P. Mulvenna

Trial design on prophylaxis and treatment of brain metastases: Lessons learned from the EORTC Brain Metastases Strategic Meeting 2012

Brain metastases (BM) occur in a significant proportion of cancer patients and are associated with considerable morbidity and poor prognosis. The trial design in BM patients is particularly challenging, as many disease and patient variables, statistical issues, and the selection of appropriate end-points have to be taken into account. During a meeting organised on behalf of the European Organisation for Research and Treatment of Cancer (EORTC), methodological aspects of trial design in BM were discussed. This paper summarises the issues and potential trial strategies discussed during this meeting and may provide some guidance for the design of trials in BM patients.

Response to “Diagnosis-Specific Prognostic Factors, Indexes, and Treatment Outcomes for Patients With Newly Diagnosed Brain Metastases: A Multi-Institutional Analysis of 4,259 Patients.” (Int J Radiat Oncol Biol Phys 2010:77:655–661)

To the Editor:We appreciate the interest of Drs. Song, Levitt, and Park in our original publication (1) and in our subsequent response to the letter of Drs. Meyer and Timmerman (2). In their letter, Drs. Song, Levitt, and Park make two main points: Tumors can become more hypoxic after repeated doses of irradiation because of vascular damage (especially with high doses/fraction), and a hypoxic cytotoxin might be preferable to a hypoxic radiosensitizer to combine with stereotactic ablative radiotherapy (SBRT). We agree with the first of these. In fact we have recently shown that irradiated tumor xenografts in mice gradually lose their vasculature after irradiation and become more hypoxic within 2 weeks of radiation (3). As to the second point, we suggested the use of a radiosensitizer such as etanidazole because of clinical experience with the large doses of this drug that could be given with SBRT and the known efficacy of such doses. However, there is no reason why a hypoxic cytotoxin (such as tirapazamine or PR-104) could not be given instead of the sensitizer with SBRT, but because there is less clinical experience with a few large doses of these drugs, we did not suggest this possibility. However the argument that a hypoxic cytotoxin would be inherently superior to a hypoxic sensitizer because of increasing tumor hypoxia is incorrect: there are no data showing that a hypoxic cytotoxin enhances the radiation response of very hypoxic tumors to a greater extent than does a hypoxic radiosensitizer. The possibility of using a hypoxic cytotoxin after the completion of radiotherapy as Drs. Song, Levitt, and Park might be suggesting is a different point and would be akin to delivering adjuvant chemotherapy. This could in theory add to the efficacy of SBRT with a sensitizer.

Releasing interim results from a randomised clinical trial: an example from the QUARTZ trial

QUARTZ is the first phase III randomised clinical trial of whole brain radiotherapy (WBRT) for patients with inoperable brain metastases from non-small cell lung cancer. It is designed as a non-inferiority trial to assess whether WBRT may be omitted without detriment to the patient’s survival while improving quality of life. QUARTZ opened to recruitment in March 2007 and currently has 76 UK and Australian centres open. Despite universal support of the importance of the question and a number of major initiatives aimed at improving recruitment, by mid-2010 recruitment was slower than targeted and the trial was under threat of closure. It was suggested that one of the reasons for investigators not offering the trial to large numbers of their patients and for patients rejecting randomisation, was the lack of good quality preliminary randomised data to support the trial question. Therefore it was proposed to make the unusual step to release interim results from the trial in order to provide investigators with further information upon which to base trial decisions and discussions.

111 Quality of life after treatment for brain metastases: interim data from the MRC QUARTZ clinical trial. Part two, symptoms, quality of life and data completion

111 Quality of life after treatment for brain metastases: interim data from the MRC QUARTZ clinical trial. Part two, symptoms, quality of life and data completion P. Mulvenna1, R. Barton2, C. Faivre-Finn3, P. Wilson4, R. Langley5, C. Pugh5, M. Nankivell5. 1Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom, 2Castle Hill Hospital, Hull, United Kingdom, 3The Christie, Manchester, United Kingdom, 4University Hospitals Bristol, Bristol, United Kingdom, 5MRC Clinical Trials Unit, London, United Kingdom

Quality of life after radiotherapy and steroids in patients with inoperable brain metastases from non-small cell lung cancer: the QUARTZ trial

Mesothelioma Framework, launched by the Department of Health Lung Cancer and Mesothelioma Advisory Group (LCMAG) in February 2007, aims to provide Strategic Health Authorities (SHA’s), Cancer Networks, Primary Care Trusts (PCT’s) and NHS Trusts advice and guidance on how to better organise mesothelioma services in order to standardise and improve the quality of care throughout the UK. The M-NAT initiative will provide an opportunity for nursing services for people with mesothelioma to be developed to a uniformly high level across the country. To date M-NAT has 43 members representing Scotland, Wales and every English cancer network except one. This core membership is able to cascade information and support to the wider community of nurses working within their network. M-NAT has met three times and two more dates are scheduled for 2009. Regular contact with, and support of, the membership is maintained by e-mail communication. The team has undertaken a detailed review of the Mesothelioma Framework and set its initial priorities: • To develop as a national team • To develop a national mesothelioma patient information pack • To develop a national nursing care pathway for patients • To develop a programme of nursing audit and research in mesothelioma. A baseline survey of members has also been undertaken identifying members’ characteristics, level of understanding, knowledge, skills and confidence in meeting the needs of mesothelioma patients and their carers, as well as their expectations and hopes for M-NAT. This poster will describe the M-NAT initiative in greater detail.