|Metabolic & Functional Assessment of Cancer: Clinical Studies|
An International, Multi-Institutional Trial of DCE-MRI
in Children Treated for Osteosarcoma
Wilburn E. Reddick1, John O. Glass1, Catherine A. Billups1, Fred A. Hoffer1, Jesse J. Jenkins1, Juan Quintana2, Milena Villarroel2, Lori Luchtman-Jones3, Najat C. Daw1
1St. Jude Children's Research Hospital, Memphis, Tennessee, USA; 2Luis Calvo Mackenna Hospital, Santiago, Chile; 3Washington University Medical School, St. Louis, Missouri, USA
The current study prospectively evaluated the use of a two-compartment pharmacokinetic model of DCE-MRI to non-invasively evaluate tumor response to neoadjuvant chemotherapy in children treated on a single phase II trial at three institutions (2 US and 1 Chile). DCE-MRI was performed at baseline, week 9, and week 12 of preoperative chemotherapy prior to definitive surgery. Histological assessment of tumor response was determined from en bloc resections. Decreased Ktrans and ve at week 9 relative to presentation was significantly associated with good histologic response to preoperative chemotherapy. Patients with higher Ktrans and ve at presentation were more likely to have good histological response. DCE-MRI is a non-invasive method that can be feasibly used to assess tumor response to neoadjuvant chemotherapy in OS even between institutions in an international setting.
Dynamic Contrast Enhanced MRI as a Predictor of Long
Term Outcome in Pediatric Bone Tumors
Jason A. Koutcher1, Ya Wang1, Howard T. Thaler1, Paul Meyers1, Leonard H. Wexler1, Jonathan P. Dyke2, David M. Panicek1, Lawrence H. Schwartz1, Maayan E. Korenblit1, Wei Huang1
1Memorial Sloan Kettering Cancer Center, New York, New York, USA; 2Weill-Cornell Medical College, New York, New York, USA
Bone sarcomas are among the most common pediatric tumors. The most useful prognostic marker has been percent necrosis at time of surgery post chemotherapy – patients with > 90% necrosis have a better prognosis. Using DCE-MRI, we have found the combination of measuring ve (interstitial volume fraction) and pathological necrosis is a highly significant predictor of long term survival in a group of 25 patients followed for up to 9 years (p<0.002) and is superior to percent necrosis alone which has only borderline statistical significance. Only one of the 25 patients was misclassified by this method.
Treatment Response Predictor Using 31P
MRS for CHOP and R-CHOP Therapy in Diffuse Large B-Cell Lymphoma
Fernando Arias-Mendoza1, Geoffrey S. Payne2, Kristen Zakian3, Marion Stubbs4, Jaime G. Cruz-Lobo1, A J. Schwarz2, Amita Dave3, Franklyn Howe5, N R. Maisey2, D Cunningham2, H Poptani6, M R. Smith7, O A. O'Connor1, R Pettengell5, M O. Leach2, J A. Koutcher3, J R. Griffiths4, A Heerschap Heerschap8, J D. Glickson6
1Columbia University, New York, New York, USA; 2Royal Marsden Hospital, London, UK; 3Memorial Sloan Kettering Cancer Center, New York, New York, USA; 4Cambridge University, Cambridge, UK; 5St. George's Hospital, London, UK; 6University of Pennsylvania, Philadelphia, Pennsylvania, USA; 7Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; 8Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
Our ongoing international multi-institutional research program has demonstrated that the sum of the integrated 31P-MR resonances of phosphoethanolamine plus phosphocholine [Etn-P + Cho-P] normalized by the total nucleotide triphosphates (NTP) acquired prior to treatment initialization can predict treatment failure and drug-free survival in various forms of lymphomas. To make our results diagnosis- and treatment- specific, patients with diffuse large B-cell lymphomas (DLBCL) that were treated with CHOP or R-CHOP were studied. As in our previous reports, we show here that the pre-treatment [Etn-P + Cho-P]/NTP ratio predicts long-term failure to treatment and drug-free survival in these set of patients.
|Prediction of Response to Chemo/radiation Therapy of
Squamous Cell Carcinomas of the Head and Neck by 1H MRS Studies of
Sungheon Kim1, Sanjeev Chawla1, Laurie A. Loevner1, Harry Quon1, Eric J. Sherman1, Gregory S. Weinstein1, Harish Poptani1
1University of Pennsylvania, Philadelphia, USA
In this study 1H MRS was performed in the metastatic cervical lymph nodes of squamous cell carcinomas of the head and neck (HNSCC) to assess the potential of choline as a biomarker for treatment response. Single-voxel 1H MR spectroscopy was performed in 32 patients who were treatment naïve. A negative correlation was observed between tCho and residual tumor volume at the end of treatment suggesting that higher pre-treatment tCho values indicate better treatment response. These studies indicate that pre-treatment choline levels can be used as a marker for prediction of treatment response in HNSCC.
Predicting Final Pathological Response to Neoadjuvant
Chemotherapy in Breast Cancer Using Quantitative MR Spectroscopy Using
Internal Reference Method at 1.5T
Hyeon-Man Baek1, Jeon-Hor Chen, 2, Shadfar Bahri, Rita S. Mehta, Orhan Nalcioglu, Min-Ying Su
1 University of California-Irvine, Irvine, California , USA; 2China Medical University Hospital, Taichung 404, Taiwan
The changes of choline and tumor size in 35 patients receiving neoadjuvant chemotherapy were analyzed. Depending on the final pathological findings, patients were separated into pathologic complete response (pCR) vs. residual disease (non-pCR) groups. In F/U-1 after 2cycles AC, the median change of Cho and tumor size was -62% and -17%, respectively in the pCR group, and was -36% and -15% in the non-pCR group. In F/U-2, all pCR patients had non-detectable Cho. The changes of Cho were greater than the size changes, and higher in pCR than in non-pCR group. Therefore, its role for response prediction warrants further investigation.
Variation of Breast Vascular Maps at Dynamic
Contrast-Enhanced MR Imaging Before and After Neoadjuvant Chemotherapy
of Locally Advanced Breast Cancer
Laura Martincich1, Ilaria Bertotto1, Alfonso Fausto2, Filippo Montemurro1, Daniele Regge1, Francesco Sardanelli2, 3
1Institute for Cancer Research and Treatment, Candiolo, Italy; 2Policlinico S.Donato, S. Donato Milanese, Italy; 3University of Milan, Milan, Italy
In vivo effects of NCT on tumor vascularity are not exhaustively studied by MRI. The evaluation of breast vascularity by DCE-MRI may have a role in the evaluation of tumor response, identifying patients who better benefit from therapy.
Dynamic Contrast Enhanced MRI of Solid
Tumors and Healthy Tissue During Treatment with NGR-TNF, a Novel
Vascular Targeting Agent
Hanneke W.M. van Laarhoven1, Jacques A. van Asten1, Ingrid Desar1, Gian Paolo Rizzardi2, Claudio Bordignon2, Cornelis Punt1, Carla van Herpen1, Arend Heerschap1
1Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Molmed, Milan, Italy
Targeted delivery to the tumor of picogram doses of TNF-alpha can be achieved by coupling TNF-alpha with CNGRC (NGR-TNF), a peptide that specifically targets tumor neovasculature. The aim of this study was to asses the effect of NGR-TNF on solid tumors and healthy liver tissue with dynamic contrast enhanced MRI (DCE-MRI) during a phase I trial with NGR-TNF. Two hours after treatment we observed a significant decrease in kep and Ktrans in solid tumors compared to baseline, but not in healthy liver tissue. This suggests a tumor-specific anti-vascular effect of NGR-TNF.
|DCE-MRI Demonstration of Antivascular Effects of
Combretastatin A4 Phosphate (CA4P) Given in Combination with Bevacizumab
to Human Subjects with Advanced Solid Tumours
Anwar R. Padhani1, Dow-Mu Koh2, NJ Jane Taylor1, James J. Stirling1, David J. Collins2, Gordon J. Rustin1, Adrian Harris3, R Sinha, Jane Boxall1, J Smythe3, N Fisher4, Hillori Connors5, Ian Judson, Paul Nathan1
1Mount Vernon Cancer Centre, Northwood, UK; 2Institute of Cancer Research, Sutton, UK; 3John Radcliffe Hospital, Oxford, UK; 4National Blood Transfusion Service, Oxford, UK; 5Oxigene Inc., Waltham, Massachusetts, USA
In this study we document reversible tumour vascular shutdown following the first administration of the vascular disruptive agent (CA4P) and show failure of recovery of tumour vasculature when CA4P is given with the anti-VEGF antibody bevacizumab. Marked heterogeneity in individual lesion responses were seen but cohort analysis convincingly shows failure of tumour vasculature to recover when CA4P is given with bevacizumab. This is the first mechanistic demonstration in humans of increased anti-vascular action of CA4P and bevacizumab using DCE-MRI.
MR Perfusions Imaging of Anti Angiogenic (Bevacizumab)
Treatment in Patients with Recurrent High Grade Gliomas
Bob Lei Hou1, Sasan Karimi2, Lauren E. Abrey2, Andrei I. Holodny2, Philip H. Gutin2
1MSKCC, New York City, USA; 2MSKCC, New York City, New York, USA
Anti-angiogenic therapy using bevacizumab (Avastin) affects abnormal neovascularity of high grade primary brain tumors. We used DCE and DSE perfusion techniques on 9 patients with recurrent high grade gliomas before and after the first cycle of bevacizumab. Mean bolus wash-in slopes, Ktrans, fBV, and rCBV ratios for the 9 patients decreased respectively from 2.07+/-1.77 to 0.84+/-0.85, 1.86 +/-0.80 to 1.26+/-0.21, 1.83 +/-0.85 to 1.36+/-0.71, and 1.92+/-0.99 to 1.20+/-0.28. Ktrans ratio (p=0.043) and bolus wash-in slopes (p=0.015) before and after treatment were significantly different suggesting the bolus wash-in slope from DCE perfusion is the most sensitive parameter for tumor vessel changes.
Apparent Diffusion Coefficients Show Good
Reproducibility But Heterogeneous Change in Response to Treatment with
Combrestation A4 Phosphate (CA4P) and Bevacizumab in Patients with Solid
Abdominal and Pelvic Tumours
Dow-Mu Koh1, 2, Anwar Padhani3, Matthew Blackledge4, Ben Wilton4, David J. Collins4, Toni Wallace2, N J. Taylor3, James J. Stirling3, Rajesh Sinha2, Hillori Connors5, Martin O. Leach4, Ian Judson4, Paul Nathan6
1Institute of Cancer Research, Sutton, UK; 2Royal Marsden Hospital, Sutton, UK; 3Mount Vernon Hospital, UK; 4Institute of Cancer Research, Sutton, UK; 5Oxigene Inc, USA; 6Mount Veron Hospital, UK
The aims of this study were to determine the ADC measurement variability in a two centre clinical trial, and to track ADC changes in response to the administration of the vascular disrupting drug Combrestatin A4 phosphate (CA4P) and the anti-VEGF antibody bevacizumab. We found that ADC showed excellent reproducibility. However, mean ADC values proved to be insensitive to treatment related effects in our study and bio-informatics based approaches to data analysis should be developed.