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The Institute of Cancer Research (ICR) has made seminal contributions to the development and dissemination of conformal radiotherapy and intensity modulated radiotherapy (IMRT), leading to changes in clinical practice, reduced treatment complications and improved cure rates. ICR researchers developed conformal radiotherapy, which allowed better shaping of the high-dose radiation volume around a tumour, and they then refined this technique to create IMRT, which makes possible the definition of a high dose volume with a concave border allowing further sparing of critical normal tissue. IMRT is now the approved treatment regime for many cancers such as prostate, breast and head and neck in the USA, the UK and many European countries.
Research from UCL Division of Surgery has transformed the breast cancer treatment paradigm so women can complete their local treatment intraoperatively (~30 min), with reduced toxicity. Our work has challenged the dogma of giving several weeks of whole breast radiotherapy (EBRT) after lumpectomy for breast cancer with our idea of irradiating only the tumour bed in selected cases; we have developed and evaluated new technology called TARGeted Intraoperative radioTherapy (TARGIT) within the novel approach of risk-adapted radiotherapy. To date, TARGIT has saved 180,000 hospital visits and could save £60M(UK)/ $280M(USA)/year.
The Institute of Cancer Research (ICR) conducted pioneering translational research into the use of aromatase inhibitors (AIs) in breast cancer. Novel assays were developed that enabled the effects of AIs to be measured accurately and facilitated their rapid entry into large scale clinical trials and subsequent widespread availability. The ICR showed how AIs should be used clinically and helped to establish international guidelines; in some indications AIs are now the accepted standard of care. Research at the ICR has also led to the evaluation and development of novel predictive tests to determine the prognosis of patients on these drugs.
The HiLo trial has changed management for patients with well-differentiated thyroid cancer. Patients undergoing radioiodine ablation therapy are now given a low dose of radioactive iodine, which has fewer side effects, compared to the previous (standard) high dose. Also, to prepare patients for ablation they now have recombinant human TSH (thyrotropin alfa), which is associated with a better quality of life before and during ablation. The combination of low dose radioiodine and thyrotropin alfa means that patients can be treated as outpatients rather than inpatients. This is a more convenient treatment package, reducing health service and societal costs.
Locally advanced prostate cancer (where a tumour has extended outside the prostate gland to surrounding tissues) will affect around 20,000 men per year in the US, and 4,000 men per year in the UK. Prior to the underpinning research, there was no consensus on the standard of care, with hormone therapy often being given alone. The International randomised clinical trial, led by Cardiff researchers showed that treating locally advanced disease with a combination of radiotherapy and hormone therapy halved the risks of dying of prostate cancer. Consequently, it is now a standard of care, enshrined in European and North American guidelines, that all such patients who are fit enough to receive it, should now be offered combined modality radiotherapy plus hormone therapy.
The primary treatment for ductal carcinoma in situ (DCIS, cancer confined to the milk ducts of the breast) is surgery, and breast-conserving surgery is increasingly preferred over mastectomy. The UK/ANZ DCIS trial, co-led by Queen Mary researchers, showed that following surgery, women with DCIS are significantly less likely to develop invasive disease if given radiotherapy, and that this protection persists long term. NICE recommends that, following adequate breast conserving surgery, adjuvant radiotherapy should be offered to patients with DCIS. This recommendation is also current in the United States, Canada, Australia, and many European countries. Based on current figures, we estimate that in UK alone, around 260 women each year are spared a recurrence of breast cancer as a result of this research.
Muscle invasive bladder cancer is the sixth most common cancer and remains a major cause of death and suffering worldwide. The standard treatment for advanced bladder cancer has been surgical removal of the bladder (cystectomy) which is associated with considerable morbidity. Many (20%) patients are elderly, with significant co-morbidities and hence are high risk for a major operation. In the past patients who were not able to undergo surgery were offered palliative radiotherapy. Research at the University of Birmingham has shown that the addition of low toxicity chemotherapy to radiotherapy is as effective as cystectomy in controlling disease progression and has minimal impact on bladder function. This new approach is an excellent alternative to cystectomy and has been adopted as a new standard of care thus demonstrating considerable impact on clinical practice and patient outcome.
Approximately 80% of all breast cancer is hormone receptor positive localised cancer in postmenopausal women. For 30 years the universal standard adjuvant endocrine treatment for these women was five years of tamoxifen, but side effects and recurrences limited its usefulness. Results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial led to a major worldwide change in the standard recommended treatment, from tamoxifen to anastrozole (an aromatase inhibitor). From 2009 this treatment became UK national policy (recommended by NICE), and guidance in other countries (eg Australia, USA) has also been revised. Anastrozole is now routinely offered to women with hormone receptor positive breast cancer in UK and (extrapolating from trial data) we estimate over a thousand are spared a recurrence in UK annually.
Impact: Health and welfare; additional effective therapy for women with advanced, HER2+ breast cancer.
Significance: Allows approximately 10,000 patients a year, whose disease is no longer being controlled by trastuzumab, to receive a more effective therapy than chemotherapy with capecitabine alone.
Beneficiaries: Patients with incurable metastatic HER2+ subtype breast cancer; policy-makers; commerce.
Attribution: Cameron (UoE) was joint chief-investigator on the global pivotal registration trial that led to the marketing authorisation of the drug lapatinib in combination with capecitabine.
Reach: World-wide: the drug is approved in >100 countries and generated >£650M in sales for manufacturer GlaxoSmithKline.
Before 2010, there was no accepted standard treatment for patients with advanced biliary tract cancer. The ABC02 trial showed that the combination of two drugs (gemcitabine and cisplatin) significantly improves survival, with acceptable side effects. Consequently, national and international guidelines have been revised to recommend this regimen as a standard of care. Furthermore, in ongoing trials of novel therapies, gemcitabine/cisplatin has become the comparator group, and the aim is to improve survival above what this can already achieve.