Forum

Alan Coates: an appreciation

William McCarthy

Overview: Progress in cancer control: the Alan Coates effect

Ian H Frazer and Richard F Kefford

Alan Coates and The Cancer Council Australia

Ray Lowenthal

Alan Coates was appointed the inaugural Chief Executive Officer of The Cancer Council Australia (then the Australian Cancer Society) in 1998 and has since amassed achievements in the areas of advocacy, alliances and member services. Under his stewardship, The Cancer Council Australia has become recognised as Australia’s peak non-government cancer control organisation, influencing and guiding national cancer control policy and action. His rare combination of intellect, clinical knowledge, leadership, skilful advocacy and diplomacy has greatly contributed to reducing the burden and impact of cancer in Australia.

“Know your PSA”: not always good advice

Ian F Tannock

Men over the age of 50 are often advised to “know their PSA”, with the implicit assumption that screening for prostate cancer is effective in reducing morbidity and/or mortality. Likewise men who have received local therapy for prostate cancer routinely undergo repeated evaluation of their serum prostate specific antigen (PSA) in order to detect recurrence of disease. Here I suggest that there is no proof that knowledge of PSA improves the average life expectancy, either when used in screening of older men or to detect recurrence of disease. In contrast, there is substantial evidence that knowledge of a raised serum PSA causes substantial anxiety (PSAitis), that it identifies disease in many men that would never have become clinically apparent, and that investigations and treatments initiated because of a raised PSA cause substantial morbidity.

Surgical management of cutaneous melanoma: have we made any real progress in 100 years?

John F Thompson and Helen M Shaw

In the early 20th Century, excision of all primary melanomas with >5cm clearance margins was recommended, with amputation in selected cases – recommendations based on experience of a few patients with locally advanced disease. More recently, randomised trials showed that even thick (>4mm) primary melanomas require no more than 2-3cm clearance and thin (<1mm) and intermediate thickness (1-4mm) melanomas no more than 1-2cm margins to achieve good local control with no adverse effect on survival. The management of regional lymph nodes has also changed on the basis of clinical trial results. Elective node dissection, formerly regarded as necessary, has been abandoned. Today, most patients with intermediate thickness melanomas are offered a “sentinel” node biopsy procedure, with node dissection only if the sentinel node is positive. Sentinel node biopsy provides the most accurate staging and prognostic information currently available and achieves good local control of regional node disease. It may also confer a survival benefit in patients who are node positive but long-term results of clinical trials are awaited to confirm this. In the great majority of patients who present with thin primary melanomas, even sentinel node biopsy is generally considered unnecessary. Although substantial progress has been made over the past 100 years in defining evidence-based surgical management protocols for patients with melanoma, continuing efforts are needed to further improve surgical outcomes in the absence of reliably effective non-surgical therapies.

Mapping the human body: the importance of cross-disciplinary thinking

Andrew Coates ME

The history of scientific thought is marked by spikes of revolutionary thinking, followed by periods of evolutionary consolidation. Both are essential components in the continued development of our understanding. Generally, the revolutionary spikes are instigated by a few (or often one) maverick thinkers who are willing to reassess the conventional wisdom and set out in a new direction. These revolutionary spikes are temporally well spaced, but even during the evolutionary periods, there is a requirement for continual reassessment of the relevancy of other disciplines to one’s own. This paper examines one such example of the combination of disciplines (radiography and geography) that might otherwise be considered disparate and goes on to make some general observations about the importance of such activities, some recommendations for scientists looking to investigate their applicability to their field of expertise.

Melanoma: narrowing the sights on an evasive enemy

Richard F Kefford

Much of the resistance of melanoma to immunotherapy, radiotherapy and cytotoxic treatment is due to an impressive array of molecular defences that derive ultimately from the essential molecular structure of the melanocyte and its biological requirement for defence against apoptosis. The exploration of melanoma susceptibility genes like CDKN2A, CDK4 and MC1R has highlighted a number of key pathways in melanomagenesis. Others have been revealed by a systematic exploration of somatic chromosomal and genetic abnormalities in naevi and melanomas.

Harnessing the immune system to prevent cervical cancer

Ian H Frazer

Cervical cancer can be attributed to infection with a subset of high risk human papillomaviruses. While anogenital human papillomaviruses infection is common, persistence of infection is rare and conveys a significant lifetime risk of anogenital cancer. Vaccines based on human papillomaviruses, like particles produced using recombinant DNA technology, are in late stage clinical trial and are designed to induce neutralising antibody. These vaccines have demonstrated >90% efficacy at preventing persisting high risk human papillomaviruses infection, cervical intraepithelial neoplasia and anogenital warts. They provide a significant addition to strategies to prevent cervical cancer.

The Australia New Zealand Breast Cancer Trials Group: some contributions to breast cancer trials

John F Forbes

The Australian New Zealand Breast Cancer Trials Group was formed in 1978 after the first adjuvant therapy trials were published. This commenced a new era of clinical trials and the commencement of substantial global collaboration, particularly with the International Breast Cancer Study Group. The Australia New Zealand Group is currently conducting 46 trials encompassing prevention and early and advanced disease. In the Australia New Zealand Breast Cancer Trials Group model the elected Board of Directors is responsible for legal and financial affairs, the Scientific Advisory Committee sets the research agenda and the Operations Office is responsible for conduct of the research program. The Australia New Zealand Breast Cancer Trials Group Statistical Centre is contracted out to the National Health and Medical Research Centre Clinical Trials Centre. The Australia New Zealand Group has had peer reviewed research funding (National Health and Medical Research Council) since 1979 and has contributed to more than 400 peer reviewed publications. The research program has always been based on quality science and multidiscipline collaboration. The Breast Cancer Institute of Australia was established to foster education and involvement of consumers in research. Important contributions have already been made by Australia New Zealand Breast Cancer Trials Group researchers to the documented falls in breast cancer mortality and further improvements can be expected from new targeted therapy trials.

Local therapy in a systemic world: the evolution and incarnations of adjuvant radiotherapy for breast cancer

Sue Pendlebury

Alan Coates’ career has seen the evolution of radiotherapy in the adjuvant treatment of breast cancer move from the only modality available, through a period of little utilisation, to its current resurgence amid technology that can provide treatment to regions at risk with little dose delivery to sensitive normal tissues. The results of the early randomised trials reflected poor trial entry procedures, poor dose delivery of the radiotherapy and little accurate targeting of the regions to be treated. Alan was a leader in the era of evidence; if a treatment modality was to be used there must be evidence as to its efficacy. With the development over the last 15 years of high quality machinery and clinical practice that delivers precise radiation doses to areas at risk, the evidence for the role of radiotherapy both in improved survival as well as local control now exists both in the postmastectomy and breast conservation settings.

Antiemetic research: solving patient problems

Ian N Olver

A study which showed that patients ranked nausea and vomiting as their most distressing side-effects of chemotherapy reinforced the need to discover more effective antiemetics. Nausea and vomiting impact on patients’ quality of life. It is important to have patients rank their own adverse experiences and this may differ from an observer’s assessment. A breakthrough in ameliorating acute post chemotherapy emesis occurred with the introduction of the 5 hydroxytryptamine3 antagonists. However, a repeat of patients’ ranking of the severity of side-effects of chemotherapy after the introduction of these drugs still showed nausea and vomiting ranking in the top three. This was due to poor control of delayed emesis, which occurs after 24 hours. A study comparing clinicians’ predictions of the severity of patients’ emesis against their actual experience post chemotherapy showed that clinicians underestimated delayed emesis by up to 28%. The next development in antiemetics was the advent of the neurokinin1 receptor antagonists. When added to ondansetron and dexamethasone the control of delayed emesis was improved by up to 25%. Patients’ experiences of side-effects remains variable. Expectation of nausea for example, can influence the experience of that side-effect. There is a need to repeat a study of patients’ perceptions of toxicity to judge the impact of the triple antiemetic therapy regimens.

On the receiving end: cancer patients’ perceptions of the burden of chemotherapy

Martin HN Tattersall

During the 1970s cancer chemotherapy began to emerge from the research environment of leukaemia and paediatric cancer units to become a part of the management of common cancers occurring in adults. Expectations were high that the successes of chemotherapy in leukaemia and lymphoma would be mirrored in treatment of adult solid tumours. The Sydney branch of the Ludwig Institute for Cancer Research, established at the University of Sydney Royal Prince Alfred Hospital in 1977, reported in 1980 that approximately half the chemotherapy given to adults was palliative in intent and that median life expectancy of those patients was 44 weeks.1 At the time, most chemotherapy was administered to hospitalised patients and the predominant side-effects were nausea, vomiting and alopecia.

Quality of life research that shaped oncologists’ thinking and practice

Martin Stockler

Alan Coates is a pioneer of quality of life research in oncology. This paper reviews three threads in his extensive program of quality of life research that have had enduring influences on how we think about cancer and manage it. The studies produced counterintuitive conclusions to three pragmatic questions: 1) How long should chemotherapy continue in responding patients with advanced cancer? 2) Is baseline quality of life prognostic in people with advanced cancer? 3) What benefits are needed to make adjuvant chemotherapy worthwhile? This research was done predominantly in people with breast cancer and melanoma, but its implications extend to the management of all malignancies.

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