Cancer Council Australia, Sydney, New South Wales
The 40th anniversary of the Clinical Oncological Society of Australia (COSA) is a milestone for the society itself and to the many aspects of cancer control to which society members both contribute and continue to promote in Australia.
Forty years ago cancer control in a clinical sense was a relatively unconsidered entity. Patients consulted their local doctors who frequently oversaw their total management. There were few clinicians other than radiotherapists who were considered to be cancer doctors. Once patients were referred to a specialist, that clinician frequently looked to the care of the patient thereafter, and continued until absolutely nothing more could be done. This was the practice pattern and it limited patient care. There were few institutions dedicated to delivering active cancer care while cancer was still treatable; there was a general sense of patient ownership by clinicians. Within the referral process, patients often had to make appointments far from home. These were negotiated appointments and meant frequent treks between doctors’ rooms. Patients frequently had to meet heavy economic demands.
To be fair, governments were aware of cancer and contributed to funding of education at public and professional levels, but individual patients and their families were often bewildered in this area and felt short-changed during the course of their management and at what they felt were unsatisfactory outcomes.
However, changes occurred as they always do and there were strong minds and hearts belonging to skilful people who began to look more carefully at how cancer could be better controlled and managed. There were small groups exploring the way ahead, as new findings in cancer control and as new patterns of care were acknowledged. One such group became COSA.
COSA owes a great deal to three of its founders. Brian Fleming, a head and neck surgeon in Melbourne, had observed what was happening in the cancer arena overseas and thought it should happen here. Together with Leicester Atkinson, an English trained radiotherapist who was striving for more modern equipment, and Robert Melville, a Sydney surgeon interested delivering care in breast cancer. They gathered some like-minded people to start to address the issues facing cancer control. COSA became a reality in 1973, with Brian Fleming as its President. He was succeeded in turn by Atkinson and Melville. The first two presidents each had three years to ensure stability and since then a two year presidency has seen steady longitudinal and additive growth. The first medical oncologist and total academic was Martin Tattersall, who became President in November 1981. These early leaders have been followed by distinguished and skilful clinicians who have covered the spectrum of modern day skills in cancer control (table 1).
The Presidents have been assisted in pursuing their goals by dedicated staff, initially by Lawrie Wright, who helped effectively establish and promote the Association. In 2003 Margaret McJannett became Executive Officer. Through her generosity and management skills she adopted changes and incorporated advances as they developed. These moves cemented COSA as a leader in cancer control. She and her staff established a succession which works closely with all elements of COSA to ensure success across Australia.
No less than 27 groups have since joined COSA, with experimental oncology and head and neck leading in 1973, breast in 1974, and the remaining groups joining in an orderly fashion over time, and this is likely to continue. The significant input of nursing and psychosocial groups adds to COSA’s lustre and an inexhaustible future.
The forming of the individual groups (table 2) reveals the dates of their commencement and acts as a strong indicator of how individuals had made the decision to develop special skills and no longer work in isolation. Multidisciplinary groups interested in cancer care were aborning.
These observations and the reality of the strength shown in the annual COSA meeting every November demonstrates that the truth and strength derived from association of focused minds are not evanescent.
This special issue of Cancer Forum acknowledges the 40 years of COSA and addresses a number of areas relevant to cancer control and how they are being impacted by wider cooperation and broadening of minds towards management of malignancy.
I have enjoyed the opportunity to pay deference to this special association which is rather unique in the Australian scene.
A wide range of endeavours is represented and the health of each segment, as expressed through leaders in each field, is self-evident. It was determined that the common cancers should be short presentations in the interest of the length of the issue.
The presentation has been broken into four parts to represent COSA’s activities – the patient, craft based, specific cancers and applied sciences. Each paper addresses a special subject and is complete in itself. While there will be some overlapping, all are directed at an element of cancer control.
The many faces of prevention in the practice of oncology – each a challenge to the clinician
Zucca et al outline that prevention in oncology is usually addressed towards progression of treated cancer or development of new cancer.1 The authors promote prevention in a holistic scenario.2 This approach features the prevention of suffering and the maintaining of quality of life. The health professionals in the cancer team are encouraged to promote healthy lifestyles for patients and for the relatives for whom the patients’ cancer (the patient and the cancer) pose risk.
The paper is presented in three parts and will reward those who read it in its entirety.
Patients play a part in their own care
Luxford makes the unambiguous observation that patients are entitled to receive respect and understanding of their values and preferences, established through courtesy, communication and trust.6 COSA has been a catalyst in promoting comprehensive approaches involving individuals in their own care, but also in research, governance and policy. COSA has worked with a number of groups promoting consumer involvement in clinical cancer research through “increased training, mentoring and collaboration across the 14 cancer cooperative trials groups”. The paper summarises the moves to rise above the ‘disease-based’ model of care and recognises that acceptance of evidence is upon us. In summarising consumer involvement, ‘nothing about me without me’.
Psychosocial aspects of delivery oncology care: an update – a win-win situation
Butow et al present a paper clearly stating the factors faced by oncology patients in relation to their psychosocial needs in the broad generality of their lives, and also the effects on those around them when being presented with a diagnosis of life threatening disease.7–9
The practice of psychosocial care became established in the 20th century, but psycho-oncology emerged as a defined discipline only 40 years ago. The first psycho-oncology interest group in Australia was established within COSA in 1996 and merged with (PoPoG) in 2004 as one of the country’s 14 national cancer trial groups.
Australia’s cancer researchers and consumers have joined to advance the field and together with many organisations have produced evidence-based guidelines for psychosocial care of women with breast cancer and adults with cancer.10 These researchers have demonstrated that communication between health professionals and patients is a crucial element of quality health care despite being a challenge to all groups. In Australia, patients expect effective communication with their doctor and the opportunity to do so.
Downsides occur when patients are dissatisfied with communication; noncooperation or compliance and reversion to alternative medicines are important elements of failure. These trends have been clearly observed and Butow et al point to Australian randomised control trials, as being the first in the field.7 Trials have been extended to involve supportive care/psycho-educational interventions that are clinically feasible and can be demonstrated on strong evidence to have a positive impact on patients.10
The authors also observe that some patients live longer and are ‘survivors’.11 Their special needs are being addressed across Australia with the November 2012 COSA approved formation of a survivorship group, from which it is certain high level evidence-based knowledge will emerge to aid clinical carers.4 Interventions, will undoubtedly flow and supplement cancer plans and priorities among psychosocial researchers. It is clear that Australia has now placed its own indelible mark on the cancer agenda in relation to psycho-oncological and survivorship issues.
Medical and psychosocial challenges in caring for adolescent and young adult patients with cancer
Anazodo and Chard are reporting on a very young speciality and address both clinical and healthcare delivery matters.12 Adolescent and young adult (AYA) patients with cancer are categorised as being between 15 and 25 years of age. The authors note that people in this age range have needs that differ from both younger children and adults, and are entitled to receive specialised services.13–15
People with lower socioeconomic status have lower five year survival than those living in areas of higher economic status (90% v 85%) and are 1.3 times more likely to die if they live outside a big city. There is lack of improvement in survival figures between children and AYAs (survival gap) in specified tumour groups; this causes great concern among both professionals and carers and is not yet explained.
The authors are limited in providing reasons for lower survival rates, but outline a range of suggestions for study, including RCTs which are to be encouraged; tissue banking outlined in this group of papers should not be overlooked.16–18
Psychosocial aspects are better developed and distress (a spectrum of clinical conditions from sadness and fear to depression and anxiety) is an area that should attract attention of all cancer healthcare workers.19 CanTeen’s psychosocial screening tool to guide psychological assessments has been in use in youth cancer services since May 2011. It is planned to validate this tool in international studies and it may be the key to better outcomes. Government has recognised the validity of this infant speciality and in 2010 provided CanTeen with supporting finance to administer the Youth Cancer Networks Program leading to provision of services in mainland Australia. The effectiveness of this program is undergoing implementation research to ensure an evidence base. The issues that involve survivorship have been covered extensively in Cancer Forum,20,21 but further research in assessing and advising survivors has high priority. Fertility preservation, early diagnosis and better assessment has been guaranteed by COSA and CanTeen. Specialisation at this early stage with a special oncology certificate in Adolescent Health and Welfare, was created at the University of Melbourne in 2011.
Their care – our inheritance [healthcare of Indigenous people]
Condon et al’s paper is a challenge to our hearts and minds.22 Our hearts are easily in place with doing something to alleviate the problems outlined. Our minds have produced numerous approaches and extremely laudable work from dedicated people. Governments have given money and acronym-based management groups, but despite Reconciliation have yet to find ‘can do’ in the minds of all the populace, both Australian and Indigenous people.
After 225 years, Australia is a country where Indigenous people have a lower incidence of cancer than non-Indigenous people, but their prognosis is poorer. This most often is because diagnosis is later or too late. Furthermore, it is unfortunate that indigenous people often do not live as long as the remainder of the population and this may accentuate what appear to be poorer outcomes of treatment. Patients may contribute to the cancer through their toxic lifestyle and are less likely to receive complete or curative treatment than non-Indigenous Australians, “particularly in the first year after diagnosis”.
The paper identifies that Indigenous people have some protective factors eg. greater levels of melanin in skin, earlier age pregnancy and longer breast feeding, whereas lower participation in cancer screening, higher prevalence of hepatitis B and higher risk of smoking are adverse factors. Smoking is “the single most” damaging risk factor for cancer and many other health problems.
A good report on significant reduction in smoking has been recorded recently and state Governments and anti-tobacco groups have had significant effect, yet 47.7% of Indigenous people aged 18 and over still smoke.23 It is important that governments and advocates continue to be supporters of anti-smoking programs.
Screening programs need encouragement in carefully planned approaches; maybe one cancer at a time would be worth trying. Teams need training and greater exposure of medical students to elective term research through good mentors and sound advisors; this approach might widen the committed pool required. I certainly observed strong interest in indigenous health by medical undergraduates when I was at James Cook University Medical School last year.
The National Health and Medical Research Council has established studies to discover indigenous strategies to improve cancer outcomes via engagement, research, translation and training (DISCOVER-TT). An educational network for practitioners, policy makers and researchers, the National Indigenous Cancer Network is being established through the Menzies School in Darwin and appropriate institutions to learn more about cancer in Indigenous people.
Primary care providers and specialists join together in patient care
Jiwa, McManus and Dadich make a strong observation that primary care in Australia is “well positioned to support individuals diagnosed with cancer and their caretakers.”5 Primary care providers have a number of impediments to address and overcome if they are to provide optimal quality and continuity of care. The authors performed a review of research available in this area and identified a paucity of evidence-based knowledge of practice, a hiatus that clearly needs to be addressed. Recommendations address the areas of deficiency and make persuasive suggestions for primary care providers involvement following specialists treatments and strategies, and for continuity of care to be planned before patient discharge.
Forty years of nursing in Australia – the emergence of a specialty
Yates and Aranda record the dramatic changes that have occurred in nursing in Australia from that of 40 years ago.24 While all areas in cancer care have experienced progress, perhaps nursing has incorporated more changes than any of those in health care over this period would have envisaged.
When the Government decided to move all nurse training from hospitals to universities in the 1980s, there were fiery discussions on the pros and cons of the magnitude of the changes. The Government was right. Nursing training was reset and became homogeneous over Australia by the time transfer was completed in 1944, in spite of those who denied change could happen in Australia.
Once there was a single entry required for practice as a registered nurse. The opportunity for nurses to advance through university-based processes of masters and doctorate degrees was a new beginning. Now nurses in special areas have defined their special needs and embarked on specialisation in various areas. For instance, nurses with a special interest in cancer have transited through COSA and, while maintaining strong links with the society have established the Cancer Nurses Society.
While being highly specialised, being a nurse conjures up strong images in the eyes of patients; maintaining a ‘nurse’ image will not detract in any way from the nurses ambition of fulfilling important specialist roles.
Papers by Butow, Koh, Luxford and Zucca carry strong messages for nurses, and indeed all health workers, to adopt supportive and innovative approaches to care which strengthen the capacity of patients to be involved in their own care.1,6,7,25 Such processes will strengthen patients’ capacity for involvement in their own management and make for better multidisciplinary, professional and inter-professional interaction and patient satisfaction.
Nurses will have significant opportunities to ensure that patients receive optimal pain relief. Other papers refer to unrelieved pain, 26,27 which could be an area where cancer nurses working with palliative care teams can help eliminate judgemental assessment once appropriate distractors are eliminated and pain relief administered.1
The nursing odyssey is another good news story in cancer care.
Evolution of palliative care in Australia 1973-2013 – an icon for compassionate care
Currow and Phillips relate the background of the development of palliative care in Australia and its association with the development of oncology services.28 They take into account the continuous development of sub-specialist groups in oncology. Early on, services for the dying were initially directed at the poor and the dying and included problems beyond cancer care. Initially, there were three major service groups and there were also smaller groups in suburbs and towns, mostly under religious operators. In most local areas, there were dedicated nursing staff who took care of these patients, usually assisted by local GPs. There were no formal discharge policies and as a consequence, patient numbers grew in spite of the nature of the facility.
The authors outline the changes that led to the important step to bring palliative care into existing health services, so hospices closed. Although not all agreed with the model developed by the Webster Committee,29 it prevailed, and has been very successful. Its spread was aided in no little part by associating with health care groups already interested to support palliative care: oncology primary care, anaesthesia, pain medicine, general medicine, geriatrics and psychiatry. Each of these specialties had their champions and contributed to progress on the basis that they would assist development of processes directed at ameliorating the lot of patients requiring palliative care services and their families. Government support in relation to Medicare agreements has increased service and increased geographical access.
National funding has also assisted research, much of it being at category 1 level. Research sources and access to evidence has been nationally facilitated.
The authors acknowledge and encourage efforts to get a handle on drugs traditionally used, but not proven effective by a range of phase III trials. Quality of care meeting benchmarks and review is a constant feature of palliative unit activity.
It is pleasing to see two iconic peers in the field in Australia recognised for their persistence and early success, the late Wally Moon and Fred Gunz. Fred himself lent on Cancer Society of Australia and COSA early in the piece to promote a palliative mind set.
Importantly, undergraduate education to entrench the overall skills required in palliative care as a part of medicine, and the outreach to ensure all graduates can engage and plug into a program which seamlessly enhances the essential dignity of patients and their care and totally frees them of pain, is a continuum commencing when appropriate to patients needs and not just seen as a terminal endeavour.1
Radiotherapy a miracle of cooperative ingenuity
Kenny et al in their well stated paper, fully justify the avant-garde title.30 The authors strongly support the role radiotherapy contributes to integrated cancer care as now practised. The advances in the field would, it is thought, more than fulfil the aspirations of 40 years ago. They restate their credo that delivery of radiation therapy “is, always has been, and always will be” to treat cancer tissue and spare normal tissue at a maximal level. Progress has required massive organisation of technological resources and skilful integration with all elements of cancer care. Its importance in the cancer field far exceeds that of 40 years ago. Radiation oncology requires the near perfect symbiosis of basic scientific research, bioengineering and nuclear physics, combined with the highest level of oncology, medical and radiological training.
As essayed for the reader, radiation care is an example of what science can do when appropriately integrated into cancer care. Every component of this paper deserves special attention.
Aside: The only equivalent to collating all these technological resources was seen in the development of the atom bomb and demonstrates that some good can come from horrendous events.
Surgery becomes multidisciplinary
This paper stresses the need for strong support from surgery in areas where it has been regarded as the mainstay of cancer treatment for centuries, and where it still remains a central component of cancer management. Mann et al discuss the key elements of changes in surgery that have occurred during the last 40 years.31 They also encourage speculation on future changes. It is clearly noted that surgeons and surgery no longer stand alone and have shown leadership and flexibility in becoming involved in multi-disciplinary care. Surgeons have shown that in a multidisciplinary approach with committed expert personnel, together with multiple care modalities and where necessary, special technology can be vital to sound surgical practice. Sound decision making can lead to better selection of care and better and safer outcomes which boost current expectations, particularly when patients are involved in the planning process.
The surgeon’s approach to screening and early detection of malignant lesions are of importance in reducing the magnitude, deformity and disability which hitherto confronted patients after heroic or extended surgery. It is questioned as to whether or not some of this surgery was appropriate. Further challenges will, it is assumed, lead to a greater role for neo-adjuvant therapy in reducing the extent to which surgery is required in patient care.
Screening: a critical process for clinical practice
Penman discusses screening and addresses areas of success and areas where physician alertness needs to be maintained. He urges the development of guidelines that will catalyse physician motivation to appreciate the value of screening and early detection, and to optimise the response by taking notice of the results.32 COSA itself was born as efforts to screen for cancer were being pioneered, its particular effort being directed to the breast, an area of limited evidence at that time. Nor was time lost in promoting education on ‘the seven warning signs of cancer’ promulgated by the American Cancer Society.33
Screening has not been a subject of plain sailing, but mass cancer screening endorsed by clinicians and cancer bodies can have a salutary effect on demonstrating reduction of mortality and interval cancer rates. Physicians and patients of course, are interested in the results of individuals, particularly those that relate to themselves. The paper addresses the range of current screening activities and particular reference is made to hepatocellular cancer. This demands the attention of us all and support for local efforts is important.34,35
Breast cancer – the change to chronic disease
Breast cancer has clearly been and remains the foremost malignancy in the public eye. Coates explains the breadth of change in its diagnosis and management and what a difference 40 years can make.36 No longer is the most massive surgical procedure a mark of capable management, and the move of diagnosis from palpability and possible spread of cancer to radiologically diagnosed minimal malignancy has been beneficial. Breast reconstruction has led to greater personal esteem as body image is restored. Endocrine and drug therapies are now better tailored and effective, while molecular therapy targeting specific molecular changes represents an exciting and possibly minimalist approach in some patients.
Attention to the patient’s quality of life and self-evaluation closes a deep gap from the past.25 The growth of breast caring supportive staff has significantly reduced patient anxiety. The Australia-wide support and conduct of clinical trials is now expected rather than doubted, and has strong patient and consumer advocates.37 Cancer of the breast is now more effectively treated and has an increasing survival rate.
Prostate cancer – exciting news for men
Prostatic cancer is the most common non-skin malignancy and a frequent cause of death in men. In this paper, Davis et all endorse that most men diagnosed with prostate cancer have localised disease and that prostatectomy or radical radiotherapy, in spite of a range of morbidities, have excellent cancer treatment outcomes.38 Relapsed or metastatic disease is treatable, but leads to the lethal form of disease, metastatic castrate-resistant prostate cancer (mCRPC) over variable lengths of time. Docetaxel was introduced 10 years ago and new treatments, which only became available in the last two-three years, are showing benefit. All depend on an understanding the unique biology of prostate cancer and recognising of the important place played by signalling through the androgen receptor axis, which is still critical in many instances in mCRPC, even when androgen deprivation or receptor blockade have already failed.39 Among many positives is the development of a new generation of androgen receptor antagonists. A new cytotoxic drug, Carbazitaxel, is effective and is allowed for use and for reimbursed for mCRPC post-docetaxel. Bone therapy has been expanded as targeted therapy with radium 223 chloride. Effective immunotherapy has shown advantage and is being extensively trialled in mCRPC.16
Image-guided and robotic ablative surgery are being investigated. Imaging and its role in underpinning clinical confidence is discussed. The demand of each man with mCRPC to have tailored supportive treatment is endorsed. The authors’ encouragement for excitement in the new therapeutic targets to increase the benefits for men with mCRPC is inimical to better understanding the biology of this difficult disease, which should be of assistance to both clinicians and patients and lead hopefully to better outcomes.
Colorectal cancer – an exemplar of clinician cooperation
Over the last 40 years, the range of care of this common cancer has been a notable success for Australian clinicians and patients, particularly those contributing through local trial groups. COSA’s role in facilitating research, education and multidisciplinary interaction in an academic environment has further improved patient care. This broad spectrum of study, education, prevention and best clinical care is well stated in Segelov’s contribution.18 The additional role of COSA in supporting screening from its beginning, before becoming government funded (National Bowel Cancer Screening Program) is worthy of particular notice. More sophisticated diagnostic evaluation by MRI is now the standard of care. Another significant method of diagnosis, with PET and CT scanning, has led to better selection of patients with liver metastases who are suitable for appropriate hepatic resection. Australian and New Zealand surgeons have contributed to proving laparoscopic equivalence with open surgery (ALCCaS study) and are continuing trials with AGTIG (Australasian Gastro-Intestinal Group) (a la carte).
The importance of quality training for colorectal surgery, while at the same time promoting appropriate surgery for liver and lung metastases, has been clearly demonstrated. The value of multidisciplinary teams in these areas of progress together with chemotherapy, radiation therapy and psychosocial and survivor support underlies the strong moves that are being realised in personalised medicine. This needs to be built on better understanding of the genetic and molecular elements of the cell.16 The results of these efforts will be able to be translated to rural and regional centres and countries beyond our shores.
Lung cancer – a continuing challenge and a public health victory
Survival for lung cancer continues to be among the worst for any cancer. Ball outlines the quintessential problems that have faced those treating lung cancer over the last 40 years.40 It is noted that a nihilistic trial in 1971 discouraged and delayed active treatment of the disease and this view continued for some years.41
A most important advance however, resulted from public health advocacy and the active anti-tobacco campaigns, which have resulted in a fall in mortality from lung cancer. The public health campaign continues to gain acceptance and strength.
In 1973, stage and performance status were recognised as critical prognostic factors and CT screening of the chest was adopted in staging and radiotherapy planning.42 Each decade since 1970 has been marked by a significantly strong research effort and been rewarded with an improvement in outcomes resulting from newer therapeutic approaches, and confirmation that lung cancer can be detected earlier by CT scanning. Both small cell lung cancer and non-small cell lung cancer require well directed and continuing research, to identify the best of many strategies available.
Haematological malignancies – showing the way in oncology
Bishop notes that the treatment of haematological malignancies introduced systemic treatment and combination therapy and reduction of either the need for or the extent of radiotherapy.43
These agents blazed a trail for oncology to follow. Although Paul Ehrlich was first to use the term ‘chemotherapy’, its human use was hastened by a very serious and serendipitous affair in war. It was serendipitous on two accounts, first the sinking of the liberty ship John Harvey in a Luftwaffe raid in Bari Harbour in Italy on 2nd December 1943. The ship was carrying a secret cargo of 2000 M47A1 mustard gas bombs, to be used if Germany used mustard gas as it had threatened in Italy. On sinking, the liquid sulphur mustard spilled into the water. The second serendipitous fact was that the water was contaminated by oil spilled from the damaged ships. The sailors who had abandoned their ships and became smeared with oil, an effective solvent for sulphur mustard. On triage, those damaged by blast and fire were treated and the oil smeared sailors were not given priority attention; sailors and hundreds of civilians were poisoned by a gaseous cloud of sulphur mustard vapour. The incident was kept secret by the military, but bone marrow failure led to a wider medical investigation and to the first chemotherapy drug, mustine. In a sense, these two serendipitous events led to an enormous breakthrough in medical care and set the scene for the birth of oncology.44
The author addresses the progress made in the areas of lymphoma and leukaemia and includes mention of the move towards personalised or precision therapy.16 The development of tyrosine-kinase inhibitor drugs introduces the possibility that they may have use as targeted therapies,16 and also be effective in other malignancies than chronic myeloid leukaemia. The importance of allogenic haemopoietic cell transplantation remains as a durable way to eradicate chronic myeloid leukaemia. Monoclonal antibody development has played a significant part in therapeutic plans, some in association with other systemic drugs. Genetic studies and treatment may be of greater use as they draw on genomic resources.
A possible obstacle to progress in the general field of cancer arises as more defined subsets of malignancies indicate the challenges these create for large scale and clearly necessary clinical trials.
Melanoma – the nemesis of sunshine…
Thompson and Menzies make a clear statement on melanoma as at 40 years ago and pay appropriate respect to the efforts of two Australians, the late Gerald Milton and Neville Davis, who led the world in establishing dedicated melanoma treatment centres.45 The recognition of Oliver Lancaster’s epidemiological research revealing exposure to solar ultraviolet radiation in melanoma genesis, marked a huge Australian contribution to leading the charge on melanoma clinically.46 Breslow thickness of melanoma is recorded as the principal indicator of outcome, while indicating that ulceration and mitotic rate are significant factors. The Breslow thickness is discussed in relation to surgical clearance of lesions. In lesions 1-4mm thick, the sentinel node has, on the basis of interim trial (MSLT-1) results, provided accurate staging and substantial survival advantage if lymphadenectomy is performed when found to be positive.47 This trial has significant Australian input and the final analysis is expected in the middle of this year.
Increased understanding of molecular biology and immune regulation are continually changing systemic treatments to patients’ advantage and research continues. Immunological therapies in melanoma and their effects are described, but most including antibodies are under trial at present. Melanoma persists as a serious problem in Australia and is increasing worldwide. Multidisciplinary trials will play an important part in research at basic and clinical level. The development and contribution to well-planned trials continues to be an imperative if more definitive therapy is to be achieved.
Tissue banking and its role in clinical and biological advances in oncology – a reservoir for future research
Gundara and Sidhu point to clinical and translational aspects of oncology and their exponential advancement over 40 years.17 The laboratory, “where rigorous scientific study of the biological milieu that is neoplasia has been undertaken,” is responsible for much of the progress that has paralleled advancement in informational technology systems and mathematical modelling facility in both in vitro and in vivo tissue experimentation. It is a given that cancer clinicians know that understanding of cancer can be derived from asking questions of cancer in human tissue samples.
This process is a benefit derived from tissue banking, where tissue deposits yield material from study and provision of information to researchers. The authors refer to the history of this enlightened activity by Rudolf Klen in 1952, and while initially only cadaver tissue was banked, it has now expanded to involve living donor tissue.48 It is important that all clinical oncologists be aware of best quality of care and the ethics that relate to tissue banks and medical registries. The clinical responsibility towards patients are imperatives to be noted, understood and acted upon.49,50
The authors refer to their own units’ tissue bank and point to its value in stimulating international cooperation, especially when the cancer is rare.51,52 Electronic records will assist further in advancing translational research hubs and assist in linking tissue and clinical data.
These factors are impacted in the age of personalised medicine, which is riding on the back of tissue banks and laboratories that are researching new methods and standards of diagnosis.12,16,18,53 They also allow review of old material at appropriate times.
Optimising tissue bank collection of clinical tissue and other appropriate body elements has been achieved in some sites.54 This requires that all cancer clinicians develop a prospective mindset to ensure materials are ethically collected, promote a bedside bench to and return to bedside attitude in practice and training, embracing the full force of demands as outlined in the authors’ ‘call to arms’.
Targeted therapies, aspects of pharmaceutical and oncological management
Brown and Burdett have submitted a comprehensive paper on targeted therapy, which is a new and complex subject.16 Surgery, radiotherapy and chemotherapy are the established modalities of cancer treatment. The authors suggest that immunotherapy is ready to be included as the fourth pillar of standard cancer therapy.
Each element of this paper conveys a clear message to the reader and carefully guides interpretation. Definition of the subject is clearly essayed. The aim of personalised cancer medicine is to deliver the right drug to the right person at the right time. However, there are distractors which, it is indicated, may not always allow for choosing the right drug, right cancer or right person. The scope of targeted therapy is to encompass “the complex biology intrinsic to most cancers”. While the aim to find the right target can be a protracted and difficult exercise, identifying an appropriate target mutation can be evident to the receptive researcher/clinician.
The Medical Benefits Schedule now reimburses the cost of genetic tests to allow determining use of targeted cancer therapies. While this will hasten research, challenges to drug access and reimbursement will still be hurdles to jump to achieve truly personalised cancer medicine.
The benefits of being on target are well outlined, and the importance of being well acquainted with the tumour biology and becoming aware of newer and emerging investigative tools such as functional cancer imaging should excite us all. The final sentences in the paper should encourage clinicians and researchers of all generations.
“Therefore work on providing electronic point of care services may help to mitigate the risks of polypharmacy. Ultimately however, the targeted therapies boom will oblige clinical oncology professionals to obtain new skills to control cancer.”
This paper was an exciting primer and will encourage clinicians to maintain close surveillance of the new literature as it appears, so that their cancer patients can receive the full measure of care.
Randomised clinical trials the core of the future in clinical practice
Over the last 40 years there has been a strong move to, where possible, incorporate evidence-base in medical practice. In most areas of practice, evidence is accrued through randomised clinical trials (RCTs). Sjoquist and Zalcberg support this approach and outline various aspects of the process to achieve their titled outcome.37
Establishing trials that are both recognised and trusted involves a wide range of tools that are to be embraced by developers of RCTs, whether they are based on an individual investigation or cooperative group. Initially, safety and efficacy of the tool chosen to answer the question, together with the special elements of psychological support, palliation and outcome, are expected by patients and their significant others. These factors must be addressed during the trial if patients are to accept the findings. Patients must be strong contributors to the trials process.
The authors outline some specific successes and make the point that in Australia, enthusiasm and collaboration have resulted in cooperative trial groups, which from the time of developing each trial makes literally enormous demands on all members of the trial group. They are unable to relax in their role without adversely affecting others who must “pick up the ball” for them. Seeing any trial through from concept to finalisation and presenting results in acceptable form can take focused effort over a period of years.
Investigator initiated trials have found significant trust as against industry sponsored trials.55 The investigator initiated trials must appear substantiated by evidence at every point to retain accolades and trust and the question asked must be seen as relevant by peers. These characteristics also apply to cancer cooperative trials groups and must exercise the minds of trial developers in selecting collaborators who can stay the distance. Australian trials groups have been rigorous in design and personnel and patient selection.
The importance of RCTs being biologically appropriate, readily interpreted, clinician accepted and having regulatory approval, means all have met high standards. Some barriers to trials development persist in relation to funding, total signing off of the nationwide ethics approval system, trials design and time involved by collaborators. These areas all continue to be evaluated.
There have been appropriate suggestions that the Pharmaceutical Benefits Scheme should consider funding local drug trials evaluation before listing. This seems a reasonable request. The careful planning and balance of Australian trials have received high recognition. The interest in trials is reflected in the Primary Care Collaborative Cancer Clinical Trials Group (PC4) founded in 2009; it has received many concepts and 34 are under development.
RCTs open the way to develop pathways to tolerable and less demanding care.
Outcomes are important in oncology – what patients expect
Patients have an interest in the outcome of their proposed management from the time they receive a firm diagnosis. Historically, mortality, survival and recurrence rates of cancer have been major factors in decision making, particularly as seen by the clinician. Koh et al report that significant change has occurred, with emphasis being placed on patient reported outcomes being seen as important both in research and clinical practice.25 Patient reported outcomes are any outcome measures reported by patients without interference or interpretation by any health care professional. The outcomes as perceived by the patient are often intangible to other people and so they are clearly complementary to traditional outcome measures.
Patients also show significant interest in their quality of life; the specifics of measuring quality of life are discussed in relation to health. Health related quality of life measurement needs to be relevant to the condition under care and each measure validated, as patient specific measures allow choice of outcome. Such an approach generates growth in the number of measuring instruments and commercial databases to assist in identifying health related quality of life, but costs are involved in the measuring and repetitive processing of patient preference and decision making. These areas are still in the research field and the level of literacy to allow their valid use is still not clear.
The authors address cost-effectiveness against a range of health costs as a percentage of GDP, from 4.1% in the Netherlands, to 16% in the US, to 8.4% in Australia. The approach towards 20% present political challenges. Despite differing costs, life expectancy and cancer outcomes are similar in all these countries. High cost drugs and their benefits, and whether there is fairness if money limits are capped, are matters under investigation.56,57 Patient reported outcomes are becoming a feature of RCTs, but the uptake is slow.
The goal in patient reported outcomes research is to have the knowledge incorporated into practice and improve patient care and clinician capacity. Health related quality of life feedback to clinicians is invaluable in care and understanding of survivorship. If a financial incentive to collect data is effective, it should be pursued to the benefit of patients and perhaps survival of intelligence and favoured carers for future studies.