Towards personalised cancer treatment

Wai Lup Wong,  Consultant Radiologist Mount-Vernon Hospital London.

In 2011, it is impossible to consider the modern management of cancer without including PET-CT. The article reviews the up-to date role of PET-CT in oncology practice and considers current areas of PET-CT research that will directly impact on care of cancer patients.

In 1898, Roentgen discovered  X-rays. It gave birth to medical imaging which has revolutionised the care of cancer patients. In 2011, it is impossible to imagine delivery of cancer care without medical imaging. A direct and advanced application of the Nobel Prize laureate’s discovery is Positron Emission-Computed Tomography (PET-CT). Hailed as invention of the year by Time magazine in 2000, it is one of the main tools of contemporary cancer imaging.

Derangement in chemical processes is the first indicator of cancer and it precedes changes in cellular structure. PET-CT provides unique information about metabolic or chemical processes within cells and precisely identifies where these malign processes are occurring within in the body.

Cancers have increased glucose metabolism compared with normal tissue. 18F-fluro deoxyglucose (FDG) PET-CT demonstrates this difference between normal and cancer cells and is the most sensitive test for diagnosing cancer.

FDG PET-CT impacts on all steps of a patient’s cancer journey. Appropriate initial treatment of cancer hinges on accurate diagnosis of where the cancer originates from in the body, or in other words determination of the primary site of the malignant tumour, and precise delineation of extent of spread of cancer or establishment of stage of disease.

The primary site is normally confirmed by clinical assessment complimented by usual imaging and biopsy. There are occasions when the primary site is not apparent on usual assessment and in these cases, FDG PET-CT is contributory. The typical clinical scenario is the patient who presents with cancerous nodes in the neck and no primary site of disease found on usual evaluation. FDG PET-CT reveals the primary site in up to 30 per cent of patients.

In cancer staging, FDG PET-CT is of particular value in patients with a high risk of widespread disease; in lung cancer, the commonest cancer in the western world, FDG PET-CT prevented futile surgery in up to 21 per cent of patients and influenced treatment plan in 17 per cent of patients with oesophageal cancer. Colorectal cancer patients with disease localised to the liver only or lungs only are usually considered for surgical removal of the disease in lungs and liver. In a comprehensive and objective survey of published data, Dr Strasberg and Dr Dehdashti found FDG PET as the most accurate test for diagnosing spread of disease beyond the liver and altered management in 25 per cent of patients including reduction of futile laparotomies and hepatectomies. A study of 75 patients found that additional cost of including FDG-PET in the diagnostic work-up of patients with potentially resectable colorectal liver metastases was compensated by a reduction in futile laparotomies. Net monetary benefit (NMB) analysis showed savings over a relevant range of willingness to pay for Quality-adjusted life years (QALY).

Accurate diagnosis of residual disease following treatment is important for planning further appropriate management.  The ability of FDG PET-CT to accurately detect residual disease within scar tissue has changed the management of Hodgkin’s and non Hodgkin’s lymphoma. Use of FDG PET-CT in lymphoma has been shown to cost effective and could contribute to savings in public health care programmes.

Early detection of recurrence of cancer offers the best chance of cure. Delay in diagnosis is often due to difficulty in distinguishing between treatment sequelae and recurrent disease. In a survey of 19 published studies designed to evaluate the use of FDG-PET in the detection of recurrent neck cancer, overall sensitivity and specificity for FDG PET 86 per cent and 73 per cent respectively, compared with CT/MR, 56 per cent and 59 per cent respectively.

Blood tests for detecting proteins in the serum secreted by tumours, such as carcino-embryonic Antigen (CEA)  by colon cancer and thyroglobulin by thyroid cancer is routinely used in follow- up as elevation and raising levels of these serum proteins often heralds recurrence of cancer. In cases where usual assessment cannot identify recurrent disease, FDG PET-CT will reveal previously unknown disease.

The increasing popularity of well person health screening programmes in the UK, brings with it rising number of clients with incidental lesions that need investigation. FDG PET-CT provides an accurate and non-invasive way of characterising these lesions. Dr Chang and his colleagues found that FDG PET-CT correctly identified 89 per cent of such lesions in the lungs.

FDG PET-CT improves care of patients and results in more effective use of scarce health resources. Appropriate use of PET-CT reduces investigations including invasive procedures and helps clinicians make the optimal treatment decision. The strongest case can be made for FDG PET-CT as a  cost-effective tool in the initial management of non-small cell lung cancer by contributing to improved care and less exposure to ineffective treatment.  Research should be focused on providing similar confirmatory evidence in other cancers.

We are just at the beginning. A landmark publication by Professor Florian Lordick and colleagues compellingly showed that in oesophageal cancer patients who are treated with chemotherapy prior to surgery, FDG PET-CT scanning at 14 days after the starting chemotherapy predicted whether the patient has active cancer at surgery. Similar promising results have been demonstrated with other cancers. FDG PET-CT potentially allows for early changes in treatment plan by identifying poor response and spares patients from unnecessary treatment which would not be of likely benefit. This is another example of where FDG PET-CT can improve patient care and result in financial savings.

PET-CT is expected to contribute to important advances in radiotherapy treatment. An ever-increasing body of scientific evidence shows that radiotherapy is more accurately targeted and leads to fewer side effects, when FDG PET-CT is included in planning radiotherapy delivery.  Studies confirming that this approach improves patient longevity are awaited. There is ground breaking research on using PET-CT to direct radiotherapy to areas in a tumour most resistant to radiotherapy, including  areas starved of oxygen, hypoxic areas, by using radiotracers selectively metabolised by hypoxic cells such as [18]F-fluoro-MIZO, copper-ATSM and  areas of high cellular turn-over using fluoro-thymidine. PET-CT will also find new applications with the advent of novel radiotherapy techniques including proton therapy and cyber-knife therapy.

PET-CT is being employed to evaluate new cancer drugs. PET-CT is used to select appropriate patients into clinical trials. It potentially allows for early identification of the effectiveness of the drug studied. Labelling drugs with PET radiotracers will enable scientists to confirm that the drug is reaching the places where they are supposed to and in sufficient quantities to be potentially effective. It is easy to see that such applications of PET-CT can lead to a reduction of the duration of clinical trials and the number of unsuccessful clinical trials, and hence reduce unnecessary financial costs.

By way of example, Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates the growth of new blood vessels. In malignant tumours over production of VEGF promotes growth and spread of cancers. New drugs that hinder production and action of VEGF provide promising new avenues for treating cancer. Using VEGF-PET tracer (89)Zr-ranibizumab in a mouse  model of human cancer dynamic changes were demonstrated during sunitinib treatment within the tumour with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation; the first positive step for a possible new anti-cancer drug.

PET-CT in tandem with advances in treatment and refinements in CT and MR will undoubtedly change care of cancer patients beyond its present recognition. In our life times we will see individualised treatment at all stages of the cancer journey in our cancer patients.

Individualised treatment is often viewed from the standpoint of healthcare professionals as I have done in this essay but it important that it should also be considered from the standpoint of the patient and with a broad interpretation. Patients provide us with a yet unutilised powerhouse of energy to improve healthcare. Currently, it is healthcare professionals in the main that shape current and future health care programmes.  Empowering patients so that they are at the driving seat to model developments in health care may lead to as yet unseen and unexpectedly positive effects on our healthcare.

Ground-breaking modern medical discoveries are made not by one individual but by successful collaboration and cross fertilisation of ideas. In an age of increasing specialisation and sub-specialisation, all stakeholders including scientists, engineers, medical professionals, patients and commissioners who fund healthcare need to take every opportunity to meet to exchange ideas and develop a broad understanding of each others disciplines. This is going to be of significant importance in the advancement of areas of medical science and including cancer diagnostic imaging.

Author BIO

Wai Lup Wong is a Clinical Director London PET-CT centre Harley street. He is also a Clinical Guardian (PET-CT) Department of Health UK. Past President Royal Society of Medicine (Radiology). At St Thomas’ hospital, he took the radiological lead in the team that pioneered computer combination of PET to CT in the head and neck and demonstrated the advantage of PET-CT in the assessment of head and neck cancer.  He grew up in Malaysia and continues to spend time in the country of his birth.

Author Bio

Wai Lup Wong