Current Status of Research in Australia Cont.

Discovery Research

In cancer, discovery research, also known as basic research, is the exploration of underlying biological, chemical and physical processes related to cancer induction, growth and treatment responses. This research is undertaken to generate new knowledge with the aim that it may enable the development of new diagnostic and therapeutic techniques. The results of this research sometimes cannot be directly applied to cancer treatment; further translational research is generally required for clinical application.

This research is important, for example to:

1. Improve clinical decision making, e.g. discovery research should be supported to allow studies on associated physiology, genetics or pathology that could add to the clinical picture in the future;
2. Discover and develop technical materials and equipment, allowing improved understanding and characterisation of complex radiation delivery being considered for clinical use;
3. Improve understanding of cellular biology and genetics and their influence on diagnosis and treatment in radiation oncology, leading to the possibility of individualised treatment and incorporation of radiobiology into treatment management;
4. Generate knowledge to be used in the development of targeted therapies for treatment of systemic disease.

Translational Research

To improve human health, scientific discoveries must be translated into practical applications. Such discoveries typically begin at “the bench” with discovery research in which scientists study disease at a molecular or cellular level and then progress to the clinical level, or the patient’s “bedside”⁹. Translational research supports collection of evidence which indicates patient outcomes, shortens the time needed to prove value of treatment before it can be adopted and made available to patients. Typically this involves laboratory or Phase 1 and 2 clinical trials. Successful translational research also provides the basis for making treatments available to patients through Medicare. This applies to radiation oncology as well.

Rapid advances in radiation oncology mean the development of new treatment techniques and technologies to deliver them; Keeping Pace with Radiotherapy Techniques and Technologies explores challenges in evaluating and adopting innovations at the national level. However, survey responses indicate that the adoption of radiation oncology techniques and technologies into patient care in Australia occurs at a limited pace, partly limited by research related factors. These include:

1. Limited access to research expertise in the clinical environment especially in regional and rural facilities;
2. Inadequate access to diagnostic and radiotherapy equipment for research (including clinical trials) purposes;
3. Insufficient staff resources;
4. Lack of availability of translational research funding allocated to radiation oncology;
5. Insufficient interdisciplinary and inter-institutional collaboration.

Despite the challenges of incorporating translational research into the clinical environment, some examples of recent successes in translational research include:

1. The incorporation of ideas from other areas of sciences, for example combining patient images from different imaging modalities including CT/PET/MRI;
2. Development of an MRI Linear Accelerator^10,11;
3. Biologically optimised treatment planning^12-16;
4. Cone beam CT incorporated into the linear accelerator for image guided and adaptive radiotherapy^{17, 18};
5. Adaptive radiotherapy utilizing tumour tracking and response^19,20;
6. Use of tin foil modified electrons to treat superficial cancers²¹;

According to the Cancer Institute NSW, “the translation of research discoveries into public benefit has become a focus for many research funding agencies and is particularly relevant for the Cancer Institute with a core aim of impacting upon population health”²². This view on translational research is shared by Cancer Australia²³, commenting “that the main goal is the uptake of best practice cancer care through the translational research into evidence based information and improvements in cancer control, this includes new models of care that are effective and relevant to the Australian health system and -clinical practice guidance for health professionals and relevant information for patients and the community”. Increased translational research in Australia will allow the assessment and incorporation of the results of discovery research into clinical practice in a more timely and efficient manner than currently occurs.

Implementation Research

Implementation research is the evaluation of new or clinically utilised diagnostic or treatment techniques in the clinical environment. Due to the time delay required to assess some endpoints (such as cancer specific survival), many radiotherapy techniques and technologies are assessed using shorter term endpoints (such as associated toxicity and dosimetry).

Once sufficient evidence is gathered in translational research, the modality or technique can be implemented on a large scale for the benefit of patients. This research is typically conducted through the equivalent of phase 3 and 4 clinical trials. In Australia, these clinical trials are principally conducted through TROG. This research is designed so that the results of translational research become routine and deliver efficient, effective and sustainable patient outcomes.

This research should include areas such as:

1. Early and late treatment toxicities;
2. Quality of life;
3. Survivorship;
4. Evaluation of processes and efficiency;
5. Patient selection for specific treatments.

Successful implementation research may result in infrastructure investment associated with new technology, if it has not already occurred at the translational research stage. In addition, the technique may then attract reimbursement from public funding; one example of this occurring was the radiotherapy treatment verification using electronic portal imaging (EPID).

In the future, the electronic medical record and the minimum radiation oncology data set, linked to the radiotherapy record will allow the equivalent of phase 4 trials to be undertaken. Phase 4 trials are post market surveillance studies. This has the power to improve the personalisation of treatment. Future data collection would allow discovery based research to flow out of these data. For example, genome wide association studies may be able to be performed which could lead to discovery of biomarkers directly relevant to clinical practice. The aim would be to enhance implementation research by linking to future discovery research.

Constraints to Research and Trials

Inadequate funding or lack of dedicated funding and support are the major constraints to radiation oncology research. Although many of the professionals noted during consultation that they participate in research projects in some form, there is a concern that the clinical workload is significant and that available time to do research is minimal. The hospitals are prioritising everyday patient care over research, which is understandable, however in most institutions research is not tangibly recognised as part of core business. The time and resources allocated to research are inadequate and often lack essential administrative or data support.

One of the reasons for the disproportionately low allocation of cancer research funding to radiation oncology may be the challenge in translating a research design that is appropriate for radiation oncology into a form similar to that used in pharmaceutical trials, as this is often the basis for funding applications.

Delays in ethics and governance approvals for multi-site clinical trials lead to delays in recruitment and low engagement. Lack of participation by patients from population sub-groups with poorer outcomes, such as people from regional and rural areas and people from Aboriginal and Torres Strait Islander origin, as well as insufficient resources to support clinical trials at the site level are other challenges restricting research activities.

At the professional level, there are limited opportunities for employment in designated research positions. This is exacerbated by the highly variable and often limited allocation of protected time for research at facility level across all specialties in radiation oncology. Many professionals strongly interested in conducting research feel that they would need to go overseas if they want a prominent career in research. The situation presents an even greater challenge in regional and rural facilities where maintaining appropriate staffing levels can be difficult. Additional full time equivalent (FTE) positions or effective management of existing workforce to ensure that protected research time is recognised and made available would be a solution to this challenge.

Limited access to radiation oncology equipment can constrain research initiatives. Flexible hours (i.e. outside of patient treatment times) and protected time on the equipment or dedicated research equipment (such as linacs, planned on a national level) need to be planned. With any purchase of radiation oncology equipment, the utilization of that equipment should be planned such that provisions for patient treatment, research access, as well as maintenance and quality assurance are included within operating hours. These factors should also be considered in service planning and reporting.

A constraint to implementational and some translational research is that there are commercial-in-confidence considerations for manufacturers of radiotherapy equipment. There is a perceived risk that competitors may use research results to support similarly designed products without the associated research investment.

A strong focus is needed on leadership and fostering collaboration between disciplines and organisations and international collaboration. At present, the academic, research and clinical components continue to function as disconnected silos. Often, radiotherapy research in Australia is conducted in isolation and as a result it takes longer for research projects to generate meaningful data sets, reducing the academic impact of the work. International collaboration with sector partners would make research activities increasingly financially viable and give better client participation with access to larger populations.

Academia and Education

Initial education for all radiation oncology professions is provided in universities and is supplemented with a mandatory clinical training program delivered either within the degree program, or following graduation. Specialised education and training as well as continuing professional development (CPD), is governed, administered, and in part provided by the professional associations often in collaboration with universities and facilities. Academia refers to both the universities and the professional associations.

Training for all radiation oncology professions has a clinical component aligned with current clinical practice. There is also a requirement for a research component for most programs. There is a link between providing education in research in an academic environment and practicing it in a clinical environment. Supporting this link is particularly important for those professionals whose exposure to research in their education and training is limited.

It is equally important for contemporary clinical practice to be continuously incorporated into education and training programs for the radiation oncology professions as this ensures that trainees have the necessary knowledge to work effectively. The links between the academic and clinical environments are important as they enable the education of quality trainees, the enhancement of research capability, and the implementation of techniques and technologies for the benefit of patients.