636 CLINICAL ONCOLOGY

breast cancer population there is a tendency for bonemetastases to be prominent in the post-menopausaloestrogen receptor-positive subpopulation. Such preferen-tial sites for metastases may be due to the biology of thetumour, host effects or treatment effects. Treatmenteffects due to sanctuary sites are well documented forother tumour types; for example, in childhood leukaemia.Trastuzumab does not cross the bloodebrain barrier due toits large molecular size [3], and a similar sanctuary siteeffect may therefore occur. In addition, the improvedsurvival of HER-2-positive patients treated with trastuzu-mab allows more time for CNS disease to develop. Althoughthis cannot be discounted as a factor, our results insteadsuggest that the high observed incidence of CNS disease inthis population may be an intrinsic property of HER-2 over-expressing tumours, as the proportion of HER-2 over-expression of 57% is more than double the expected rateof the general breast cancer population, usually quoted at20e25% [4,5]. The limitations to this study include HER-2status not being available for all identified patients, andselection bias of patients who were fit enough to benefitfrom whole brain radiotherapy at the time of developingbrain metastases.

As the development of CNS disease may be an intrinsicproperty of HER-2 over-expressing breast cancers, strate-

gies such as prophylactic cranial irradiation could beconsidered, as is already standard practice in other tumourtypes with this biology. Our findings support the trials ofprophylactic cranial irradiation at diagnosis of metastaticdisease in HER-2-positive breast cancer.

C. PATERSONA. MCINTYREP. A. CANNEY

Beatson West of Scotland Cancer Centre,Glasgow G12 0YN, UK

References

1 Bendell JC, Domchek SM, Burstein HJ, et al. CNS metastasis inwomen who receive trastuzumab-based therapy for metastaticbreast cancer. Cancer 2003;97:2972e2977.

2 Cobleigh MA, Vogel CL, Tripathy D, et al. Efficacy and safety ofherceptin as a single agent in 222 women with her2 overexpressionwho relapsed following chemotherapy for metastatic breastcancer. Proc Am Soc Clin Oncol 1998;17:97a (abstract 376).

3 Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol 2000;18:2349e2351.

4 Slamon DJ, Clark GM, Wong WG, et al. Human breast cancer:correlation of relapse and survival with amplification of theher2/neu oncogene. Science 1987;235:177e182.

5 Seshadri R, Firgaira FA, Horsfall DJ, et al. Clinical significance ofher2/neuoncogene amplification in primary breast cancer. J ClinOncol 1993;11:1936e1942.

doi:10.1016/j.clon.2009.05.002

Oral Bisphosphonates, Concurrent Thoracic Radiotherapyand Oesophagitis

Sir d We wish to report the development of severeoesophagitis in a patient after palliative radiotherapy to thethoracic spine, while on oral bisphosphonates.

A 67-year-old woman had a left mastectomy for breastcarcinoma in 1996. Ten years later she developed chest wallrecurrence, which was excised and treated with post-operative radiotherapy without complications.

The patient was re-referred in December 2008 withthoracic spine discomfort. Investigations confirmedextensive bone metastases. Palliative radiotherapy was givenin a single fraction to the thoracic spine from T7 to T10. Asingle posterior megavoltage (6 MV) field was used witha dose of 12.5 Gy prescribed at Dmax (this is a long-establishedstandard palliative regimen in this department [1]).

Oral ibandronate 50 mg once daily was started at thesame time. Serum creatinine was normal. Eighteen dayslater she developed dysphagia, could not tolerate food ororal fluids, and had lost weight. She was admitted forintravenous fluids, opioid analgesia and supplementarysupport. Bisphosphonate treatment was stopped, hersymptoms improved and after 48 h she was dischargedhome.

She was reviewed 3 weeks later. Mild dysphagiapersisted, but she was eating normally and was gainingweight. Her bone pain had improved (no analgesia). Shewas subsequently started on intravenous bisphosphonates.

The authors are aware of a similar clinical experience inanother patient treated with palliative radiotherapy to thethoracic spine while on oral bisphosphonates.

Bisphosphonates have a valuable role in the treatment ofbone metastases in breast cancer. They inhibit osteoclasticresorption of bone, reduce the rate of bone turnover, whichin turn, reduces the rate of skeletal related events [2].Ibandronate is a third-generation, oral aminobisphosphonate.Gastrointestinal toxicity, including oesophagitis, has beenreported with oral bisphosphonates [2,3]. Patients are givenprecise directions as to their administration to minimiseoesophagitis. Caution has been advised in using oral bi-sphosphonates in patients with known oesophageal disease,such as achalasia, stricture, Barrett’s oesophagus, severereflux and scleroderma. Guidelines published in Ontarioadvocate that oral bisphosphonates should be avoidedfor patients with a high likelihood of gastrointestinalupset, and those who are likely to develop nausea,vomiting or oesophagitis from radiotherapy or emetogenicmedication [4].

The concurrent use of palliative radiotherapy for bonemetastases and bisphosphonate treatment is common, butthere are few data on toxicity [5]. Severe adverse eventsand oesophagitis requiring hospital admission do seemuncommon. In lung cancer there is a low and mild level ofoesophagitis after thoracic radiotherapy, where bisphosph-onates are not used [6]. Given our clinical experience, itwould seem prudent to consider avoiding using oralbisphosphonates concurrently with treatment likely tocause oesophagitis. Their use could be deferred until the

637LETTERS

symptoms of oesophagitis due to radiotherapy havepassed.

C. LEEB. MAGEE

Department of Clinical Oncology,Christie Hospital, Manchester M20 4BX, UK

Fig. 1 e Checklist fo

References

1 Easson EC, Pointon RCS, editors. The radiotherapy of malignantdisease. Berlin: Springer; 1985.

2 Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breastcancer. Cochrane Database Syst Rev 2005;3:CD003474.

r writing learning outcomes. Adapted from inform

3 Coleman RE, Purohit OP, Black C, et al. Double-blind, rando-mised, placebo-controlled, dose-finding study of oral ibandro-nate in patients with metastatic bone disease. Ann Oncol 1999;10:311e316.

4 Warr D, Johnston M. Cancer care Ontario practice guidelinereport 2004.

5 Hoskin PJ. Bisphosphonates and radiation therapy for palliationof metastatic bone disease. Cancer Treat Rev 2003;29:321e327.

6 Brock J, Ashley S, Bedford J, et al. Review of hypofractionatedsmall volume radiotherapy for early-stage non-small cell lungcancer. Clin Oncol 2008;20:666e676.

doi:10.1016/j.clon.2009.06.002

Proposed Ethics and Law Component of the ClinicalOncology Curriculum

Sir d I am interested to read the letter and proposal byGuglani and Benstead [1] and would be very much infavour of taking forward its incorporation into thecurriculum.

There are many examples of communication skillscomponents to higher medical training curricula, someof which incorporate ethical and legal issues. Closelyrelated to oncology is palliative medicine, in whichcommunication skills to be obtained are outlined asa subheading under psychosocial care, and ethical issuesto be understood and practiced are listed in their ownparagraph later [2]. There are also many different formatsof medical curricula, not all of which yet seem to fullyembrace the educationalists’ view of learning outcomes.The Postgraduate Medical Education and Training Boardhas set out the requirement to educate our doctors by anoutcome-based approach and competence-based assess-ments. Therefore, learning outcomes need to be writtenin a way in which they can be clearly, fairly andtransparently assessed [3,4]. Bloom’s classification ofcognitive skills suggests different levels of cognitive

functioning associated with acquisition of information,and specifically, related behaviours [5]. There are alsosuggestions for the classification of practical, clinical,interpersonal and transferable skills, as well as attitudinaland affective behaviours. Finally, a checklist for writinglearning outcomes is provided (Fig. 1):

I propose that the key areas that should be covered ina clinical oncology curriculum, are:

1. Informed consent2. Clinical trials and research3. End of life issues4. Confidentiality5. Financial issues

The other two main aspects of ethical and legal concernin oncology are perhaps less relevant to the clinicaloncology curriculum per se (the use of genetics in cancerresearch and care; euthanasia and assisted suicide).Patient autonomy is integral to all of these key ethicaland legal headings [6].

Writing good learning outcomes is not an easy task, andso I have not attempted to do so on this occasion. My mainreason for replying was to offer some of the currentthinking in the medical education literature, and as

ation provided by the British Columbia Institute of Technology.