Radiotherapy for bone metastases and neuropathic bone pain

Abstract

I have a background of active research in Radiation Oncology since passing the final examination of the Royal Australian and New Zealand College of Radiologists ( RANZCR ) at the first attempt in 1992. My first two papers were published the following year [ 1,2 - see curriculum vitae ], and there are currently 49 publications ( 26 first authorships ). My primary research interest has involved the use of radiotherapy ( RT ) for palliation of painful bone metastases. This interest originated from a year at Mt Vernon Hospital, UK, as the inaugural RANZCR Windeyer Fellow in Clinical Oncology ( 1993 ). I worked with Dr Peter Hoskin, a leading figure in the British Bone Pain Trial Working Party responsible for three randomised fractionation trials on this subject. These and many other previous and subsequent studies have demonstrated ( counter - intuitively ) that low dose single fraction RT is as effective as higher dose fractionated schedules in relieving bone pain, with intention - to - treat overall response rates ( RRs ) of about 60 %. However, the studies provided virtually no data on the efficacy of RT specifically for bone pain with a neuropathic component ( NBP ), a scenario occurring in perhaps as many as 20 % of patients with bone metastases during the course of their disease. On returning to Australia as a consultant radiation oncologist at the Royal Adelaide Hospital in 1994, I joined the Trans - Tasman Radiation Oncology Group ( TROG ), the major radiotherapy clinical trials group in Australasia. During the following year, I developed a protocol for a randomised controlled trial comparing one with five fractions of RT for NBP ( TROG 96.05 ). The first patient was registered in February 1996, and a total of 15 centres in Australia ( 11 ), New Zealand ( 3 ) and UK ( 1 ) took part. A National Health and Medical Research Council Project Grant of $ 172,000 was awarded for the study ( 1998-2000 ). Preliminary findings ( blinded to trial arm ) were published in 2000 [ 23 ], and extensive quality assurance activities for the trial were summarised in two further publications [ 21,38 ]. The accrual target was met in December 2002 ( n = 272 ) and the final analysis was reported as an oral presentation at the 12th European Cancer Congress, Copenhagen, September 2003. The essential findings were that NBP responds similarly to localised pain ( overall intention - to - treat RR 57 % ) with no statistically significant difference in RR or time to treatment failure between randomisation arms [ 43 ]. A subsequent cost analysis quantified the relative cost to the Australian healthcare system for the two fractionation schedules [ 47 ]. During the conduct of the trial, I undertook and published a survey confirming the reluctance of Australasian radiation oncologists to use single fractions for painful bone metastases despite the emerging randomised trial results [ 24 ]. I also contributed to the international debate on this controversial subject as co - author with three high profile researchers in a Letter - to - the - Editor [ 20 ], and was a member of an International Consensus Panel on palliative radiotherapy endpoints for future bone metastases trials [ Chow E et al. Radiother Oncol 2002 ; 64 : 275 - 80 ]. I presented invited lectures entitled : Fractionation regimens for metastatic bone pain ( RANZCR Scientific Meeting, Brisbane, 1998 ) ; Neuropathic pain and bone metastases ( Royal College of Radiologists Second Consensus Workshop in Palliative Radiotherapy and Symptom Control, London, 2000 ) [ 27 ] ; Radiotherapy for neuropathic bone pain : TROG 96.05 update ( International Congress of Radiation Oncology, Melbourne, 2001 ) [ 30 ]. My recognised expertise in this field also led to invitations to write an Editorial on the published overviews of bone pain studies [ 40 ], and a book chapter on bone metastases from lung cancer [ 49 ]. My active role in bone pain research continues. The abovementioned International Consensus Panel collaboration led to the development of the first randomised trial on re - treatment of bone metastases with RT. This National Cancer Institute of Canada sponsored international Intergroup trial ( NCIC SC.20 / TROG 03.08 ) has an accrual target of 650 patients and was activated in January 2004. I am the Australasian Co - Chair, securing $ 40,000 funding for local capitation from Cancer Council Australia in February 2004. I believe this body of work constitutes a significant contribution to the literature on RT for bone metastases, and NBP in particular. My research on the latter constitutes the first prospective data ever obtained on RT for this clinical problem, enabling informed selection of single or multiple fraction treatment schedules.