**8. References**


The successful result of the IMPACT trial showing the survival advantage with Sipuleucel-T is expected to lead to a dramatic increase in the use of systemic immunotherapy for prostate cancer (Sonpavde et al., 2011). Presently there are only production facilities within the USA and the cost is likely to remain prohibitive for many healthcare systems. Radiation has great potential to augment the effect of systemic immunotherapy and we can expect many combination trials in the future. Clinical trial design in this setting will remain challenging as immunotherapy appears to improve overall survival but demonstrable tumour or biochemical responses are often delayed. Augmenting immunotherapy with radiation may

PCa has become a huge burden on the health and wealth of Western societies. It is now the commonest solid malignancy and in spite of an excellent general outcome it is expected to become the main cause of cancer-related death in men. There is therefore an urgent need for improved therapies. Sipuleucel-T for PCa was the first immunotherapy to show a survival advantage in cancer, and it has been quickly followed by ipilimumab in melanoma. Radiotherapy has many applications for PCa and it is clear that there are many interactions between immunotherapy and radiation. In general these are positive such that immunotherapy may improve outcomes for those being irradiated and vice versa. The challenge is to move the science into the clinical setting, optimising combinations and

sequences, identification of appropriate biomarkers and designing appropriate trials.

(Cardiff UK) to ZT, LKS and JS and by Velindre NHS Trust R&D (Cardiff, UK) to JS.

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in patients with prostate cancer and are able to lyse prostate tumor cells. *Cancer* 

Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. *J* 

K., Luiten, R., de Ru, A., Neijssen, J., Griekspoor, A., Mesman, E., Verreck, F., Spits, H., Schlom, J., van Veelen, P. & Neefjes, J. (2006). Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor

interleukin-10-induced semi-mature dendritic cells induce anergic CD4(+) and CD8(+) T cells via presentation of the internalized soluble antigen and crosspresentation of the phagocytosed necrotic cellular fragments. *Cell Immunol* 215, 2,

Haustermans, K. & McBride, W. (2008). T-cell responses to survivin in cancer

Drake, C. (2008). Phenotypic analysis of prostate-infiltrating lymphocytes reveals


**10** 

**Bone Seeking Radiopharmaceuticals** 

Prostate cancer is the most common malignancy in men in the Netherlands. The majority of patients with advanced prostate cancer develop skeletal metastases, with bone pain as a frequent symptom. This poses a significant medical problem. Amongst other treatments, bone seeking radiopharmaceuticals are used to palliate painful metastatic bone disease. Efficacy has been sufficiently proven, as well as safety and feasibility. Practical issues as well

This chapter will discuss the treatment of metastatic bone pain in hormone-refractory prostate cancer patients with bone seeking radiopharmaceuticals. Two main issues will be

1. Bone seeking radiopharmaceuticals in clinical practice. Issues regarding radiation safety and a protocol for routine use of bone seeking radiopharmaceuticals will be discussed

But first a short introduction will be given on clinical relevance and bone seeking

The incidence of malignancy in the Netherlands was 74.500 patients in 2005. This will increase to approximately 95.000 new cases in 2015. Because malignancy related death is decreasing and it is likely to decrease further the prevalence of cancer patients will increase to an estimated 692.000 patients in 2015, compared to 366.000 in 2000 (an estimated doubling time of 15 years) (Coebergh, van de Poll-Franse, and Alers 2004; Visser and van Noord 2005). One of the major causes of cancer related death in men is prostate cancer. These

The incidence of prostate cancer is high worldwide. It is the most common malignancy in men in the Netherlands. Approximately 9000 men are being diagnosed with prostate cancer each year (Figure 1). The rising incidence may be attributed to the incremental use of screening methods using prostate specific antigen (PSA) to detect prostate cancer. This hypothesis is supported by the growing number of patients being diagnosed with early

as new developments and future prospects will be discussed.

2. Enhancement of efficacy of bone seeking radiopharmaceuticals.

in order to improve routine clinical care.

**2. Prostate cancer and skeletal metastases** 

radiopharmaceuticals in general.

patients will be the focus of this chapter.

**1. Introduction** 

discussed:

Marnix G.E.H. Lam1 and Bernard A. Zonnenberg1,2

**for Metastatic Bone Pain** 

*1Department of Radiology and Nuclear Medicine* 

*2Department of Internal Medicine University Medical Center Utrecht* 

*The Netherlands* 

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. *Jama* 296, 19, (Nov 15), 2329-2335.

