Stavroula Kyriazi¹, David J Collins¹, Robert L Davidson¹, Veronica A Morgan¹, Sharon L Giles¹, Catherine J Simpkin¹, Stan B Kaye², and Nandita M deSouza^1
1Cancer Imaging Centre, Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ²Gynaecological Oncology, Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom

This study investigates ADC histogram-derived parameters as predictive biomarkers of chemotherapy response in forty-five patients with advanced ovarian cancer. Mean ADC, 10^th, 25^th, 50^th, 75^th and 90^th centile points (C10, C25, C50, C75 and C90), and histogram skew were calculated in 126 primary ovarian and metastatic peritoneal, omental and visceral lesions, before and after the 1^st, 3^rd and 6^th cycle of treatment. A linear mixed model was used to analyze differences between responders and non-responders across timepoints . Morphological (RECIST) and biochemical (serum CA125) response were associated with an early and sustained increase of ADC values and decrease of skew (right histogram shift and tendency to normalization). The parameter with the highest discriminant accuracy was percentage C25 change (AUC=.791 and .818 post-1^st and -3^rd cycle respectively).

Junzhong Xu¹, Ke Li¹, Ralph Adam Smith¹, Ping Zhao¹, Mark D Does¹, Henry Charles Manning¹, and John C Gore^1
1Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States

In the current study, both the conventional pulse gradient spin echo (PGSE) and the oscillating gradient spin echo (OGSE) diffusion methods have been implemented to detect the tumor response to chemotherapy by Barasertib (AZD1152) at short diffusion times. The post-treatment ADCs obtained using OGSE at short diffusion times show an opposite change compared with those by PGSE, indicating tumor pathophysiological information at different length scales can be probed at different diffusion times. The results suggest that OGSE provides a different contrast to PGSE methods, and may provide a more specific means to monitor tumor early response to chemotherapy.

Christina Messiou¹, David J Collins¹, Sharon Giles¹, Veronica A Morgan¹, Johann S de Bono², Diletta Bianchini², and Nandita M deSouza^1
1CRUK & EPSRC Cancer Imaging Centre, Institute of Cancer Research & Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ²Medicine, Institute of Cancer Research & Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom

The purpose of this study was to determine whether changes in ADC in patients with metastatic bone disease secondary to carcinoma of the prostate are significantly different in responders compared to progressors following chemotherapy. The results demonstrate that both ADC and ADCslow increase significantly in responders and progressors. No significant change in ADC in stable patients agreed fully with PSA/RECIST criteria of stable disease. The application of thresholds to ADC histogram analysis to identify proportions of normal and diseased marrow may be a better indicator of response or progression and allow wider separation of responding and progressing patients.

Maren Bretschi¹, Maximilian Merz¹, Dorde Komljenovic¹, Woflhard Semmler¹, and Tobias Bäuerle^1
1Medical Physics in Radiology, DKFZ German Cancer Research Center, Heidelberg, Germany

The aim of study was to investigate effects of inhibiting ávâ3/ávâ5 integrins on the vasculature in experimental breast cancer bone metastases using DCE MRI and immunohistological analysis. Results indicated a decrease in blood volume due to smaller and partly nonfunctional blood vessels and an increase in vessel permeability due to the increased number of immature vessels upon integrin inhibition. In conclusion, drug-induced vessel remodeling could be determined by DCE MRI in experimental breast cancer bone metastases.

Chris James Rose^1,2, James P O'Connor^1,2, Alan Jackson^1,2, Yvon Watson^1,2, Fran Maders³, Brandon J Whitcher⁴, Caleb Roberts^1,2, Giovanni A Buonaccorsi^1,2, Gerard Thompson^1,2, Andrew R Clamp^3,5, Gordon C Jayson⁵, and Geoffrey J Parker^1,2
1The University of Manchester Biomedical Imaging Institute, The University of Manchester, Manchester, Greater Manchester, United Kingdom, ²Manchester Academic Health Science Centre, The University of Manchester, Manchester, Greater Manchester, United Kingdom, ³Department of Radiology, Christie Hospital, Manchester, Greater Manchester, United Kingdom, ⁴GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, Imperial College London, London, Greater London, United Kingdom,⁵Cancer Research UK Department of Medical Oncology, Christie Hospital, Manchester, Greater Manchester, United Kingdom

Current and emerging cancer therapies may facilitate dramatic improvements in survival but are expensive and patient response is variable. Being able to identify patients who will benefit could dramatically improve patient outcomes and decrease costs to healthcare providers. We report a retrospective analysis where we model the reduction in volume of CRC liver metastases after treatment with bevacizumab and FOLFOX6 using pre-treatment DCE-MRI-derived biomarkers of microvascular structure and function. Post-treatment tumour volume can be predicted from pre-treatment imaging data with median error of 12%; we interpret our results to explain tumour response in terms of drug penetration and accumulation.

Martin Zweifel¹, Daniel Patterson¹, N. Jane Taylor², J. James Stirling², Ian C Simcock², David J Collins³, James A d'Arcy³, Martin O Leach³, Gordon J Rustin¹, and Anwar R Padhani^2
1Dept of Medical Oncology, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom, ²Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom, ³CRUK-EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey SM2 5PT, United Kingdom

Repeated R₂* measurements were performed during the first 4h after administration of the vascular disrupting agent OXi4503 (combretastatin A1 phosphate, CA1P) in the first in man phase I clinical trial in 22 patients with advanced tumours. DCE-MRI sequences were also performed at 4h. There was a significant dose – K^trans-response relationship. Significant increases in R₂* at 3h and 4h were only seen in the intermediate dose/intermediate K^trans-decrease group. While at intermediate doses, deoxygenated erythrocytes may become entrapped within the tumour vasculature, vascular collapse might result in the emptying of red blood cells and paradoxically not changing the R₂* at higher doses.

Giuseppe Petralia¹, Paul Summers¹, Stefano Viotti², Luke Bonello², Moreno Pasin¹, Maria Giulia Zampino³, Maria Cristina Leonardi⁴, Laura Travaini⁵, Valeria Panebianco⁶, and Massimo Bellomi^1,2
1Radiology, European Institute of Oncology, Milan, Milan, Italy, ²School of Radiology, University of Milan, Milan, Italy, ³Medical Care Unit, Medicine, European Institute of Oncology, Milan, Milan, Italy, ⁴Radiotherapy, European Institute of Oncology, Milan, Milan, Italy, ⁵Nuclear Medicine, European Institute of Oncology, Milan, Milan, Italy,⁶Radiological Sciences, Policlinico Umberto I, University “Sapienza”, Rome, Italy

Better long-term outcome is reported for rectal cancer patients who achieve pathological complete response (pCR) after neoadjuvant chemoradiation therapy (NACRT). Minimalist approaches are a reasonable alternative to radical surgery in such patients, with equivalent outcomes. Conventional T2-weighted MRI is not predictive of pCR, whilst DCE-MRI has shown potential for predicting therapy outcome. 34 patients underwent DCE-MRI before and after NACRT. No pre-treatment DCE-MRI parameter predicted pCR. Ktrans and IAUC60 values after NACRT were lower in pCR group than in patients with residual disease, but the distribution of values does not allow prediction of patients suitable for minimalist approaches after NACRT.

Dingxin Wang^1,2, Ron Gaba³, Brian Jin⁴, Ahsun Riaz⁴, Robert Lewandowski⁴, Robert Ryu⁴, Kent Sato⁴, Ann Ragin⁴, Laura Kulik⁵, Mary Mulcahy^6,7, Riad Salem^4,7, Andrew Larson^4,7, and Reed Omary^4,7
1Siemens Medical Solutions USA, Inc., Minneapolis, Minnesota, United States, ²Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, United States, ³Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States, ⁴Department of Radiology, Northwestern University, Chicago, Illinois, United States, ⁵Department of Hepatology, Northwestern University, Chicago, Illinois, United States, ⁶Department of Medicine, Northwestern University, Chicago, Illinois, United States, ⁷Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, United States

In this study, we tested the hypothesis that Transcatheter Intraarterial Perfusion (TRIP)-MRI monitored intra-procedural changes in tumor perfusion during transcatheter arterial chemoembolization (TACE) may predict future tumor response. Our results demonstrated that intermediate level of tumor perfusion reduction was associated with improved tumor response, and TRIP-MRI measured intro-procedural tumor perfusion reduction and Child-Pugh class were independent factors associated significantly with tumor response. TRIP-MRI, performed within an integrated MR-IR suite, may potentially serve as an objective predictor of future tumor response at the time of TACE procedure.

Sonia P Li¹, N. Jane Taylor², Shaveta Mehta³, Nicholas P Hughes⁴, J. James Stirling², Ian C Simcock², David J Collins⁵, James A d'Arcy⁵, Martin O Leach⁵, Adrian L Harris³, Andreas Makris¹, and Anwar R Padhani^2
1Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom, ²Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, United Kingdom, ³University Department of Medical Oncology, Churchill Hospital, Oxford OX3 7LJ, United Kingdom, ⁴Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305-5427, United States, ⁵CRUK-EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey SM2 5PT, United Kingdom

Bevacizumab is an anti-VEGF antibody targeting abnormal tumour neovasculature. Intrinsic susceptibility-weighted and Diffusion-weighted MRI can depict treatment induced changes in tumour oxygenation and cellularity. 17 patients with chemotherapy naïve primary breast cancer were imaged before and after one single dose of Bevacizumab prior to neoadjuvant chemotherapy. Reductions observed in ADC and DCE-MRI kinetic parameters are consistent with reductions in tumour perfusion. Increases in R₂* are also a result of decreases in tumour perfusion which lead to tumour hypoxia. DCE, DW and ISW-MRI changes after one dose of bevacizumab can serve as early biomarkers of anti-angiogenic action in primary breast cancers.

Dennis Klomp¹, Wybe van der Kemp¹, Mies Korteweg¹, Jannie Wijnen¹, Maurice van de Bosch¹, and Peter Luijten^1
1University Medical Center Utrecht, Utrecht, Netherlands

First the feasibility of detecting phospholipid metabolites in vivo in the human breast is demonstrated using ³¹P MRSI at 7T. Secondly, substantially higher levels of PE and GPE compared to PC and GPC in breast cancer tissue are shown, which may be the cause of increased signal increase at 3.2 ppm in the proton spectrum rather than total choline. Finally, alterations in phopholipid metabolism during neoadjuvant chemotherapy are observed that could not be detected with ¹H MRS. Therefore, ³¹P MRS at 7T seems a promising technique for monitoring breast cancer treatments with potentially a higher sensitivity than ¹H MRS.