National Health and Medical Research Council guidelines for alcohol consumption.

Margaret H Winstanley BA · Iain S Pratt GradDip(Diet), APD, AEP · Kathryn Chapman BSc, MNutrDiet · Hayley J Griffin BMedSc, MNutrDiet, PhD · Emma J Croager PhD, MBA · Ian N Olver MD, PhD, FRACP · Craig Sinclair MPubPolMgt, GradDipOrgBehav, BEd(Sec) · Terry J Slevin MPH, FPHAA

Two contributions to this issue of the Journal indicate that there is a significant disparity between the research being undertaken in this country and the burden of disease we actually experience. These articles raise important issues about the guidance, funding and facilitation of research. Dear and colleagues (→ Landscape of cancer clinical trials in Australia: using trial registries to guide future research) report that there is a mismatch between the clinical burden of different cancers and the number of trials dedicated to studying them. Specifically, breast cancer is overrepresented in clinical trial activity, while other cancers including lung, colorectal, prostate and pancreatic cancers are underrepresented. Industry sources sponsor 43% of all trials (and 64% of drug trials), with a pronounced tendency toward involvement with randomised controlled trials of systemic interventions (drugs or biological agents) for patients with advanced (metastatic) disease. In an accompanying editorial, Olver (→ Cancer clinical trials in Australia) points out that this is a worldwide trend that at least partly reflects the pressure for pharmaceutical companies to study treatments that stand a good chance of showing a benefit in the relatively short term (eg, increasing life expectancy for a patient with advanced cancer), which can be readily translated into a marketable intervention. Other factors, such as the impact of consumer sentiment, may also have a significant influence on the number of trials funded in specific fields — breast cancer treatment, for example. Olver discusses the need to reverse the declining level of clinical trial activity in Australia and to better target clinical trials to the burden of disease in the community. Widespread participation in clinical research, by patients and doctors, should be fundamental to the practice of medicine in Australia (MJA 2011; 194: 59-60) — it is considered increasingly important in undergraduate and postgraduate training and is a requirement for academic advancement. While it is vital to learn research methodology, there is a central issue that should be addressed before commencing trial planning: Is the study needed? Clinical trial registries were established in 2005 in an attempt to eliminate publication bias towards studies with positive results (MJA 2004; 181: 293-294). The articles by Dear et al and Olver indicate that there is also a potential role for these registries in guiding the direction of research in our community. This suggests the need for a body to ease the difficult task of coordinating research groups and funders so that available research funds are spent optimally. As an example of this, the National Cancer Institute in the United States is planning to create a “cross-disease panel” that will establish priorities for funding and coordination of clinical trials. Pharmaceutical industry investment in clinical trials in Australia is important, but it needs to be more adequately complemented by appropriate investment from the public sector to support independent trial groups, hospital-based research and trials that improve care but which may not translate into marketable interventions.

Annette G Katelaris MB BS, MPH, FRACGP

Using registry data to identify gaps in research and enhance our clinical trial activity The data collected by clinical trial registries have many applications. Clinicians and patients can search for trial options for specific conditions when standard treatments have been exhausted, or where no effective treatment exists. Comparisons between trials registered and those subsequently reported can suggest publication bias. Researchers planning new trials can avoid duplication by identifying gaps in the targeting of cancer types in current trials. In this issue of the Journal (→ Landscape of cancer clinical trials in Australia: using trial registries to guide future research), Dear and colleagues have analysed data from the Australian New Zealand Clinical Trials Registry and an international registry based in the United States, ClinicalTrials.gov, to describe the landscape and funding sources of cancer trials in Australia, to aid the planning of future cancer trials.1 They found that the Australian situation reflects the international situation, where investment in trials for specific cancer types does not correlate with the disease burden caused by those cancers. For example, breast cancer accounted for 17% of trials, with high levels of patient recruitment, while lung cancer represented only 7% of trials despite its higher disease burden. The authors concede that this observation from the registry data may be inaccurate because registration of trials is not mandatory in Australia, and there is no way of recording the nature of unregistered trials. Also, the registries more comprehensively list Phase III trials than early phase trials, so overrepresentation of some tumour types could partly reflect more success in identifying potentially effective new drugs to treat them, which then progress to Phase III trials. If such disparities in research do exist, one remedy is targeted funding to attract research on different tumour types. Similarly, some types of tumour receive more popular exposure in the media than is warranted by their burden of disease, which allows speculation about the impact of consumers on the research agenda.2 This was postulated from the high number of non-drug intervention, non-industry-sponsored trials for breast cancer compared with other tumour types.1 It is also clear from the trial registries that non-drug trials, such as psychosocial trials, are generally underrepresented. These will rarely be funded by industry and require investment from government and community research funds. The importance of pharmaceutical industry sponsorship to the cancer clinical trial effort in Australia is underpinned by the finding that 64% of drug trials are funded by industry. It is not unexpected that industry was found to predominantly sponsor drug trials involving metastatic disease, where therapeutic gains can be more promptly translated into commercial success. Adjuvant trials are often multinational and, because survival is often the endpoint, take many years to achieve a result, unless an earlier surrogate endpoint can be identified. It is surprising that tumour type was not found to correlate with pharmaceutical industry sponsorship, as more trials involving higher-incidence tumours would have been anticipated. But the finding that systemic therapies attracted more industry sponsorship than local therapies was expected, as most sponsored studies would have new drug development as their goal. With the increasing development of targeted therapies, the histological type of cancer will become less important, but it remains a potential concern that financial incentives favour drug development for high-incidence tumours and that progress in treating rarer cancers is delayed. The registry data can provide a guide as to where future trial funding should be directed. An additional issue of great concern that may be reflected by clinical trial registries is a decrease in clinical drug trials being conducted in Australia.3,4 Clinical trials are essential to developing the evidence base for improving cancer treatments, and traditionally Australia has had a high trial recruitment rate relative to its population.4 A robust clinical trial program fosters and retains local expertise in scientific and medical research and clinical care. It also ensures the opportunity of early access to new treatments and improved quality of care and monitoring for patients participating in clinical trials, which enables translation into improved routine care and outcomes.5,6 There are also economic benefits of clinical trials: the average dollar invested in health research and development returns $2.17 in health benefits, and sponsored trials of new drugs serve to reduce a hospital’s drug expenditure.5 What is required to enhance clinical trial activity in Australia is to both support independent cooperative trial groups and encourage increased pharmaceutical industry investment. Infrastructure funding for trial groups, such as that provided by Cancer Australia, is vital, but hospitals must also see support of clinical research as a core part of their business rather than a source of additional revenue through facilities fees, which increasingly make trials more expensive to perform. E-health platforms will also enhance trial capabilities by centralising data for easier access and sharing, and making verification of source data easier.7 Clinical trial registries that are more consumer-friendly should play a role in enhancing patient recruitment by making it easier for them to find suitable trials. Centralising ethical review of multicentre trials, as is encouraged by the Australian Government’s Harmonisation of Multi-centre Ethical Review (HoMER) initiative, will streamline the ethics approval process, particularly for Phase III trials, without compromising the rigour of the review.8 Similarly, as part of the HoMER intiative, setting standards for the quality and timeliness of governance review of trials, which still must be done by individual health units, will also help facilitate the approval process. Data from clinical trial registries should be used to monitor the progress of such efforts to ensure Australia has a robust clinical trial capability.

Ian N Olver MD, PhD, FRACP

Objective: To quantify and describe current cancer clinical trial activity in Australia and help guide future trials research using trial registries.Design and setting: Data from cancer trials recruiting in Australia at 31 March 2009 were extracted from the Australian New Zealand Clinical Trials Registry and ClinicalTrials.gov. A regression model was used to identify factors associated with industry sponsorship.Main outcome measures: The proportion of cancer trials compared with estimated burden of disease for each cancer.Results: There were 368 interventional cancer trials open to recruitment. The most-researched cancer was breast cancer, accounting for 17% of trials. Only 7% of trials were in lung cancer, yet lung cancer is responsible for the greatest burden of disease. Industry was the primary sponsor in 43% of trials. Drug treatments were tested in most trials (69%). Trials were more likely to be industry sponsored if they tested systemic rather than local treatments (OR, 16.71; 95% CI, 4.70–59.43), included patients with advanced rather than early disease (OR, 3.76; 95% CI, 1.78–7.94) and used random rather than non-random allocation (OR, 1.78; 95% CI, 1.06–3.00).Conclusion: There is variation in the number of trials according to cancer site, with some cancers being underrepresented relative to their burden of disease. Industry sponsorship is more likely for trials that investigate systemic therapy, recruit patients with advanced disease and are randomised.

Rachel F Dear MB BS, FRACP · Alexandra L Barratt MB BS, MPH, PhD · Kevin McGeechan BSc, MBiostatistics · Lisa Askie PhD, MPH · John Simes MD, FRACP · Martin H N Tattersall MD, MSc, FRACP

Breast cancer: taking control. John Boyages. Sydney: Boycare Publishing, 2010. (367 pp, $39.99). ISBN 978098063111. RIGHT FROM when you first pick up this book, it captures your attention — starting with a cover that pictures a delightful old tree supporting a woman gazing into the distance. The author, Professor John Boyages, an oncologist with nearly 30 years’ experience treating the disease, uses a gardening analogy to introduce a very tough subject. His aim is to enable patients and their families to understand the experience of having a diagnosis of breast cancer and to take control of its management. Key information is explained in a direct and easy manner that addresses the anxiety and shock experienced in this situation. Boyages takes the reader through the different parts of “the garden” and the decisions that need to be made for gaining the best outcomes. He continues to use the gardening metaphor to describe medical pathology and techniques, thus simplifying information that could otherwise be overwhelming. The book has a practical design. Its 20 “control points”, or important steps or decisions, are divided into three parts according to the phases of treatment, and I felt like I was referring to a trusty roadmap or GPS (global positioning system) that would help me to reach my destination safely. Colour coding the key control points as “red for stop”, “amber for caution” and “green for proceed with care” makes it easier for readers to understand the treatment options and decision-making process. The use of real-life stories enables the reader to relate to these experiences. All the explanations are evidence-based and well referenced, to help patients make informed choices. Although this book is primarily for women and men diagnosed with breast cancer, and their families and friends, it is also a valuable resource for health professionals. It is well illustrated and includes over 75 web links, 20 flowcharts and 96 figures, which make it an easy read. I would recommend it to anyone involved with breast cancer or interested in learning more about it.

Elaine Arnold

Objective: To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines.Design and setting: We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 μg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31–60 min, or > 60 min.Main outcome measure: Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis.Results: Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure.Conclusion: There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency.

Kellie L Stalgis-Bilinski BSc, MNutrDiet, APD · John Boyages MB BS(Hons), FRACR, PhD · Elizabeth L Salisbury MB BS(Hons), FRCPA, FFOP · Colin R Dunstan PhD(Med), MSc, BSc(Hons) · Stuart I Henderson BSc, PhD(Applied Physics) · Peter L Talbot BSc, PostgradDipNutrDiet, MSc

CorrectionIncorrect confidence intervals: In “When do I know I am cured? Using conditional estimates to provide better information about cancer survival prospects” in the 17 January 2011 issue of the Journal (Med J Aust 2011; 194: 73-77), there were several minor errors in the 95% confidence intervals given in Box 1: Conditional 5-year relative survival estimates, by type of cancer and number of years after diagnosis, for patients aged 15–89 years at diagnosis, Queensland 1998–2007. These errors applied to survival estimates for stomach cancer, pancreatic cancer, lung cancer, kidney cancer, bladder cancer, non-Hodgkin lymphoma and leukaemia. The 95% CIs have been corrected in the online version of the article, and can be seen at: http://www.mja.com.au/public/issues/194_02_170111/baa10523_fm.html.

Peter D Baade · Danny R Youlden · Suzanne K Chambers

Objective: To update our previous analysis of trends for prostate-specific antigen (PSA) testing, prostate cancer incidence, radical prostatectomy and prostate cancer mortality to assess whether men in rural and regional areas of Australia now have more equitable access to prostate cancer services, and improved outcomes.Design, setting and participants: Descriptive study using population-based data for Australian men aged 50–79 years from 1982 to the 2008–09 financial year (depending on data availability for each outcome measure).Main outcome measures: Age-standardised rates per 100 000 men and 5-year survival rates.Results: Overall, rates of PSA screening and radical prostatectomy increased, accompanied by reductions in mortality and improvements in survival throughout Australia. Incidence rates were similar for men in urban and rural areas. However, in the last year of data collection, for men in rural areas compared with urban areas, rates of PSA screening (21 267/100 000 v 24 606/100 000; P < 0.01) and radical prostatectomy (182.2/100 000 v 239.2/100 000; P < 0.01) remained lower, mortality remained higher (56.9/100 000 v 45.8/100 000; P < 0.01), and survival outcomes continued to be poorer (5-year relative survival, 87.7% v 91.4%; P < 0.01).Conclusions: With some limitations, these ecological data demonstrate that the use of diagnostic and treatment services among men living in rural areas of Australia remains lower than among their urban counterparts, their survival and mortality outcomes are poorer, and these differentials are continuing. There is an urgent need to explore further the reasons for these differences and to implement changes so these inequalities can be reduced.

Peter D Baade PhD · Danny R Youlden BSc · Michael D Coory PhD · Robert A Gardiner MD · Suzanne K Chambers PhD

Androgen deprivation therapy (ADT) in men with prostate cancer increases the risk of osteoporotic fractures, type 2 diabetes and, possibly, cardiovascular events. There is considerable uncertainty about the risk–benefit ratio of ADT in non-palliative treatment; the benefits of ADT in treating non-metastatic prostate cancer need to be carefully weighed against the risks of ADT-induced adverse events. Baseline assessment of bone health at the initiation of ADT should include measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry and, in men with osteopaenia, a thoracolumbar spine x-ray. General measures to prevent bone loss, including regular physical activity, as well as ensuring calcium and vitamin D sufficiency, should be instituted routinely. All men with a previous minimal trauma fracture should receive pharmacological therapy unless contraindicated; for those who have not sustained a minimal trauma fracture, treatment is advised if the BMD T score is ≤ − 2.0, or if the 10-year risk of a major osteoporotic fracture exceeds 20%. Men with prostate cancer who are receiving ADT should be closely monitored for weight gain and diabetes; intensive lifestyle intervention is recommended to prevent ADT-induced weight gain and insulin resistance. Management of the metabolic sequelae of ADT includes optimal reduction of cardiovascular risk factors, with particular attention to weight, blood pressure, lipid profile, smoking cessation, and glycaemic control.

Mathis Grossmann MD, PhD, FRACP · Emma J Hamilton MB BS · Christopher Gilfillan MB BS, PhD, FRACP · Damien Bolton MB BS, FRACS · Daryl Lim Joon MB BS, FRANZCR · Jeffrey D Zajac MB BS, PhD, FRACP

Dose planning for prostate radiation therapy is performed using computed tomography (CT) scans that provide the electron density information needed for individual patients’ radiation dose calculations. For visualising the prostate and determining the target volume for radiation treatment, magnetic resonance imaging (MRI) gives vastly superior soft-tissue contrast. However, currently, MRI scans cannot be used for dose planning, as they do not provide the electron density information. We aimed to develop an alternative and efficient MRI-only image-based workflow, enabling both organ delineation and dose planning to be performed using MRI, with “pseudo-CT scans” generated from MRI scans supplying the information for dose planning. The feasibility of implementing MRI-based prostate radiation therapy planning is being investigated through collaboration between the clinical and medical physics group at the Calvary Mater Newcastle Hospital/University of Newcastle and the biomedical imaging processing group at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) Australian e-Health Research Centre. Results comparing Hounsfield units calculated from CT scans and from MRI-based pseudo-CT scans for 39 patients showed very similar average values for the prostate, bladder, bones and rectum, confirming that pseudo-CT scans can replace CT scans for accurate radiation dose calculations. MRI-based radiotherapy planning can also be used for tumours in other locations, such as head and neck, and breast cancers.

Peter B Greer PhD · Jason A Dowling PhD · Jonathon A Lambert BSc(Hons) · Jurgen Fripp PhD · Joel Parker BAppSc(MedRadScRadTherap) · James W Denham MD, FRCR, FRANZCR · Chris Wratten MB BS, FRANZCR · Anne Capp FRANZCR, FRCR, MMed(ClinEpi) · Olivier Salvado PhD

Objective: To examine the costs and cost-effectiveness of full implementation of biennial bowel cancer screening for Australian residents aged 50–74 years.Design and setting: Identification of existing economic models from 1993 to 2010 through searches of PubMed and economic analysis databases, and by seeking expert advice; and additional modelling to determine the costs and cost-effectiveness of full implementation of biennial faecal occult blood test screening for the five million adults in Australia aged 50–74 years.Main outcome measures: Estimated number of deaths from bowel cancer prevented, costs, and cost-effectiveness (cost per life-year gained [LYG]) of biennial bowel cancer screening.Results: We identified six relevant economic analyses, all of which found colorectal cancer (CRC) screening to be very cost-effective, with costs per LYG under $55 000 per year in 2010 Australian dollars. Based on our additional modelling, we conservatively estimate that full implementation of biennial screening for people aged 50–74 years would have gross costs of $150 million, reduce CRC mortality by 15%–25%, prevent 300–500 deaths from bowel cancer, and save 3600–6000 life-years annually, for an undiscounted cost per LYG of $25 000–$41 667, compared with no screening, and not taking cost savings as a result of treatment into consideration. The additional expenditure required, after accounting for reductions in CRC incidence, savings in CRC treatment costs, and existing ad-hoc colonoscopy use, is likely to be less than $50 million annually.Conclusions: Full implementation of biennial faecal occult blood test screening in Australia can reduce bowel cancer mortality, and is an efficient use of health resources that would require modest additional government investment.

Michael P Pignone MD, MPH · Kathy L Flitcroft BBSc, MA(Govt), GradCertHlthPolicy · Kirsten Howard MPH, MHlthEc, PhD · Lyndal J Trevena MB BS, MPhilPH, PhD · Glenn P Salkeld MPH, PhD · D James B St John MD, FRACP, AGAF

Palliative care is becoming fundamental in the starting line-up of care choices For Australian patients with advanced, incurable illness, particularly cancer, the option of referral to specialist palliative care services can seem to be a random and discretionary default option that is sometimes called on when all possibilities for life-extending treatment have been exhausted or cannot easily be accessed. Palliative care services (distinct from palliative chemotherapy) provide a broad range of inputs to patients and their carers and loved ones, including specialised medical and nursing management and advice on symptom control; psychological, emotional and spiritual support; practical nursing care; advice and assistance with goal setting and end-of-life care; and bereavement counselling and support. Despite offering these and other unique strategies in the field of cancer management, these specialist palliative care services sometimes stay on the substitute’s bench until called on late, when all else has failed. In Australia, despite having had principles of goal setting and broad palliative care education as part of the medical curriculum for over 20 years,1-3 and despite evidence of the benefits of referral to specialist palliative care services,4 only 42% of patients who die of advanced cancer and other terminal illnesses in the country’s busiest acute hospital are referred to a specialist palliative care service.5 Patients with haematological malignancies are referred less frequently than patients with solid tumours.6 Although oncologists in Australia report that they favour early referral for specialist palliative care, with a concurrent rather than sequential model of care,7 patients are usually referred late. In one large, integrated Australian palliative care service, patients had a median length of survival after referral of 54 days, representing the final 17% of their illness duration.8 Perceived barriers to improving palliative care referral and provision include inadequate communication about goal setting and resuscitation orders; inadequate symptom control; and lack of resources, including inadequate bereavement counselling of caregivers.7 A Queensland senator recently called Australian palliative care services “an under-resourced shambles”.9 In Australia and elsewhere, there have been increasing efforts to more accurately define the benefits or otherwise of early referral to palliative care services for patients with an incurable and progressive illness. However, research has been difficult, and randomised controlled trials have not been of high impact. Now, the results of two recent prospective, randomised studies from the United States10,11 will help to broaden Australian clinicians’ and the public’s understanding of the role of specialist palliative care services in the care of patients with advanced, incurable cancer and the advantages of early referral. Although the evidence from these studies has limited application in Australia because of differences in the US and Australian health care systems, the models of care being tested are similar to current Australian models, and the results have the potential to significantly shape practice and policy in this increasingly important part of health care.9 A non-blinded randomised controlled trial reported by Temel and colleagues10 provides a watershed moment in oncology and palliative care. One hundred and fifty-one ambulatory patients referred to an outpatient thoracic oncology clinic for newly diagnosed non-small cell metastatic lung cancer were randomly allocated to standard oncology care with or without referral to a palliative care team. The primary outcome was change in health-related quality of life at 12 weeks. Patients in the early palliative care group had better quality of life and fewer depressive symptoms compared with those receiving only standard care (Box). The various goals of new interventions in cancer treatment include improving survival; reducing treatment toxicity; improving quality-of-life scores (eg, mood); and reducing the financial costs of treatment. This study achieved all these goals with just the modest intervention of an average of four visits from the specialist palliative care team in the first 12 weeks. Importantly, the median survival time of 8.9 months was at least as good as would be predicted and expected for the control group. The improvement in overall survival of 2.7 months (30%) for the intervention group who were referred for early palliative care was equal to or greater than that achieved for comparable patient groups with chemotherapy versus best supportive care12 or the addition of the new and very expensive targeted agents cetuximab or bevacizumab to chemotherapy.13,14 It was achieved despite significantly fewer patients receiving aggressive end-of-life care. The size of the survival benefit may have been reduced because 14% of the control group also received early referral to a specialist palliative care service for symptom control and had 1–2 palliative care visits during the 12 weeks. A survival advantage from early palliative care referral has been suggested previously,15 but will need to be replicated by studies in other care settings and in patients with other types of cancer. Possible weaknesses of this study are the lack of blinding and lack of patient comorbidity data. Extra time spent with health care professionals, rather than any specific palliative care intervention, may have contributed to the improvements seen. But if this were so, this effect would also have been expected in studies showing benefits of chemotherapy plus best supportive care versus best supportive care alone, whereas no difference was shown in survival advantage between these groups.12 Also, even though the patient groups were balanced for types of chemotherapy and other treatments at enrolment and for the number of courses of chemotherapy during the study, more detailed data on specific chemotherapy regimens are lacking. Wright and colleagues11 followed 333 patients with advanced cancer from their enrolment until their death. Those referred to specialist palliative care services had better outcomes when treated outside an acute hospital (Box). Assessment of their carers at enrolment and after the death of the patient showed that those who were assisted in providing care at home until the patient’s death had significantly less risk of developing post-traumatic stress disorder or prolonged grief disorder. In the future, as we seek to confirm and understand more about how these improvements were achieved in patients receiving specialist palliative care, early referral for palliative care should become part of all arms of any randomised trial of advanced cancer treatment, particularly when a new treatment is being compared with best supportive care or current best treatment. The results of the two studies discussed here provide the best evidence yet for the multiple benefits of early referral to palliative care services in the care of patients with advanced, incurable cancer. They show that early referral can improve all measurable outcomes for patients by as much as, or more than, new and expensive treatments. Further, they show that early referral can help patients and carers better understand and choose between their treatment options near the end of life, reducing futile use of finite medical resources, debilitating treatments such as continuing cycles of chemotherapy in very advanced stages of illness, and acute in-hospital interventions at the end of life. The incidence of subsequent emotionally and financially debilitating psychological and psychiatric sequelae in the carers of these patients can be reduced. Because of new high-quality evidence, palliative care is rapidly moving from being an ancillary and sometimes discretionary medical treatment option to being fundamental in the starting line-up of care choices for patients with advanced cancer. If early referral for specialist palliative care were an expensive new drug, it would quite appropriately be marketed as a major advance in improving the care of patients with incurable cancer. Two recent US studies showing benefits of early specialist palliative care in patients with advanced cancer: overview Temel et al10 Research question: Does early referral of ambulatory patients with newly diagnosed metastatic non-small cell lung cancer to a specialist palliative care service affect patient-reported outcomes, use of health services and quality of end-of-life care? Design Non-blinded randomised controlled trial; 151 lung cancer patients referred to an outpatient clinic Standard oncology care versus standard care with referral to a palliative care team (seen within 3 weeks, and at least monthly until death) Groups well balanced for all known prognostic factors, initial cancer therapy, and baseline quality of life and mood Quality of life and mood assessed at baseline and 12 weeks Data on end-of-life care derived from medical records Findings Patients assigned to early palliative care received an average of four palliative care visits in 12 weeks (range, 0–8 visits) Patients in the intervention group had better quality of life than patients assigned to standard care Proportion of patients with clinical depression decreased in the intervention group from 22% to 16% and increased in the control group from 25% to 38% (P = 0.01) Fewer patients with early palliative care compared with standard care received aggressive end-of-life care (33% v 54% of those who had died by time of analysis; P = 0.05). Median survival was significantly longer among patients receiving early palliative care (11.6 v 8.9 months; P = 0.02) Wright et al11 Research question: Is the place of death for patients with cancer associated with patients’ quality of life at the end of life and psychiatric disorders in bereaved caregivers? Design Prospective, longitudinal multisite study; 333 patients with advanced cancer and their caregivers Patients followed from enrolment to death (median, 4.5 months) Quality of life at end of life assessed by caregiver report within 2 weeks of death Caregivers’ mental health assessed at baseline, and 6 months after patient’s death Findings Patients who died in an intensive care unit or hospital experienced more physical and emotional distress and worse quality of life at the end of life compared with patients who died at home with palliative care Death in an intensive care unit was associated with a greater risk of post-traumatic stress disorder in carers compared with death at home with palliative care (21.1% v 4.4%; P = 0.02) Death in hospital was associated with heightened risk for prolonged grief disorder in carers compared with death at home with palliative care (21.6% v 5.2%; P = 0.02)

Ian E Haines MB BS, FRACP, FAChPM

Objective: To report the latest conditional survival estimates for patients with cancer in Queensland, Australia.Design, setting and participants: Descriptive study of state-wide population-based data from the Queensland Cancer Registry on patients aged 15–89 years who were diagnosed with invasive cancer between 1982 and 2007.Main outcome measure: Conditional 5-year relative survival for the 13 most common types of invasive cancer, and all cancers combined.Results: The prognosis for patients with cancer generally improves with each additional year that they survive. A significant excess in mortality compared with the general population ceases to occur within 10 years after diagnosis for survivors of stomach, colorectal, cervical and thyroid cancer and melanoma, with these groups having a conditional 5-year relative survival of at least 95% after 10 years. For the remaining cancers we studied (pancreatic, lung, breast, prostate, kidney, and bladder cancer, non-Hodgkin lymphoma, and leukaemia), conditional 5-year relative survival estimates (at 10 years after diagnosis) ranged from 82% to 94%, suggesting that patients in these cohorts continue to have poorer survival compared with the age-matched general population.Conclusions: Estimates of conditional survival have the potential to provide useful information for cancer clinicians, patients and their carers as they are confronted by personal and surveillance-related decisions. This knowledge may be effective in building realistic hope and helping people manage uncertainty about the future. We suggest that measures of conditional survival be incorporated into routine statistical reporting in Australia.

Peter D Baade PhD · Danny R Youlden BSc · Suzanne K Chambers PhD

EpiphanyRex and John, both Australian neurosurgeons, were attending a conference in Oxford. That high summer day on the deck of the Head of the River relaxed by his ploughman’s lunch and ale Rex looked into the cloudless sky saw several far-off small black dots: maybe Canada geese, if not maybe, he smiled, a replay of the Battle of Britain. Hard to be certain ... But the dots stood still. Rex set down his glass stunned by rapid-fire thoughts of probabilities. “I think”, he said quietly to John “I have secondaries in my brain”. Ten years ago Rex had a melanoma on his back. There were questions then. “One never knows”, his surgeon said. “Are you sure they’re not floaters?” Rex closed each eye in turn. “Positive.” he said. “Migraine aura?” “Never before.” Rex knew the drill. For a decade he had savoured each day freed it from bureaucracy and strife. Fancy him, a wise man from the east receiving this epiphany in Oxford — Oxford, home of Tolkien and other master weavers of fantasy — this clear, prosaic sentence! How ironic that its execution would be inside his head! “I think that we should finish lunch”, Rex said slowly. John touched his arm. Both turned again to their cheese, meat and bread, emptied their glasses and left with the calm they assumed as they emerged from theatre weary with effort, seeking relatives in the waiting room desperate for news of a miracle to confess that it was not within their powers to remove all their loved one’s tumour though they’d tried for hours.

Stephen R Leeder MD, PhD, FRACP

CorrectionOmitted acknowledgement: In “Twenty-five years of treatment for childhood acute lymphoblastic leukaemia in Western Australia: how do we compare?” in the 15 November 2010 issue of the Journal (Med J Aust 2010; 193: 585-589), it was not acknowledged that Professor M K Bulsara and Professor K Hird of the School of Medicine, University of Notre Dame, Fremantle, WA contributed to the design and analysis of the study. The html and pdf versions of this article were corrected on 12 Jan 2011.

Hannah Forward · Guicheng C Zheng · Catherine H Cole

Bob Barter, who contributed much to the establishment of gynaecological oncology and neonatal pathology services in Western Australia, died recently in Perth at the age of 85. Bob was born in Perth on 27 January 1925. He was educated at Scotch College, Perth, where he was dux of the school in his final year. As there was no medical school in WA at the time, he studied medicine at the University of Adelaide, completing his undergraduate degree in 1949 and a doctorate (on the pathology of lung disease in premature babies) in 1952. He was then awarded a Nuffield Fellowship to study at King’s College in London. Bob returned to Australia in 1954 and worked briefly as a Senior Lecturer at the University of Adelaide before taking an Assistant Pathologist position at the Royal Women’s Hospital in Melbourne in 1955. When a position as Senior Lecturer at the new Faculty of Medicine at the University of Western Australia became available in 1960, he returned with his family to Perth. He was subsequently appointed Associate Professor and Director of the newly established Pathology Department at King Edward Memorial Hospital for Women (KEMH). Apart from a sabbatical year spent as Visiting Professor at Ohio State University in Columbus, Ohio, in 1967, Bob remained at KEMH. During his time at KEMH, community cytological screening for cervical cancer was initiated in Australia. In its early days, it was viewed with considerable scepticism; indeed, the program in WA almost foundered due to lack of standardisation of laboratory cytological examination and reporting, but Bob took on the training and accreditation of scientific staff to a high standard and the crisis was averted. From 1970 to 1972, he was a consultant to the World Health Organization program that was establishing cytology services in Indonesia. From 1976, Bob played a crucial role in the newly established gynaecological oncology service at KEMH. He conducted weekly Tumour Board multidisciplinary meetings until his retirement, making a major contribution to the management of women with gynaecological cancer. He taught medical undergraduate and postgraduate students throughout his career, and had a long association with the Cancer Council Western Australia, serving as its president from 1974 to 1978. In 1990, he was made a Member of the Order of Australia in recognition of his services to medicine. After retirement in 1985, Bob turned his restless intellect and energy to other pursuits, including farming, travel, foreign languages and reading. The last 10 to 15 years of his life were dogged by failing health, which he faced with great fortitude. A series of strokes left him with increasingly severe dysphasia, and eventually resulted in his being unable to read. Despite his progressive incapacity, Bob remained interested in people and the world, and did not lose his sense of humour. This was in large measure made possible by the unfailing love and support of Lyle, his wife of 57 years. Bob died peacefully in hospital on 12 October 2010. He is survived by his wife Lyle, daughter Ann and son Graham, and predeceased by his older son Michael.

Toby T Nichols · Ian Hammond

This article reflects on 30 years of conducting the Melbourne Colorectal Cancer Study, a comprehensive, population-based investigation of colorectal cancer (CRC). The study had an incidence arm, a case–control arm and a survival arm, and contributed considerable knowledge about CRC risk, aetiology, prevention and screening. The incidence arm: confirmed high rates of CRC in Australia and the prevalent view that rates rise in first-generation immigrants from countries with low rates of CRC; and enabled the first report of high rates of colon cancer among Australian Jewish people and the first report of high rectal cancer rates anywhere. The case–control arm elicited: the contribution of family history, antecedent colorectal polypectomy and multiple antecedent stressful life events to CRC risk; the risk of rectal cancer in habitual beer drinkers; the first dietary risk score (emphasising the importance of a diet pursued over adult life that is high in foods of plant origin and fish, and low in fat and red meat); and the highly protective effect of regular aspirin use (stimulating much research globally, with the possibility of aspirin becoming an important preventive agent). The survival arm: found an adjusted CRC-specific 5-year survival rate of 42% among patients with CRC and 85% among matched control subjects; confirmed cancer stage as the most important single determinant of survival; and found that the survival rate among people with the earliest stage of CRC was only marginally lower than that of matched community control subjects, underlining the importance of early detection.

Gabriel A Kune MD, FRACS, FRCS

Objective: To describe an in-depth analysis of the content and quality of stories about new cancer interventions in Australian media.Design and setting: Search of the Media Doctor Australia media-monitoring website for stories about newly reported cancer interventions, including drugs, diagnostic tests, surgery and complementary therapies, that had been collected from June 2004 to June 2009 and rated for quality using a validated rating instrument. A mixed-methods approach was used to analyse data and story content. Data from the website on stories about other new health interventions and procedures were compared.Main outcome measures: Differences in quality scores between cancer-related news stories (“cancer stories”) and other stories, and between types of media outlet; differences in how cancer was reported in terms of cancer type, morbidity, mortality, and in the use of hyperbole and emotive language.Results: 272 unique cancer stories were critically reviewed by Media Doctor Australia. Cancer stories had significantly higher scores for quality than other stories (F = 7.1; df = 1; P = 0.008). Most cancer stories concerned disease affecting the breast or prostate gland, with breast cancer appearing to be over-represented as a topic relative to its incidence. Pairwise comparisons showed statistically significant superiority for broadsheet newspaper stories over online stories (F = 12.7; df = 1; P < 0.001) and television stories (F = 10.7; df = 1; P = 0.001). Descriptions of morbidity and mortality were variable and often confusing in terms of numbers, time periods and locations. Literary devices including hyperbole and emotive language were used extensively, mostly by the researchers.Conclusions: While reporting of cancer in the general media is of low quality, many of the poorer aspects of content are directly attributable to the researchers. Researchers and journals need to do more to ensure that a higher standard of information about cancer is presented to the media.

Amanda J Wilson PhD · Billie Bonevski PhD · Alison L Jones FRCP · David A Henry FRCPE

Objective: To document presenting symptoms, investigations and management for Australian patients with oesophageal adenocarcinoma (OAC), gastro-oesophageal junction adenocarcinoma (GOJAC) and oesophageal squamous cell carcinoma (OSCC).Design, setting and participants: Cross-sectional study of a population-based sample of 1100 Australian patients aged 18–79 years with histologically confirmed oesophageal cancer diagnosed in 2002–2005, using data from cancer registries and treatment centres, supplemented with clinical information collected through medical record review in 2006–2007 and mortality information collected in 2008.Main outcome measures: Prevalence of primary symptoms, and staging investigations and treatment modalities used.Results: The primary presenting symptom was dysphagia, which was self-reported by 41%, 39% and 48% of patients with OAC, GOJAC and OSCC, respectively. Less common symptoms were reflux, chest pain, bleeding and weight loss. All patients underwent endoscopy, most had a staging computed tomography scan (OAC 93%, GOJAC 95% and OSCC 93%), and about half had positron emission tomography scans (OAC 51%, GOJAC 44% and OSCC 42%). Pretreatment tumour stage was reported in 25% of records, and could be derived from results of investigations in a further 23%, but the remaining half lacked sufficient information to ascribe a pretreatment stage. Curative treatments were attempted for 60% of OAC, 88% of GOJAC and 65% of OSCC patients. Surgery was performed on 52% of OAC, 83% of GOJAC and 41% of OSCC patients. About two-thirds of surgical patients received additional therapies.Conclusions: With anticipated increases in oesophageal cancer incidence, the resources required to diagnose and manage patients with oesphageal cancer are also likely to rise. Our data provide a baseline from which to plan for the future care of patients with cancers of the oesophagus.

Bernard M Smithers MB BS, FRACS, FRCS · Paul P Fahey BSc, MMedStat · Tracie Corish RN · David C Gotley MD, FRACS · Gregory L Falk FRACS, FACS · Garett S Smith MS, FRACS · George K Kiroff MB BS, MS, FRACS · Andrew D Clouston MB BS, PhD, FRCPA · David I Watson MD, FRACS · David C Whiteman MB BS,PhD, FAFPHM

Objectives: To compare survival among the subgroup of children with acute lymphoblastic leukaemia (ALL) who were treated at Princess Margaret Hospital for Children (PMH) in Perth, Western Australia, over 25 years under 15 consecutive protocols of the Children’s Cancer Group (CCG) with survival for the entire cohort of children in multiple centres treated under CCG protocols in that period; and to highlight the benefits of membership of a large cooperative research group conducting multicentre randomised controlled trials.Design, participants and setting: Retrospective review of the outcomes of all 311 children with newly diagnosed ALL treated at PMH between 1983 and 2008.Main outcome measures: 4-year event-free survival; and 10-year overall survival.Results: Four-year event-free survival for the entire PMH cohort increased from 66% (SE, 6%) for 1983–1987 to 88% (SE, 6%) for 2002–2005, while overall survival over the same period improved from 78% (SE, 5%) to 94% (SE, 4%). Comparisons of outcomes of children treated at PMH with those of the entire CCG cohort, protocol by protocol, revealed similar outcomes.Conclusion: Outcomes of children treated at PMH over the 25-year period are equivalent to those of the larger CCG cohort.

Hannah Forward MB BS(Hons) · Guicheng C Zheng PhD · Catherine H Cole MB BS, FRACP, FRCPA