1 / 29

Imaging evaluation of clinical benefit in sarcomas: Dynamic MRI

Imaging evaluation of clinical benefit in sarcomas: Dynamic MRI. Dr Anwar Padhani anwar.padhani@paulstrickland-scannercentre.co.uk Mount Vernon Cancer Centre London. Montreal November 2004. Mount Vernon Cancer Centre & Gray Cancer Institute. Royal Marsden Hospital &

anaya
Download Presentation

Imaging evaluation of clinical benefit in sarcomas: Dynamic MRI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Imaging evaluation of clinical benefit in sarcomas: Dynamic MRI Dr Anwar Padhani anwar.padhani@paulstrickland-scannercentre.co.uk Mount Vernon Cancer Centre London Montreal November 2004

  2. Mount Vernon Cancer Centre & Gray Cancer Institute Royal Marsden Hospital & Institute of Cancer Research Jane Taylor, James Stirling Gordon Rustin, Sue Galbraith, Kate Lankester, Andreas Makris, Mei-Lin Ah-See Ross Maxwell, Gill Tozer Janet Husband and Martin Leach, David Collins, James d’Arcy, Simon Walker-Samuel, Carmel Hayes, Geoff Parker, John Suckling, Ian Judson I acknowledge other contributors who have provided additional materials of their work in support of this lecture Dr H Choi, MD Andersen Cancer Cemtre, Houston Dr WE Reddick, St Jude Children Research Hospital, Memphis

  3. Talk outline • Dynamic MRI – biological basis & quantification • Illustrate utility of dynamic MRI to assess benefit of therapy in patients with bone sarcomas • Predict response to neoadjuvant chemotherapy • Assess activity of residual disease • Biomarker for assessing effects of treatment with antiangiogenesis/vascular targeting drugs • Biomedical challenges in clinical implementation specific to patients with sarcomas Perfusion MR imaging of extracranial tumor angiogenesis. A Dzik-Jurasz, AR Padhani. Top Magn Reson Imaging. 2004;15(1):41-57.

  4. Talk outline • Dynamic MRI – biological basis & quantification • Illustrate utility of dynamic MRI to assess benefit of therapy in patients with bone sarcomas • Predict response to neoadjuvant chemotherapy • Assess activity of residual disease • Biomarker for assessing effects of treatment with antiangiogenesis/vascular targeting drugs • Biomedical challenges in clinical implementation specific to patients with sarcomas Perfusion MR imaging of extracranial tumor angiogenesis. A Dzik-Jurasz, AR Padhani. Top Magn Reson Imaging. 2004;15(1):41-57.

  5. Dynamic contrast enhanced MRI (DCE-MRI) • Technique where enhancement of a tissue or organ is continuously monitored using MRI after bolus IV contrast medium • Low molecular weight contrast media (<1 kDa) • Diffuse into extravascular-extracellular space (does not cross cell membranes) • Experiment lasts a few minutes 7 minutes Haemangiopericytoma Data courtesy of David Collins and Ian Judson, Institute of cancer Research, London

  6. Basis of dynamic contrast enhanced MRI

  7. T2*W DCE-MRI of Mixed Mullerian Tumour Typical acquisition 1-2 mins

  8. T1W DCE-MRI of Mixed Mullerian Tumour Typical acquisition 5-8 mins

  9. T2*W versus T1W DCE-MRI

  10. Evaluation of signal enhancement during DCE-MRI • Qualitative - shape of signal intensity (SI) data curve • Semi-quantitative - indices that describe one or more parts of SI or [Gd] curves • Upslope gradient, max amplitude, washout rate or area under curve at a fixed time point • True quantitative - indices from contrast medium concentration changes using pharmacokinetic modelling

  11. kep(min-1) = 0.5 kep(min-1) = 8.9 kep(min-1) = 3.4 Patterns of enhancement on T1W DCE-MRI and histological correlates Type I (semi-necrotic with reactive changes) Type II (viable tumour) Type III (rapidly proliferating tumour edge) (Taylor and Reddick, Adv Drug Del Rev, 2000)

  12. Pharmacokinetic modelling of T1W DCE-MRI data • Transfer constant (Ktrans) • Extracellular leakage space (ve) • Rate constant (kep) Not today Modified from Tofts 1995

  13. Quantitative analysis with pharmacokinetic modelling • Advantages • Whole curve shape is analysed • Biologically relevant physiological parameters • Independent of scanner strength, manufacturer and imaging routines • Enables valid comparisons of serial measurements and data exchange between different imaging centres • Disadvantages • Data acquisition and analysis is more complex • Lack of commercial software for analysis • Models may not fit the data observed

  14. Clinical indications for DCE-MRI in patients with musculoskeletal lesions • To improve characterisation of lesions* • Monitoring response to treatment • Conventional treatments (chemotherapy/physical treatments) • Novel biological treatments including antiangiogenic/vascular targeting drugs • Assess activity of residual disease after definitive treatment *Ma LD, et al. Radiology 1997; 202(3):739-44 *van der Woude HJ et al. Radiology 1998; 208(3):821-8 *Verstraete KL, Radiology. 1994; 192(3):835-43

  15. Importance of predicting early tumour response to chemotherapy • If pathological response can be reliably predicted after a few cycles of neoadjuvant chemotherapy • Treatment regimen could be adjusted (early surgery, cryotherapy, isolated limb perfusion etc) • Pathological response rates may be improved • Changing treatment could increase expense and exposes patients to greater toxicity There is very little objective data that DCE-MRI can predict responses early after stating neoadjuvant chemotherapy

  16. Good response to treatment (99% necrosis) Baseline 2 months on treatment SUV 13.0 FDG-PET scans Pre-operative SUV 2.4 2 A Courtesy of Dr H Choi, MD Andersen Cancer Center, Houston

  17. Correlation of DCE-MRI and necrotic fraction after chemotherapy Dyke JP, et al. Radiology 2003; 228:271-278

  18. Tumors < 56 cm2 100 kep < 1.167 min-1 80 kep 1.167 min-1 Disease-free Survival (%) 60 40 20 0 1 2 3 5 6 4 0 Tumors > 56 cm2 100 80 kep < 1.167 min-1 60 kep> 1.167 min-1 40 Disease-free Survival (%) P = 0.05 20 0 0 1 2 3 5 6 4 Year Prognostic value of DCE-MRI in osteosarcomas Change in kep as a function of pre-treatment value. Higher permeability at presentation results in greater decreases with therapy 2 ) -1 0 During Therapy (min -2 -4 ep k -6 0 1 2 3 4 5 6 7 k at Presentation (min-1) ep Disease free survival for 31 patients stratified by tumour size and DCE-MRI after 9 weeks of Rx; Reddick WE, et al. Cancer 2001; 91:2230-2237

  19. Tumors < 56 cm2 100 kep < 1.167 min-1 80 kep 1.167 min-1 Disease-free Survival (%) 60 40 20 0 1 2 3 5 6 4 0 Tumors > 56 cm2 100 80 kep < 1.167 min-1 60 kep> 1.167 min-1 40 Disease-free Survival (%) P = 0.05 20 0 0 1 2 3 5 6 4 Year Prognostic value of DCE-MRI in osteosarcomas Change in kep as a function of pre-treatment value. Higher permeability at presentation results in greater decreases with therapy 2 ) -1 0 During Therapy (min -2 -4 ep k -6 0 1 2 3 4 5 6 7 k at Presentation (min-1) ep Disease free survival for 31 patients stratified by tumour size and DCE-MRI after 9 weeks of Rx; Reddick WE, et al. Cancer 2001; 91:2230-2237

  20. Poor access to contrast before treatment Baseline SUV 5.9 FDG-PET scans Poor response to treatment (75% necrosis) SUV 8.3 Pre-operative Courtesy of Dr H Choi, MD Andersen Cancer Center, Houston

  21. Drugs targeting tumour neovasculature Vascular targeting drugs •  Permeability •  rBV • or  rBF Probably depends on drug duration and dose Anti-VEGF drugs  Permeability  rBV rBF

  22. Time course of Combretastatin effects on microvasculature 2 hours post CA4P PreRx Window chamber view P22 Carcinosarcoma IAP - radiolabelled iodoantipyrine B Vojnovic and G Tozer, Gray Cancer Institute

  23. Morphological & kinetic changes After 1st dose of CA4P (52mg/m2) 24 hrs Pre 4 hrs Post

  24. DLT 114 mg/m2 Biologically active dose 52 mg/m2 MTD 88 mg/m2 Galbraith SM, et al. J Clin Oncol – 2003;21:2831-42.

  25. Galbraith SM, et al. J Clin Oncol – 2003;21:2831-42

  26. Phase I goals and DCE-MRI achievements in the CA4P study Galbraith SM, et al. J Clin Oncol – 2003;21:2831-42

  27. 160 • 25 patients with metastatic colon cancer evaluated at baseline, on day 2 and 28 140 120 100 80 Ki (% Baseline) 60 40 20 0 50 300 500 750 1000 1200 Dose (mg) Dose response in Ki for PTK787/ZK in colorectal cancer on Day 2 SEM bars, all colorectal liver metastases No maximum tolerated dose was reached Figure courtesy of A Thomas, B Morgan, Leicester Royal Infirmary Morgan, B., et al., J Clin Oncol, 2003. 21(21): p. 3955-3964.

  28. Phase I goals and DCE-MRI achievements in the PTK787/ZK study Morgan, B., et al., J Clin Oncol, 2003. 21(21): p. 3955-3964.

  29. Conclusions • Dynamic MRI provides unique information on the vascular characteristics of tumours • DCE-MRI can predict extent of histological response to chemotherapy in patients with osteosarcomas/Ewing tumours • Intriguingly, DCE-MRI may inform on drug access (? predict responsiveness) and patient prognosis • Acts as a biomarker that provides pharmacodynamic (PD) information in early trials of antivascular drug and should be used for evaluating combination therapies in sarcomas Dynamic MR imaging of tumor perfusion: approaches and biomedical challenges. DJ Collins, AR Padhani. IEEE Engineering in Medicine and Biology Magazine 2004

More Related