Cancer Screening

Early diagnosis through screening mammography is the most effective means of decreasing the death rate from breast cancer. While mammography is inexpensive, the interventional procedures that result from detected abnormalities (both false and true positives) increase the cost of this population-based screening program significantly. In fact, breast biopsy actually delivers a benign result in over 80% of cases making it the most costly per capita component of a breast cancer screening program. If a mammogram reports a suspicious finding, then a biopsy is required to decide whether an abnormality is in fact a breast cancer. Our previous research has developed a Bayesian network that calculates the risk of breast cancer based on demographic risk factors and mammography findings. The objective of this research is to optimize the biopsy decisions for breast-cancer patients such that the early diagnosis of invasive breast cancer is improved while unnecessary procedures are minimized. We use Markov decision processes (MDP) to find the optimal probability thresholds for the decision to perform breast biopsy for patients with different age groups. We formulate this problem as a discretetime finite-horizon MDP. We perform a structural analysis of this MDP. Our computational experiments use clinical data, and show that these optimal probability thresholds change with patient age. In particular, our optimal policies suggest that as women get older they should be biopsied less aggressively. We compare our model to clinical practice and find that our model has a potential to improve breast cancer diagnosis significantly. Biographical Sketch Oguzhan Alagoz is currently an Assistant Professor of Industrial and Systems Engineering at the University of Wisconsin-Madison. He received his PhD in Industrial Engineering from the University of Pittsburgh in 2004. His research interests include medical decision making, completely and partially observable Markov decision processes, discrete-event system simulation, scheduling, and stochastic programming. His works have appeared in journals such as Operations Research, Management Science, IIE Transactions, Medical Decision Making, and European Journal of Operational Research. His research is funded by NSF and the National Cancer Institute of NIH. Refreshments will be served in 401 Daniels Hall at 4:00 p.m.

A minor criticism of the book, is that few of the practical protocols quoted seem to have been improved by application in the authors' own laboratory. If one uses a technique regularly, it is usual to come up with little ways of improving the method. In this book, most of the protocols seem to be copied unchanged from the original source. For example, in protocol 3.11 on performing DNA measurements from paraffin-embedded material, the authors suggest the use of 30 ym sections, whilst it has been recognised for some time, that this is not the optimum and that 50 m sections often give significantly better results. Further, many laboratories have automated this technique, to make it quicker and more convenient to perform.
Although I have used Chapter 3 as an example, my impression is that these criticisms apply throughout the book. Undoubtedly, this book contains useful information but the market for flow cytometry books is becoming more competitive. From the middle of 1990 to mid-1992, at least eight flow cytometry books have, or are scheduled to, appear on the market. Thus, any new book needs to have a clear objective and to be well written and organised. In my view, this book tends to fall between stools in its aims, and could have benefited from a better level of organisation. Given the availability of alternative books, I would find it hard to recommend this book to new colleagues or students.
Since the first haemopoietic growth factors became available for clinical testing over 5 years ago, there has been a rapid expansion in the literature. The two editors Roland Mertelsmann and Friedhelm Herrmann of this multi-author text, have made major contributions to this field. They have invited contributors to initially address the biology and basic concepts of haemopoietic growth factors before embarking on clincial applications.
As might be expected with over 75 authors, there is some repetition and the standard of contribution varies. The preclinical chapters give a good review of the cytokines available for testing, their production, mechanism of action, and receptor expression. The book then naturally progresses to the studies in sub-human primates before coming through to man. The clinical data are predominantly from Phase I and II trials of Granulocyte and Granulocyte-Macrophage Colony Stimulating Factors, although data are presented on Erythropoietin and Interleukin-3. This section deals mainly with reduction in the period of neutropenia after chemotherapy or bone marrow transplantation, but there are also chapters on myelodysplasia and aplastic anaemia. There is an interesting section on the effect of colony stimulating factors on malignant cells. This concentrates predominantly on the potentially advantageous use of these agents to recruit myeloid leukaemic cells into cycle prior to chemotherapy. The book concludes with pre-clinical data on Interleukin 4 and 6 which have just entered clinical trials. It may be slightly too early to give firm recommendation for the clinical indication for the use of haemopoietic growth factors, but I felt that an attempt should have been made to have a chapter in which the clinical data presented were critically evaluated. Now that these agents are being marketed, I suspect that clinicians having read the title of this book would have expected more guidance and help on the best way to utilise these powerful agents in the most cost beneficial manner for their patients. With the plethora of talent and experience available from the authors contributing to this book, it should have been possible to entice one of them to have written this finale.
A review at this time can only be a 'snapshot' of this rapidly progressing field. Readers will, however, find that this review will give them an excellent basis of knowledge critically to evaluate publications as they appear. It will appeal predominantly to clinicians wishing to rapidly assimilate the basic science as well as the clinical results. This book is the report of a workshop 'to uptake conclusions on screening for cancer of sites previously considered, and to evaluate some new sites' held in April 1990 and is the fifth monograph arising from the UICC Project on Evaluation of Screening for Cancer. In one volume the 'State of the Art' on screening for cancers of the breast, colorectum, cervix, ovary, prostate, stomach, nasopharynx, and for malignant melanoma and neuroblastoma is brought together. Each cancer is reported in a separate section comprising a number of chapters (44 in all) written by 88 experts. Each section begins with a brief summary of the state of the art on screening for that particular cancer including a list of recommendations for research. This is followed by a number of chapters from different authors' presentations at the workshop and finally an edited summary of the discussion. The book is clearly laid out for reference purposes and presents the concepts of screening straightforwardly. The Editors state, in their Preface, that the book is targeted at those 'interested in screening for cancer including government and non-government organisations concerned with cancer control' and cancer researchers. Experts in cancerscreening may find the book rather too simple but it is pitched at the right level for the non-expert. Those hoping that the book will summarise the results of all the various studies to date will be disappointed; in Chapter 1 on the UK Trial, for example, the discussion is mainly concerned with sensitivity, specificity and biopsy rates.
The first section on breast cancer contains five chapters each on one of the well-known trials of screeningthe UK trial, the trials from Finland, the Swedish 2-County trial, the Malmo trial and that from Canada. Different aspects of these studies are described and some of the puzzling differences in results discussed. A sixth chapter on breast self-examination (BSE) as a strategy for downstaging in developing countries and the importance, and feasibility, of giving adequate treatment without major technological investment is unfortunately too early to give any results of the USSR/Germany/WHO trial. A clearly presented account of the principles involved in different types of cost-effectiveness analysis completes this section.
The section on cervical screening includes chapters on natural history, a description of the screening programmes in the Nordic countries indicating the stark contrast between the success of the best-organised programmes there to the relative lack of success of the programmes in Canada, and indeed in the UK. The importance of 'political will' in ensuring the success of national programmes and the difficulties of reducing the overscreening of low-risk groups are rightly emphasised. Chapter 18 contains an excellent discussion of the evidence for the effect of timing of referral for colposcopy in terms of degree of dysplasia. While the first four chapters in the section consider cervical screening in developing countries where as few as 5% of women may have been screened within the previous 5 years. The enormous problems of setting up and evaluating even the simplest of organised programmes (which have in the past at least, defeated evensome developed countries) are discussed. This surely must be a major challenge for preventative medicine in the next decade.
Sections 1 and 3 thus discuss two cancer sites where there is sufficient evidence of the potential or actual advantages of screening to warrant screening programmes as a matter of public health policy. The remaining sections are devoted to those cancers where screening is a research activity and where to date insufficient evidence has accrued to justify public health policies on screening. Recommendations for the research necessary to reach a decision as to whether a national screening program is cost-effective are given. There are indications that for most cancers there is a long way to go while for others (for example, prostate cancer) there are strong contraindications for large scale screening.
This book is useful reading for all those involved in actual or potential screening programmes, and its references provide well for those who wish to read further. I would particularly recommend it to clinicians interested in screening as the wider public health implications and cost-effectiveness aspects are emphasised throughout.  Ltd, 1991, 193 pp. $59.95. The authors state in their preface that the book is not an all-encompassing textbook, but intended more as an introductory handbook for personnel of nuclear medicine departments. We must agree that they have succeeded in presenting us with one such primer, managing to put together a concise yet detailed text, very rarely sacrificing content for brevity and yet keeping the amount of material in a manageable size of 168 very readable pages. This book fills a gap in existing literature in Nuclear Medicine. The quality of the material is consistent throughout, and the clarity and readability of the text reflects the authors' experience in this field.
The volume is a handsomely edited book. The material is laid out in 8 carefully chosen chapters, the first three addressing preclinical aspects of the use of monoclonal antibodies, one (ch. 5) on the technical considerations of immunoscintigraphy, and four chapters dealing with the clinical application of the technique per se. A useful glossary complements the text.
The first chapter provides a good overview of production/ purification procedures, giving the new initiate a clear overall idea of the techniques and problems associated with the manufacture of monoclonal antibodies. The second chapter describes methods of labelling antibodies for scintigraphic purposes; although improvements in chelator efficiency with the introduction of the macrocyclic chelating agents may be more pertinent in a discussion of radioimmunotherapy, at least a passing comment with some references would have made for a more complete treatment of the subject.
The third chapter is a balanced and un-biased exposition of the role of pre-clinical evaluation of antibodies in animals models. Some elegant work of the authors' is presented, the corollary though being (p. 82) '. . . the true clinical value of an antibody will not be realised until it has been tested in patients.' Chapter four entitled: 'Administration of Antibodies to Patients', despite having to bring together a rather large array of heterogeneous information, ranging from ethico/legal considerations governing the administration of antibodies and protocol design, to pharmacokinetic and biodistribution characteristics of antibodies in patients, manages to negotiate the material in a lucid and informative manner.
Chapter five describes the technical aspects, considerations and variants introduced to routine scintigraphy to accommodate for pecularities of the use of immunoradiopharmaceuticals. It is well balanced and clearly presented. However we feel that a table like 5.4 with the authors' recommendations for routine immunoscintigraphy would have made for a more complete picture.
The next two chapters address the major objective of the book, which is to give a spectrum of the current and possible applications of immunoscintigraphy in clinical practice. The objective is attained remarkably well and it is to the author's credit that overoptimism does not intrude into their critical evaluation of the current clinical applications, problems and efficacy of immunoscintigraphy. The last chapter gives a very good account of possible innovations that may realise the exciting potential of this tool.
In conclusion this is a well-balanced, succinct text which achieves the objectives it sets out to accomplish. We would happily recommend it as useful reading for any physician contemplating postgraduate studies in this field.

A. Maraveyas A.A. Epenetos
Tumours of the Epidermis K. Hashimoto & A.H. Mehregan. Boston: Butterworth Scientific, 1991, 270pp. £45.00. This volume is the third in the practical dermatopathology series and it is stated in the introduction the monograph is based on morphological descriptions of the individual entities described.
After a standard introductory chapter on the biology of human skin, the book is divided into six further chapters on benign epidermal tumours, basal cell epithelioma, actinic keratosis, Bowen's disease, keratoacanthoma and squamous cell carcinomas. Thus the melanocytic lesions, the most important problem for oncologists, are not included in this particular volume. The book is very much aimed at a morphologist and probably at a pathologist. There is little in each section of aetiology or on experimental models of the individual lesions; there are brief descriptions with a few illustrations of the clinical appearances, and thereafter there are many pages of high quality black and white photomicrographs of the morphological, histological appearance of the lesions under discussion. Treatment and management of the lesions is usually consigned to a page at the end of each individual chapter. All chapters are generously referenced.
I think many readers of the British Journal of Cancer would find a book with rather more on current theories about aetiology and current work on the role of for example, the ras family of oncogenes and the P53 gene family in these lesions discussed. Oncogenes are mentioned only very briefly and in passing. Similarly I think many who are interested in the morphological appearance of these lesions might prefer colour photography. There is no doubt in the past few years the more readily availability of colour illustrations in books of this type has made them much more attractive, and in general much more useful. At forty-five pounds the book is modestly priced, but before purchasing, those interested should perhaps consult a larger dermatopathology text such as the excellent one by Phillip McKee, which is profusedly illustrated in colour and consider whether or not the slightly greater expense of the McKee volume could be justified.

R.M. MacKie
Palliative Care for People with Cancer Edited by J. Penson and R. Fisher, London: Edward Arnold, 1991, 293 pp. £14.95. This is an excellent book. The contributors are in touch with the real world and they convey their wide experience in a clear, factual style which all practitioners in this field will find helpful. Although Palliative Care is a vast subject, this book covers its practical, philosophical and spiritual aspects in an admirably comprehensive fashion. It thus deserves a place as an essential reference wherever cancer patients are cared for.