Tx response evaluation in RCC I.R.C.C.S. Policlinico San Matteo, Pavia Issues relative to Tx response evaluation in RCC Dr. Camillo Porta S.C. di Oncologia Medica I.R.C.C.S. Policlinico San Matteo, Pavia

take into account that … We should take into account that … RCC is an extremely peculiar cancer in terms of response evaluation ... ... mainly due to its unique molecular pathogenesis

From biology to the clinic

Peculiarities of targeted agents in terms of MOA ASL MRI H&E stain (2x); CD34 stain (20x) Rini B, Atkins M. Lancet Oncol 2009;10:992-1000

Peculiarities of targeted agents in terms of MOA 10 x 6 cm 11 x 7 cm Abou-Alfa GK, et al. J Clin Oncol 2006;24:4293–300

Peculiarities of targeted agents in terms of MOA Baseline Follow-up 1 Follow-up 2 Volume (cm3) 295 341 285 % necrosis 2.09 53.07 51.03 Abou-Alfa GK, et al. J Clin Oncol 2006;24:4293–300

Peculiarities of targeted agents in terms of MOA Baseline After 4 weeks of sorafenib therapy Gatzemeier U, et al. ASCO 2006, Atlanta, GA, USA

From biology to the clinic

18FDG PET and its limitations in RCC Rioja J, et al. BJU Int 2010;106:1578-93

Easy and cost-effective, but … Color-Doppler CEUS to predict PFS Baseline Week 6 Courtesy of Escudier B (ASCO 2005)

Girentuximab (anti-CAIX MoAb) Other tracers: Girentuximab (anti-CAIX MoAb) Stillebroer AB, et al. Eur Urol 2010;58:75-83 Stillebroer AB, et al. Cancer Imaging 2007;7:179-88

Girentuximab (anti-CAIX MoAb) Other tracers: Girentuximab (anti-CAIX MoAb)

Some lesions are neither measurable nor easily evaluable Therasse P, et al. J Natl Cancer Inst 2000;24:205–16

The future could be … Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Potential: May be used to study microvascular density, vascular permeability, extravascular/extracellular space What we know: Successful therapies result in changes in DCE-MRI contrast-enhancement parameters which may prove to be accurate and early indicators of response One study demonstrated that DCE-MRI may act as a sensitive biomarker for response to the VEGFR inhibitor PTK787/ZK2225841 Pitfalls: High variability of the methods used for data acquisition and analysis lack of a general consensus on how best to acquire and/or analyse data Only consensus recommendations are, at present, available2 1Morgan B, et al. J Clin Oncol 2003;21:3955–64 2Evelhoc J, et al. NCI Cancer Imaging Program (http://imaging.cancer.gov)

The future could be … Magnetic Resonance Spectroscopy (MRS) What it is: An application of MRI that provides chemical information about specific tissue metabolites How it works: Conventional MRI detects the NMR spectra of water in tissues, while MRS detects the resonance spectra of chemical compounds other than water, allowing for a true depiction of in situ chemistry This is distinctive for many pathological conditions, including cancer, and for different metabolic states (eg, necrosis) Pitfalls: Expensive Validated only for brain tumours Lack of standardisation Increased level of choline and a decreased level of N-acetylaspartate, a pattern indicative of recurrent glioma and radiation necrosis

In conclusion … We badly need new response criteria for molecularly targeted agents Also in this field, enrollment of patients into specifically designed studies is crucial

Thank You for Your kind attention!!! c.porta@smatteo.pv.it