Cancer

Objective: To examine cancer incidence and mortality in Indigenous Queenslanders.Design, setting and patients: Assessment of indirectly standardised incidence and mortality ratios for Indigenous Australians in Queensland diagnosed with cancer from 1997 to 2006, compared with the total Queensland population.Main outcome measures: Standardised incidence and mortality ratios.Results: Compared with the total Queensland population, Indigenous Queenslanders had a lower overall incidence of cancer (standardised incidence ratio, 0.79; 95% CI, 0.75–0.82), but a higher incidence of some of the more fatal cancer types. Overall cancer mortality was higher (standardised mortality ratio, 1.36; 95% CI, 1.28–1.45) and similar to rates for Indigenous people in other Australian states.Conclusion: Cancer rates for Indigenous Queenslanders, a mostly urbanised population, are similar to rates for Indigenous Australians mostly living in remote areas.

Suzanne P Moore BHSc(Nursing), MPH, PhD · Peter K O’Rourke BSc(Hons) BA(Hons), PhD · Kylie-Ann Mallitt BSc(Hons) · Gail Garvey BEd, MEd · Adèle C Green MB BS, MSc, PhD · Michael D Coory MB BS, PhD, FAFPHM · Patricia C Valery MD, MPH, PhD

To the Editor: An editorial by Stewart alludes to the problem of silent multiple comparisons when interpreting P values from cancer cluster investigations.1 Visible multiplicities such as occur with pre-specified subgroup analyses or sequential monitoring of trials are difficult enough, but at least in these circumstances we know how many multiple comparisons are under consideration. More difficult are silent multiplicities such as occur with cluster investigations (and also with publication bias2 or reporting bias3) where we do not know how many multiple comparisons should be considered. The P value is intended to be an objective measure of the play of chance, and this is (arguably) the case when applied to a pre-specified primary hypothesis in a randomised trial. But this is not the case for cluster investigations, in which the number of multiple comparisons can never be known with any certainty. Statisticians analysing data from a cluster could obtain any P value they wanted by calibrating it against an arbitrary number of multiple comparisons. Where does this leave scientific reasoning in cluster investigations? All cases of cancer have causes; the key question in a cluster investigation is whether the cases have a common cause related to the neighbourhood or workplace from which the cluster was reported. Only rarely is an obvious common cause identified, and a decision to take some action (eg, evacuate the workplace) needs to be based on expert opinion. For the ABC cluster, no obvious common cause was identified. However, the expert panel was concerned that the women with breast cancer were relatively young and were long-term employees at the site, suggesting that there might be an unidentified common cause related to the site.4 This concern, based on expert opinion, is (arguably) enough evidence to evacuate the site. Investigation of cancer clusters is a difficult task. If a common cause cannot be identified, then there is no objective evidence on which to obtain agreement among experts about the importance of the cluster. Specifically, we need to be very clear that, for cluster investigations, a P value (even when adjusted for multiple comparisons) does not provide an objective measure of whether the cluster is due to chance. In the end, an expert group has to make a decision in the presence of uncertainty. When communicating the results to the public, the uncertainty should be acknowledged — as should the fact that experts sometimes disagree.

Michael D Coory

To the Editor: We read with interest the report by Sitas and colleagues about the Australian Broadcasting Corporation (ABC) breast cancer cluster investigation.1 After publication of the final report on the ABC cancer cluster,2 the Public Health Unit of Sydney South West Area Health Service undertook a similar investigation. In May 2007, our Public Health Unit was contacted by an occupational health representative after reports of five recent cases of breast cancer among women working in two departments at a Sydney hospital between 2002 and 2006. Four of these cases were confirmed, and all four women had offices in the same area of the hospital. Based on the assumption that women employed in these two departments between 2001 and 2006 (a total of 69 women) were the population “at risk”, we found that there was an excess of observed cases over expected cases (standardised incidence ratio [SIR], 15.1 [95% CI, 4.1–38.8]; P < 0.001). There were no known hazards affecting these women that would not be present elsewhere in the hospital, so an expert panel recommended a hospital-wide epidemiological investigation and environmental survey. The case definition was any woman diagnosed with invasive breast cancer while working at the hospital between 1 January 1998 and 31 August 2007. To ascertain cases, we wrote a letter to all current employees and issued a media release. A dedicated telephone hotline received 147 calls from 19 July to 31 August 2007. We confirmed 24 cases meeting the case definition. These women had a mean age of 51 years at diagnosis, had worked at the hospital for a median of 11 years, were not clustered by work location or type, and had similar risk factors for developing breast cancer to women in the New South Wales population as a whole. From employment records and NSW cancer statistics, we calculated that 23 cases of invasive breast cancer would be expected based on the age structure and size of the female workforce at the hospital over the study period. The observed number of cases was not significantly different from the expected number (SIR, 1.1 [95% CI, 0.7–1.6]; P = 0.44).3 In the environmental survey, no unusual hazards were identified. Breast cancer is the most common invasive cancer diagnosed in Australian women.4 In most cases, potential “clusters” are probably a chance occurrence, even when the number of cases is statistically significantly higher than expected, with no plausible explanation identified.5 Our investigation found no excess of cases of breast cancer in women employed at the hospital over the study period. Guidelines6 are helpful in defining a consistent approach to cluster investigation, but such investigations are resource intensive. Careful initial analysis of information is important to determine whether further investigation of a reported cluster is warranted. In our study, we concluded that a broader investigation was justified.

Catherine Francis · Trish F Mannes · Leena Gupta · Stephen J Conaty

To the Editor: Flitcroft and colleagues’ discussion of the National Bowel Cancer Screening Program provides a useful reminder of how political, institutional and financial issues can affect evidence-based policy.1 Bowel cancer is second to prostate cancer as the biggest cause of cancer death in Australian men, and men are more likely than women to be diagnosed with bowel cancer. There are no indications, however, that the screening program has sought to engage men as a target group. Men and women think about and act on their health in different ways and respond differently to messages, sources of information and modes of information delivery.2 Men are less likely than women to undergo preventive screening and are more likely to seek treatment at a later stage in a disease. A report for the Australian Government noted that, before receiving the Bowel Cancer Screening Pilot Program material, men were less likely to have been aware of preventive or pre-emptive behaviours “unless their GP had actually raised the subject with them, or a close friend had suffered, bringing the issue to a more personal level”.3 Further evidence indicated that fewer than one-third of men participated in the screening from mid 2006 to mid 2007, despite men aged 55 and 65 years being more likely than women to return positive results; among men aged 55 years, only 28% chose to participate.4 Participation rates during the 2-year screening period ending August 2008 were estimated to be 39.2% for men and 46.7% for women.5 Despite the considerable evidence that the “doing of health” is a highly sex-dependent activity, a population-based, “one size fits all” approach appears to have been adopted. Adding further insult to injury, men were blamed for their lower participation rate and for failing to understand “that screening for cancer saves lives”.6 A disappointing response to a free breast cancer screening initiative, on the other hand, prompted an investigation into the relationship between the wording of the screening invitation letter and the level of screening attendance.7 With around one in 19 men predicted to develop bowel cancer before the age of 75 years, men’s under-representation in bowel cancer screening is a serious problem. There is a need for more attention to be given to men’s attitudes and beliefs about risk and prevention, with a view to developing specific approaches to increase men’s participation in screening.8 It should not be too much to expect that Australia’s first National Men’s Health Policy, and an updated National Women’s Health Policy, will result in sex being taken into account in the design and implementation of national health initiatives.

Margo H Saunders · Anita Peerson

To the Editor: Flitcroft and colleagues’ historical report of bowel cancer screening in Australia is helpful to those new to this internationally accepted life-saving practice.1 One inaccuracy needs correcting. Lung cancer is the leading cause of cancer death in Australia — not prostate or breast cancer. Flitcroft et al appear to have quoted the Australian Institute of Health and Welfare data for new diagnoses, not cancer deaths.2 This error reflects the general lack of community focus or interest in the more than 7000 Australians who die each year from smoking-related lung cancer.3 An update is also warranted. Since submission of their article, once-only flexible sigmoidoscopy screening has joined faecal occult blood test (FOBT) screening in having randomised controlled trial evidence. Results of a recent British study point to the necessity of looking for this occult disease with flexible colorectal endoscopy.4 The study showed a massive 43% reduction in colorectal cancer mortality and a 50% reduction in incidence of invasive rectal cancer, owing to early flexible sigmoidoscopic diagnosis of colonic polyposis followed by polypectomy performed at subsequent colonoscopy. These techniques save thousands of lives worldwide each year. Flitcroft et al state that “A staged roll-out is a sensible approach”, but many of us who perform colonoscopic polypectomies on a weekly basis strongly disagree. Which is better — to be on a waiting list for a colonoscopy with a positive FOBT result, or to be ignorant of the possibility of a growing cancer in the colon? It is time to give people the opportunity of FOBT with or without further investigations. Flitcroft et al rightly point out that the National Health and Medical Research Council recommended that we should have at least biennial FOBT screening for individuals over 50 years of age.5 Australians have been very tardy in terms of adopting this recommendation. We don’t need an “age-specific cost-effectiveness analysis”. The argument should be about introducing flexible sigmoidoscopy. Like Semmelweis and hand washing back in 1847, history will judge our current generation harshly for ignoring the original life-saving FOBT research that was published in 19936 and allowing thousands of Australians to die unnecessarily from bowel cancer since then. It is time for us to take our heads out of the sand and introduce a proper national bowel cancer screening program. Thank you to Flitcroft and colleagues for helping us take another step in this direction.

Guy R Hingston

CorrectionMissing authors: In “Pathways to the diagnosis of epithelialovarian cancer in Australia” in the 20 September 2010 issue of the Journal (Med J Aust 2010; 193: 326-330), two study groups were omitted from the list of authors. The Australian Cancer Study (Ovarian Cancer) and the Australian Ovarian Cancer Study Group should have been listed as the final two authors, as shown here.

Susan J Jordan MB BS, FRACGP, PhD · Jane E Francis MA, MPH · Anne E Nelson PhD · Helen M Zorbas MB BS, FASBP · Karen A Luxford BSc(Hons), PhD · Penelope M Webb MA, DPhil

To the Editor: I agree with Emery and colleagues1 that family history can add much to downstream clinical interventions that provide tangible benefits to the presenting patient and his or her kin. The pedigree chart has some advantages over simple narrative recording of the same details, including the ability to instantly visualise relationships between individuals and the ease with which the chart can be updated and annotated.2 There is a familial aggregation (commonly an affected first-degree relative) in up to 25% of presenting cancer patients, while around 5% will harbour a highly penetrant genetic predisposition to cancer. In the cancer clinic, an acceptably detailed family cancer pedigree can typically be obtained in even less time than the 30 minutes suggested by Emery et al.1 Steps in drawing pedigrees have been outlined elsewhere2,3 and typically involve collecting information such as simple demographics, naming and symbolising different cancer types, and recording age of onset and age of death (if relevant) for the different individuals, starting with the presenting patient. The time required to construct a three-generation pedigree would typically be around 10 minutes, making it an attractive addition to routine history taking. If a cancer pattern emerges, the pedigree should be extended as far as possible. Of course, diagnosis verification (through death registries, etc) would be required before surveillance, prophylaxis and therapy decisions are addressed in the familial cancer setting. A convenient refresher for doctors who do not routinely draw pedigrees might be to first construct their own family tree, with reference to the symbols and relationship illustrators commonly used.2,3 It is likely that pedigrees in most clinics will be drawn by hand, at least initially, although there are software programs for pedigree creation available (eg, Family Tree Builder; <http://www.myheritage.com/family-tree-builder>). Over the years, I have informally asked my specialist oncology trainees to routinely construct family pedigrees. I do not recall, among these highly clinically skilled doctors, one that was able to correctly draw a family pedigree until we had worked on it together. Given the benefits of family pedigree analysis across many disease categories, a little practice in pedigree drawing may be a useful exercise for many of us. Even without the requisite confirmation of disease status of the individuals represented, a simple pedigree chart, combined with quick reference to information on the potential clinical significance of any patterns it shows (eg, by consulting National Health and Medical Research Council guidelines),4 can help prioritise referrals to busy familial cancer clinics.

Michael J McKay

To the Editor: Langlands and colleagues show that family history is poorly taken in patients presenting to an acute medical unit at a major tertiary hospital.1 However, their article and its companion editorials2,3 do not adequately stress the settings in which family history taking may be both easily achievable and most cost-effective. The nihilism that Thomas and Thompson2 convey about recording family history in the acute setting is of more concern, given that a tertiary hospital may offer the best opportunity to initiate the process of case detection for a number of heritable and lethal diseases, such as autosomal dominant familial hypercholesterolaemia (FH), the most common monogenic cause of premature coronary artery disease (CAD). We previously demonstrated that a family history of cardiovascular disease was almost never recorded by coronary care unit medical staff at Royal Perth Hospital.4 For 509 patients aged < 60 years presenting with symptomatic CAD to the coronary care unit, we found that 70% had insufficient clinical data documented in the medical records to enable a diagnosis of FH. In a follow-up study of 103 patients with premature CAD admitted to the coronary care unit, a nurse practitioner was able to record a positive family history of premature cardiovascular disease in a primary relative for 43% of patients, of whom 95% had phenotypic FH based on a recognised clinical diagnostic tool (the Dutch Lipid Clinic Network score).5 Patients detected in this way in Western Australia are now referred to a statewide FH program run by staff from a lipid clinic.5 In this program, where detailed pedigree drawing and family tracing is performed by trained nurses, we have found a causative mutation for FH in up to 85% of patients with a clinical phenotype strongly suggestive of FH. Additionally, we find that for every index case so detected, we can additionally diagnose at least three new cases of FH in the patient’s relatives, many of whom are young. This method of case detection and subsequent treatment with cholesterol-lowering therapies is highly cost-effective and, more importantly, enables therapy to be targeted at younger patients, thereby maximising the potential for preventing CAD. Our experience illustrates that for a lethal condition such as FH, an accurate family history recorded by a nurse can spark a cascade of action that leads to a definitive diagnosis of FH in the index patient and the subsequent detection of otherwise undiagnosed FH in the community, with significant associated cost savings.6 Hence, we propose that nursing staff can efficiently bridge this gap in medical care while we are getting our house in order by training medical staff to effectively take a family history.

Timothy R Bates · Elissa B Poulter · Frank M van Bockxmeer · Gerald F Watts

To the Editor: I read the article by Langlands and colleagues1 with some dismay, and a sinking heart. Their report is further evidence of the dangers of moving away from the basic skills of comprehensive history taking and performing a detailed physical examination. Interestingly, in the United States, the debate regarding performing a physical examination has come full circle, from virtually ignoring its importance to now telling us how vital it is and how to perform it.2 But it is the taking of a comprehensive history that, as one of my mentors told me, “is where the money is”, and a detailed family history is an integral part of this. Eliciting a detailed family history is arguably more important for paediatric patients, who have a longer potential life span and hence have more to gain from this information. In my paediatric practice, for example, I see numerous overweight children, some of whom have a strong family history of hypercholesterolaemia, vascular disease or type 2 diabetes mellitus, which places them at considerable risk of cardiovascular disease in their adult years. A detailed family history may also “unmask” the genetic contribution to a child’s history of deafness or learning disability. Time constraint is the main impediment to taking a comprehensive family history, but it is worth keeping in mind that it is time well spent and that, in the paediatric population, it may make a significant contribution to the long-term health of the child. With the impending advent of personalised genomic screening, there will be an even greater imperative to formalise the gathering of family history details.3,4

Simon E P Hauser

Objective: To describe the diagnostic pathways experienced by a large, representative group of Australian women with ovarian cancer, and to document the time between first presentation to a medical professional and clinical diagnosis.Design, setting and participants: 1463 women with epithelial ovarian cancer from an Australia-wide population-based study (2002–2005) completed a telephone interview in which they described the events that led to the diagnosis of their cancer.Main outcome measures: Number and type of doctors consulted, investigations performed, referral patterns and the time from first presentation to diagnosis.Results: Of the 1463 women, 145 had their cancer diagnosed incidentally and were excluded from analysis. Most of the remaining 1318 women (1222, 93%) presented first to their general practitioner. As a result of their first medical consultation, 75 women (6%) were given a diagnosis, and 484 (37%) were referred to a gynaecologist, gynaecological oncologist or oncologist for further assessment. Overall, 85% of women visited three or fewer doctors before their cancer was diagnosed; 66% of cancers were diagnosed within 1 month of the initial presentation, and 80% were diagnosed within 3 months. For 12% of women, the diagnostic process took longer than 6 months; this was more likely for women residing in remote Australia, those with lower incomes, and those presenting with abdominal pain or bowel symptoms, or with more than one symptom.Conclusions: Despite anecdotal suggestions to the contrary, most women with ovarian cancer in Australia are investigated and diagnosed promptly. The diagnostic process is more protracted for a minority of women, and the factors we found to be associated with diagnostic delay warrant further investigation.

Susan J Jordan MB BS, FRACGP, PhD · Jane E Francis MA, MPH · Anne E Nelson PhD · Helen M Zorbas MB BS, FASBP · Karen A Luxford BSc(Hons), PhD · Penelope M Webb MA, DPhil

To the Editor: I would like to correct some inaccuracies in an article by Jelinek and Gawler in the December 2008 issue of the Journal about a survivor of disseminated osteosarcoma.1 The article describes a 58-year-old man who was diagnosed in 1974, at the age of 24 years, with histologically confirmed high-grade osteosarcoma of the right femur. He underwent a full leg amputation in January 1975, but metastases recurred 11 months later, in December 1975. The authors of the article misreported a sequence of medically significant events, altering the patient’s actual history. (The correct chronology and early clinical history of the case have been published elsewhere.2,3) The errors and omissions in the article by Jelinek and Gawler, together with the correct sequence of events and relevant inclusions, are outlined in Box 1. In summary, the major errors in the article were as follows: Timeline errors. The authors stated that the patient first saw Dr Meares in September 1976, after chemotherapy had failed. In fact, the patient consulted Meares as a first-line treatment approach on 12 December 1975, and did not consider chemotherapeutic options until September 1976. The authors also stated that the patient had palliative radiotherapy in September 1976. In fact, the patient had only one course of palliative radiotherapy treatment, in February 1976. Vegan diet. The patient never followed a vegan diet. Date of photographs. The photographs in Figures B and C of the article by Jelinek and Gawler were taken on 7 July 1977 (Box 2), not at the time of first contact with Meares, as implied in the article. An appraisal of the patient’s symptoms, combined with an accurate clinical history, reveals a more plausible scientific hypothesis for his remission than the effects of diet and meditation. Although diet and meditation may be adjuncts to a patient’s wellbeing, it is unlikely in this case that they were curative, and certainly veganism was not a relevant factor. Immunotherapy with BCG vaccine treatments, the timing of symptoms and the patient’s eventual diagnosis of tuberculosis could be associated with his remission, as postulated by his radiation oncologist in 1978.6 There is extensive scientific literature about remission of cancer, including osteosarcoma, associated with febrile conditions.5,8-15 The patient’s sporadic visits to doctors meant that metastases were not diagnosed histologically and much of the information reported on his case is anecdotal. Clearly, in this and other cases, unbiased investigative scientific research needs to be undertaken before reporting anecdotes and extrapolations as if they were fact. Teasing apart the errors in Jelinek and Gawler’s story, now on the public record and almost medical myth, is an enormous task, but one that must be done, because correctly reporting the patient’s clinical timeline is crucial in any discussion about the causes of his remission and the flow-on effect to cancer patients and their treating doctors.16 1 Corrections to errors in the article by Jelinek and Gawler1 Errors and omissions in the article Facts, corrections and inclusions December 1975: widespread bony and pulmonary metastases were diagnosed. December 1975: an isolated metastasis in an inguinal node was diagnosed. The patient undertook the Gerson dietary regimen,4 immunotherapy with BCG vaccine,5 and the Meares intensive meditation program.6 September 1976: “[the patient] underwent three cycles of palliative chemotherapy with vincristine, adriamycin, cyclophosphamide and darcarbazine, as well as brief palliative radiation therapy”. September–October 1976: growth of tumours on the sternum increased, and metastases were detected in the left lung. Coughing and haemoptysis were present.6 Experimental chemotherapy (with adriamycin, vincristine and methotrexate)2 was ceased at 10 weeks after December 1976. No radiation therapy was given at this time. Palliative radiotherapy was administered in February 1976, not September 1976. September 1976: “He elected to discontinue these therapies as his condition deteriorated further.” “The patient then consulted prominent psychiatrist and hypnotherapist Dr Ainslie Meares ...”. December 1975: the patient first consulted Meares. In February 1976, he abandoned the Meares meditation program. The 10-month discrepancy between December 1975 and Jelinek and Gawler’s stated date of September 1976 (actual date, October 1976) alters the patient’s medical timeline, implying that it was only after other treatments had failed that meditation began and played a key role in his recovery. Dates of photographs shown in the article: “When Meares first saw the patient, he had visible bony tumours protruding from his ribs, sternum (Figure B) and iliac crest, and was coughing up blood containing small spicules of bone (Figure C).” The article by Jelinek and Gawler implies that the photographs in their Figures B and C were taken around the time when the patient first contacted Meares. The photograph in Figure B was actually taken on 7 July 1977, 19 months after his first contact with Meares. Tumours were not protruding from the sternum when Meares first saw the patient to begin meditation in December 1975, and there were no visible metastases. The coughing up of blood containing bone spicules (Figure C) began in mid 1977, not in the period between December 1975 and February 1976. Vegan diet: “[the patient] adhered faithfully to a vegan diet”. The patient never followed a vegan diet. Veganism involves exclusion of all animal products. The Gerson regimen4 includes dairy foods and calf liver juices. For the following 22 years, the patient’s diet included seafood, dairy products and eggs. First appearance of tuberculosis: “Presumably related to immunosuppression from chemotherapy, he developed pulmonary tuberculosis in June 1978, and was treated for this condition for 12 months.” In 1978, an oncologist diagnosed advanced tuberculosis (TB) dating back to early 1976. (Previous x-rays were examined, showing evidence that TB had been present and undiagnosed for at least 2 years. The patient had very advanced TB by June 1978.6) The suspected cause was BCG vaccine treatments administered in December 1975, possibly exacerbated by chemotherapy and associated immunosuppression in late 1976. 2 Original photographs of patient’s chest taken on 7 July 1977 I am in possession of these original photographs (left), which were dated 7 July 1977 (date enlarged in inset). A copy of page 227 from the original edition of You can conquer cancer7 also confirms the accurate date of the photographs as 7 July 1977 (date enlarged in inset)

Grace O Gawler

In reply: In conjunction with the patient’s memory, and teasing out details, where available, from medical records and investigations of over 30 years ago, we sought to piece together our follow-up story of a remarkable recovery from cancer as accurately as possible.1 We did not attempt to reproduce the original case report in the Journal,2 but rather were highlighting the long-term issues that can be associated with such recoveries. We thank Ms Gawler for attempting to clarify the original timelines. However, based on the medical records and published data, as well as checking further with the patient himself, it seems her letter does little more than muddy the waters in this case. Ms Gawler claims the patient abandoned the Meares meditation program in February 1976. This is factually incorrect and misleading. The patient continued to use Meares’ methods to meditate for 3 hours daily until he recovered, and has meditated at least 1 hour daily since then. The timelines quoted around the photographs in Figures B and C in our original article1 were based on information from Meares’ 1978 article.2 He was somewhat inaccurate, as is Ms Gawler, who claims the photos were taken in July 1977. This is incorrect. Figure B was photographed in July 1976 as chemotherapy was commenced. Figure C was photographed in 2008 and documents bony spicules coughed up during the first half of 1977, collected and retained by the patient. Regarding the use of BCG vaccine treatments, the patient reports that none of the three tuberculosis (TB) specialists whom he consulted gave credence to Ms Gawler’s suggestion that the onset of TB was related to the BCG vaccine. Ms Gawler further postulates that the remission could be linked to a febrile condition associated with TB. The patient did have severe night sweats (which may or may not have been accompanied by fever) over a period of 2–3 weeks in February and March 1976, at a time when he almost certainly had not yet contracted TB, and after which the metastases continued to grow rapidly. After this time, the patient never reported fevers that would make sense of this claim. Ms Gawler claims that the patient’s metastases were not diagnosed histologically and that much of the reported evidence is anecdotal. This is misleading and would surely surprise the involved surgeon, oncologist and other physicians, who used the best available medical evidence at the time and cooperated in the preparation of our original article. The case is documented with a thorough medical history, the patient’s surgeon and other specialists were consulted regularly, and accurate records were retained. Full details confirming the report are available in the patient’s biography.3 The metastases were thoroughly investigated and confirmed by the Peter MacCallum Cancer Centre in Melbourne and regularly tracked via x-ray. The original lesion seen on x-ray was diagnostic for osteosarcoma and the diagnosis was confirmed histologically by biopsy, and again after amputation. The case history is certainly complex and compelling. The message is clear: unexpected recovery from disseminated cancer remains a possibility, and is likely to be influenced by lifestyle factors.

George A Jelinek · Ruth H Gawler

Cancer care must incorporate the psychosocial and biological The clinical oncologists of all stripes have, for too long, overlooked or ignored the psychological factors that may, for all we know at present, play a surprisingly large role in individual susceptibility to neoplasia. They are certainly influential in affecting the course of treatment, the adaptation to the illness, and hence, in some ways, not all of which are yet understood, affect the outcome of treatment. Lewis Thomas in the foreword to the Handbook of Psychooncology, 19891 The publication of the Handbook of psychooncology,1 later to grow into the substantial textbook Psycho-oncology,2 heralded the beginning of the field of psychooncology. Psychological factors had long been linked with the cause or progress of much human illness, and yet were being increasingly ignored because of a lack of substantial evidence and a strengthening of the biological understanding of disease. The work represented by the publication of these volumes identified the beginning of both a clinical and research interest that continues strongly to this day. Cancer is the first field of medicine where psychosocial factors have been taken seriously. This was partly because of the potency of cytotoxic drugs and the severity of adverse effects. This led to a need to consider “quality of life”, and to balance this with gains in longevity of life. Quality of life is a subjective matter that requires consideration of complex psychosocial and relational matters and values. These cannot be measured by blood tests. In addition, cancer, more than any other disease, confronts us all with serious existential issues. It challenges the sense of control we might think we have over our lives, and raises the possibility of the purposelessness and futility of life, as well as raising questions about what is a good life and a good death. The field of psychooncology has contributed much over the years. We have seen serious attention given to communicating “bad news” to patients and to “truth telling”, maximising patients’ involvement in care decisions and maintaining dignity. Various behavioural and psychological interventions have been shown to be effective in relieving patients’ anxiety and depression. Attention has been given to the stress that carers and loved ones experience through the cancer journey, and how strained the support networks can be at times; at other times and for other people, the cancer journey can be a “growth” experience.3 The articles in this Medical Journal of Australia supplement showcase the quality of work currently being done in this area. They range from the use of a large epidemiological survey to tease out the connections between cancer and depression,4 to descriptions of systemic interventions of screening and psychosocial care.5 There is evidence for the effectiveness of psychosocial interventions in relieving distress and assisting in psychosocial adjustment for people in the experience of cancer, although much work remains to be done. Current levels of evidence have been well summarised in published National Health and Medical Research Council (NHMRC) guidelines.6 However, these interventions are not routinely offered by cancer services to patients and their families. So, despite the development of an evidence base over the past few decades, and the acknowledged good things happening in the clinical domain in the area of communication skills for health professionals,7 clinical practice lags behind evidence and standards of best practice. To correct this, we need champions in the field talking about the issue, consumers and carers participating in the research and sharing their experiences, and leading practice-policymakers and health providers with the moral courage to fully implement “evidence-based” and humane care beyond the trial phase. The importance of this is not diminishing as medical science takes us into new areas (such as genetic screening, which is producing a cohort of people who, while well, live with the anxiety of developing cancer at any time in their life), which throw up ever- new ethical and clinical challenges. beyondblue and Cancer Council Australia are committed to working together towards seeing the development of an integrated approach to cancer care incorporating the psychosocial and biological; and beyondblue will continue to encourage and support research that advances knowledge and improved practice in the area by investing in applied research and by partnering with Cancer Australia in the NHMRC’s Priority-driven Collaborative Cancer Research Scheme.

David M Clarke PhD, FRACGP, FRANZCP

Objectives: To examine the prevalence and predictors of depression and anxiety in palliative care patients with cancer in Western Australia and New South Wales.Design, setting and participants: A descriptive study of 266 consecutive patients at a range of inpatient and outpatient settings including home care, hospices, and private and tertiary care hospitals in WA and NSW from 1 March to 30 June 2002.Main outcome measures: Self-reported anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) at a cut-off score of ≥ 8 on each subscale (depression and anxiety) for possible cases, and of ≥ 11 for probable cases; a cut-off score of ≥ 19 was used for probable combined depression and anxiety.Results: Patients included 200 in WA and 66 in NSW. For the whole sample, 45.8% of patients were possibly depressed and 22.7% probably depressed; 36.9% were possibly anxious and 19.8% probably anxious. About 25% of patients had probable combined depression and anxiety. Logistic regression analyses indicated that past anxiety in the family predicted probable depression, while age, marital status and past depression predicted probable anxiety. Age and past depression predicted probable combined depression and anxiety.Conclusions: These findings underscore the need for routine screening for anxiety and depression in palliative care settings, including questions about past personal and family history of anxiety and depression, and the need for a range of interventions and support services.

Moira O’Connor BA(Hons), MSc, PhD · Kate White RN, MN, PhD · Linda J Kristjanson BN, MN, PhD · Kerry Cousins RN, BN · Lesley Wilkes PhD, RN, CM

Objective: To assess symptoms of depression and anxiety in patients with head and neck cancers (HNCs) before and after radiotherapy.Design, participants and setting: Prospective observational study of 102 outpatients with HNCs at a tertiary cancer centre in Melbourne between 1 May 2008 and 30 May 2009. Eligibility criteria were a first-time diagnosis of HNC, age over 17 years, and agreement to undergo cancer treatment involving radiotherapy with curative intent. Data were collected before commencement of radiotherapy and again 3 weeks after completing treatment.Main outcome measures: Symptoms of depression and anxiety as assessed by the Hospital Anxiety and Depression Scale (HADS); physical and psychosocial aspects of quality of life as assessed by the Functional Assessment of Cancer Therapy–Head and Neck (FACT-H&N).Results: Seventy-five participants completed pretreatment and posttreatment questionnaires. Mean depression scores increased significantly from before to after treatment, while anxiety scores decreased significantly over the same period. The prevalence of mild to severe depression was 15% before treatment and 31% after treatment. The prevalence of mild to severe symptoms of anxiety was 30% before treatment, reducing to 17% after treatment. Posttreatment depression was predicted by pretreatment depression and receiving chemotherapy. Posttreatment anxiety was predicted by pretreatment anxiety and male sex.Conclusions: These findings suggest that rates of depression in patients with HNCs increase after cancer treatment, with a third of patients experiencing clinically significant symptoms of depression after radiotherapy.

Kate A Neilson BBSc(Hons), DPsych(Clinical) · Annabel C Pollard RN, GradDipAppPsych. MPsych(Clinical) · Ann M Boonzaier BA(Hons), MA(Psychology), DPsych(Clinical) · June Corry MD, FRACP, FRANZCR · David J Castle MD, MRCPsych, FRANZCP · Karen R Mead BAHons(Psychology), MPsych(Clinical) · Marcelle C L Gray BA(Psychology), PGradDip(Psychology) · David I Smith BBSc(Hons), MPsych, PhD · Tom Trauer PhD, ABPsS, MAPsS · Jeremy W Couper MD, MMed(Psych), FRANZCP

Objectives: To assess the prevalence and predictors of depression and anxiety in women with ovarian cancer and their caregivers, to compare levels of depression and anxiety with community norms, and to explore the relationship between patients and their nominated caregivers.Design, setting and participants: Prospective cohort study of 798 women with invasive ovarian cancer recruited between 1 January 2002 and 30 June 2006 through the nationwide Australian Ovarian Cancer Study, and 373 of their caregivers.Main outcome measures: Depression and anxiety as assessed with the Hospital Anxiety and Depression Scale, and the role of demographic variables, disease and treatment variables, psychosocial variables, and use of mental health and support services as potential predictors.Results: Rates of anxiety and depression among patients were significantly lower than in previous reports, although clinical depression rates (5.9%) were significantly higher than community norms (3.0%; χ2 = 24.0; P < 0.001). Caregivers also reported higher levels of depression (χ2 = 21.1; P < 0.001) and anxiety (χ2 = 17.6; P < 0.001) compared with norms. There was no difference within patient–caregiver pairs for depression (P = 0.1), while caregivers reported significantly higher anxiety than patients (P < 0.01). In patients, higher symptom burden, lower optimism and current specialist mental health treatment all significantly predicted both depression and anxiety, while lower social support was a significant predictor of patient anxiety only. In caregivers, lower social support and lower optimism were significant predictors of depression and anxiety. Patients being treated for mental health was also a predictor of their caregiver’s depression.Conclusions: While depression is significantly more common in women with ovarian cancer than in the general population, it is caregivers of such patients who report much higher levels of both subclinical and clinical depression and anxiety.

, the Australian Ovarian Cancer Study Group and the Australian Ovarian Cancer Study Group Quality of Life Study Investigators

Objective: To investigate whether the observed elevated levels of psychological distress in cancer survivors relate specifically to aspects of cancer diagnosis, to treatment or to disability.Design, participants and setting: Self-reported questionnaire data on demographic, health and lifestyle factors and mental health from 89 574 Australian men and women aged 45 years or older, sampled from the Medicare database for the 45 and Up Study from 1 February 2006 to 30 April 2008. Logistic regression was used to examine the risk of high levels of psychological distress in relation to cancer diagnosis and disability, adjusting for age, sex, income and education.Main outcome measure: High psychological distress (Kessler Psychological Distress Scale score ≥22).Results: Overall, 7.5% of participants had high levels of psychological distress. Among cancer survivors, the median time since diagnosis was 7.3 years. Compared with people without cancer, the odds ratios (95% CIs) for psychological distress were: 1.17 (1.09–1.26) in people reporting having had any cancer apart from non-melanoma skin cancer; 1.34 (1.08–1.67) in those with cancer diagnosed in the previous year; 1.53 (1.33–1.76) for those reporting treatment for cancer in the previous month and 1.11 (1.03–1.19) for those with cancer but without recent treatment. Using individuals with neither cancer nor disability as the reference group, the adjusted odds ratio (95% CI) for psychological distress was 6.51 (5.95–7.12) in those reporting significant disability but no cancer, 1.14 (1.04–1.24) in those without disability but with cancer and 5.81(4.88–6.91) in those with both cancer and disability.Conclusion: The risk of psychological distress in individuals with cancer relates much more strongly to their level of disability than it does to the cancer diagnosis itself.

Emily Banks MBBS, PhD, FAFPHM · Julie E Byles PhD · Richard E Gibson BSc · Bryan Rodgers MSc, PhD · Isabel K Latz MSc · Ian A Robinson BSc · Anna B Williamson PhD · Louisa R Jorm BVSc, MSc, PhD

Objective: To evaluate the efficacy of an interactive self-help workbook in reducing distress, and improving quality of life (QOL) and coping for women recently diagnosed with breast cancer.Design: Randomised controlled trial comparing the use of the workbook and that of an information booklet.Participants and setting: 49 women with Stage 0 to II breast cancer diagnosed in the previous month and recruited from 1 February 2007 to 1 February 2008, in two urban Australian public hospitals.Main outcome measures: The primary outcome measures were depression, anxiety, and posttraumatic stress. Secondary outcomes included QOL, body image, and the coping styles helplessness/hopelessness, cognitive avoidance and anxious preoccupation.Results: After controlling for baseline levels, interactions at 3-month follow-up showed that participants in the workbook group had significantly lower levels of posttraumatic stress (F [1,89] = 7.01; P = 0.01), helplessness/hopelessness (F [1,89] = 4.75; P = 0.03), and cognitive avoidance (F [1,89] = 4.95; P = 0.03) than those in the control (information booklet) group. However, women in the workbook group had significantly poorer body image than those in the control group (F [1,89] = 6.43; P = 0.01). At 6 months, only the body image interaction remained significant (F [1,93] = 7.44; P = 0.01).Conclusion: These results suggest that a self-help workbook can be an effective, short-term intervention for improving posttraumatic stress, cognitive avoidance, and certain depressive symptoms in women recently diagnosed with breast cancer. However, issues related to body image need to be dealt with differently.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000934246.

Lisa J Beatty · Bogda Koczwara · Janet Rice · Tracey D Wade

Objective: The aim of this study was to characterise rates of late mortality and second cancers in an Australian cohort of childhood cancer survivors and compare these to rates observed in the New South Wales population.Design, setting and participants: Records for 896 childhood cancer survivors treated at the Sydney Children’s Hospital between 1972 and 1999 were linked to the National Death Index and NSW Central Cancer Registry to identify deaths and notifications of second cancers. Survivors were defined as those alive for at least 5 years after diagnosis and were followed until death or 31 December 2004, whichever occurred first.Main outcome measures: Standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs) were used as measures of relative risk. A Cox proportional hazard model was used to quantify the influence of demographic and disease-related characteristics on the risk of death and second cancers.Results: The SMR and SIR were 7.46 and 4.98 times higher, respectively, among cancer survivors relative to the NSW population. Relative mortality was highest in survivors of soft-tissue sarcoma (SMR, 18.95 [95% CI, 6.88–40.81]) and central nervous system (CNS) malignancies (SMR, 16.78 [95% CI, 7.62–31.64]). The leading causes of death included recurrence of the primary childhood cancer (55%) and second cancers (12%), as well as treatment-related complications (17%) The most frequently observed second cancers were bone and thyroid cancers, melanoma, and CNS malignancies, and second cancers were most common among survivors of leukaemia, soft-tissue sarcoma and Hodgkin’s lymphoma.Conclusions: Compared with the general population, survivors of childhood cancer in Australia are at increased risk of late mortality and second cancers. These findings highlight a continuing need to assess health issues faced by childhood cancer survivors and develop strategies to minimise the adverse outcomes associated with treatment for childhood cancer.

Carmen L Wilson BSc(Hons), PhD · Richard J Cohn MB BCh, FRACP · Karen A Johnston RN, MN · Lesley J Ashton MPH, PhD

Objective: To describe the outcomes and clinical experience of a 12-week pilot study of routine distress screening of newly admitted patients to an acute haematology and oncology ward.Design, patients and setting: Bedside measurement of psychological distress, and collection of demographic and clinical data for 115 newly admitted patients in an acute haematology and oncology ward of The Alfred hospital in Melbourne between 5 June and 25 August 2006.Main outcome measures: Psychosocial distress as measured by the Distress Thermometer and Problem Checklist, and 18-item Brief Symptom Inventory; rate of referral to psychology and social work services in the 12 weeks before and 12 weeks during the pilot study; ward staff feedback on the benefits and challenges associated with routine distress screening.Results: 51% of patients were identified as being significantly distressed, of whom 47% had not received psychosocial support before screening. A significantly higher number of emotional and physical problems were reported by significantly distressed patients. Referrals to psychology and social work services during the pilot study increased, highlighting that screening directed more patients into care. Staff were generally positive about the ability of routine screening to help them care for their patients, and most agreed that some form of routine screening should continue.Conclusion: The use of routine distress screening by inpatient cancer services can significantly improve their capacity to offer psychosocial care.

Stuart J Lee BA(Hons), DPsych · Lynda J Katona BA(Hons), MPsych · Sue E De Bono BA, BSW · Katrina L Lewis RN

Objective: To assess the impact of an 8-week structured mindfulness-based cognitive therapy (MBCT) program on individuals experiencing distress as a consequence of cancer.Design, setting and participants: Prospective study of 16 participants with a history of cancer and five carers of people with cancer recruited from August 2008 to February 2009 through calls to the Cancer Council South Australia Helpline. Participants were assessed for anxiety and depression before and after undergoing a course in MBCT between 30 September and18 November 2008 and 20 February and 10 April 2009.Main outcome measures: Depression, anxiety and mindfulness as measured by the Beck Depression Inventory-II (BDI-II), State–Trait Anxiety Inventory (STAI), and Freiburg Mindfulness Inventory (FMI), respectively, and a consumer-centred evaluation.Results: There were significant reductions in depression (F [1,24] = 6.37; P = 0.012; partial-η 2 = 0.27) and anxiety (F [2,34] = 9.43; P = 0.001, partial-η 2 = 0.36) and mindfulness (F [2,32] = 8.36; P = 0.001; partial-η 2 = 0.34) following the intervention, and these effects were sustained at the 3-month follow-up. Reliable change indices further support these findings. Participants’ scores on measures of depression and anxiety decreased as a function of increased mindfulness, as reflected by significant (P < 0.05) negative correlations between FMI scores and BDI-II scores (ranging from r = − 0.46 to r = − 0.79) and STAI scores (ranging from r = − 0.46 to r = − 0.50) scores at all time points.Conclusion: The MBCT program appears to be an efficacious intervention for use among people affected by cancer who also experience symptoms of depression and anxiety.

Greg R Sharplin BHSc(Hons), BSc · Simeon B W Jones BHSc(Hons), BA · Barbara Hancock DipNurs, DipCouns · Vikki E Knott BA(Hons), PhD · Jacqueline A Bowden MPH, BA(Hons) · Hayley S Whitford PhD

Objective: To test the feasibility and acceptability of a telephone-based program to screen survivors of colorectal cancer (CRC) for distress, and to refer distressed patients to their treating health service.Design, setting and participants: A prospective, multicentre study involving 59 patients with CRC recruited from six public and private health services in Melbourne, Victoria, from 15 June 2008 to 22 September 2009. Patients who had completed adjuvant chemotherapy for CRC were contacted (7–10 days after recruitment [outcall one] and again 4 weeks later [outcall two]) by the Cancer Council Victoria’s helpline nurse, and screened for distress with the Distress and Impact Thermometer (DIT); participants were given tailored information and support and those with distress scores of ≥ 5, and impact scores of ≥ 4, were referred for follow-up. Telephone interviews were conducted 4 weeks after outcall two. Participating helpline and health service staff were surveyed on the feasibility and acceptability of the service.Main outcome measure: Anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS).Results: Of the 59 patients (87%) who agreed to participate, 63% were men; their mean age was 59 years (SD, 9.5 years). HADS depression decreased significantly from baseline (mean score, 4.93; SD, 4.22) to follow-up (mean score, 3.84; SD, 4.10; Z = − 2.375; P = 0.02). However, there was no significant difference in HADS anxiety between baseline (mean score, 5.29; SD, 4.11) and follow-up (mean score, 4.78; SD, 3.65). Outcall one generated two referrals (4% of participants) and outcall two generated four referrals (8%); five of these six participants took up the referrals. Satisfaction with the program among participants was high; 82% found outcall one “quite or very helpful” and 79% found outcall two “quite or very helpful”. Helpline and health service staff reported a straightforward process that did not adversely affect workloads. Conclusion: This model of care carries the potential to meet ongoing psychosocial needs of survivors of CRC.

Patricia M Livingston PhD · Melinda J Craike PhD · Victoria M White PhD · Amanda J Hordern PhD · Michael Jefford MPH, PhD, FRACP · Mari A Botti PhD · Carrie Lethborg PhD · John C Oldroyd PhD

Objectives: To examine 5-year survival from haematological malignancies in children, adolescents and young adults in Australia and determine if there has been any improvement in survival for the older age groups compared with children (the age-related “survival gap”).Design, setting and participants: Population-based study of all Australian children (aged 0–14 years), adolescents (15–19 years) and young adults (20–29 years) diagnosed with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) between 1982 and 2004, with follow-up to 2006.Main outcome measures: 5-year survival from ALL, AML, HL and NHL analysed for four periods of diagnosis (1982–1989, 1990–1994, 1995–1999 and 2000–2004).Results: During 1982–2004, 13 015 people aged ≤ 29 years were diagnosed with primary leukaemia or lymphoma in Australia. For those with ALL, 5-year survival for adolescents improved from 40% (1982–1989) to 74% (2000–2004); the improvement for young adults was smaller (31% to 47%), and both these groups still had lower survival than children, whose 5-year survival improved from 74% to 88%. There was a larger narrowing of the gap for AML: for cases diagnosed in 2000–2004, 5-year survival was similar for young adults (63%), adolescents (74%) and children (69%). For lymphoma cases diagnosed in 2000–2004, 5-year survival in all age groups was greater than 95% for HL and greater than 81% for NHL, although children fared better than adolescents and young adults.Conclusions: These Australian population-based data confirm an improvement in survival from haematological malignancies across all three age groups, but an age-related survival gap remains for adolescents and young adults compared with children, especially for young adults with ALL. Greater participation of adolescents and young adults in clinical trials and more detailed data collection are needed to provide evidence about optimal treatment regimens in these age groups.

Ross Pinkerton MD, FRACP · Rachael-Anne Wills BAppSc(Hons) · Michael D Coory FAFPHM, PhD · Christopher J Fraser MB BS, FRACP, MPH

Neuroendocrine tumours (NETs) are increasing in both incidence and prevalence and, as a group, are more prevalent than either gastric, pancreatic, oesophageal or hepatobiliary adenocarcinomas, or any two of these cancers combined. Clinical awareness of the protean and intermittent symptoms of NETs (eg, sweating, flushing, diarrhoea, and bronchospasm) is critical for timely diagnosis; however, the classical carcinoid syndrome is relatively uncommon. The most useful diagnostic test for gastrointestinal NETs is measurement of plasma chromogranin A (CgA) levels. Disease extent is assessed by both anatomical imaging, and nuclear imaging with radiolabelled somatostatin analogues. Pathological evaluation comprises tumour–node–metastasis classification, a minimum pathological dataset, CgA and synaptophysin immunostaining, as well as mitotic count or Ki-67 index (a marker of cell proliferation) to define grading. Resection of the primary lesion and as much metastatic disease as possible increases the efficacy of medical therapy. Other management strategies include hepatic embolisation and peptide receptor radionuclide therapy. Patients with tumours expressing somatostatin receptors should be treated with somatostatin analogues. Depending on the tumour grade, other effective agents include cytotoxics, tyrosine kinase inhibitors, and antiangiogenics. The overarching requirement for best management of patients with NETs is to ensure that they have ready access to experienced multidisciplinary clinician groups located within centres of appropriate subspecialty expertise.

Irvin M Modlin MD, PhD, DSc · Steven F Moss MB BS, MD, MRCP · Kjell Oberg MD, PhD · Robert Padbury MB BS, PhD, FRACS · Rodney J Hicks MB BS, MD, FRACP · Bjorn I Gustafsson MD, PhD · Nicholas A Wright MD, PhD · Mark Kidd PhD

Greg Mundy was born on 16 June 1942 in Melbourne. Over his career in Australia and the United States, Greg touched the lives of many Australian and US medical graduates. Greg graduated from the University of Melbourne in 1966 and moved with his wife, Helen, to take up a residency at the Royal Hobart Hospital. He immediately stood out as someone destined for leadership in academic medicine. He pursued a doctorate in multiple myeloma under the guidance of Albert Baikie, Professor of Medicine at the University of Tasmania. This probably set the scene for Greg’s continuing interest in the area of bone biology and cancer. After completing his physician training in Hobart, he moved to the US in 1971. Initially, he worked in clinical pharmacology at the University of Rochester, New York, before collaborating with Larry Raisz at the University of Connecticut, Farmington. This laid the foundation for his subsequent career as an international leader in bone biology. In 1980, Greg took up the Chair of the Department of Endocrinology at the University of Texas Health Science Center in San Antonio, establishing a reputation in the top 2% of National Institutes of Health (NIH) awardees. In 2006, Greg was appointed Director of the Center for Bone Biology at Vanderbilt University, Nashville, as John A Oates Chair in Translational Medicine and Professor of Medicine, Pharmacology, Orthopedics and Cancer Biology. He won many prestigious awards from the American Society for Bone and Mineral Research, was President of that Society and of the International Bone and Mineral Society, and also served on several other NIH committees. Greg established OsteoScreen, a successful biotechnology company, in partnership with the University of Texas. He trained more than 150 PhD students from around the world, published over 540 articles, authored 34 patents and developed many international collaborations. Greg was a giant of a man physically and intellectually, but he was a gentle giant. He maintained close ties to Australia and an interest in cricket and football, being an avid Essendon supporter to the end. Despite his extraordinarily frenetic professional life, Greg lived very much for his family — Helen and his children, Gavin, Ben and Jennifer. He died at home on 25 February 2010 after a long fight with a cerebral tumour.

Peter M Brooks · Michael G Loughhead · Allan J McLean