Single slice dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) appears to provide perfusion data about sarcomas in vivo that correlate with tumor necrosis on equivalent pathological sections. However, sarcomas are heterogeneous and therefore single slice DCE-MRI may not correlate with total tumor necrosis.
To determine whether changes in pharmacokinetic modeling of DCE-MRI, during chemotherapy for primary bone sarcomas correlated with histological measures of total tumor necrosis.
Twelve patients with appendicular primary bone sarcomas were included in the study. Each patient had DCE-MRI before, and after completion, of pre-operative chemotherapy. The mean arterial slope (A), endothelial permeability coefficient (K(trans)), and extravascular extracellular volume (V(e)) were derived from each data set using a modified two compartment pharmacokinetic model. Total tumor necrosis rates were compared with changes in A, K(trans), and V(e).
Six patients had total tumor necrosis of >or=90% and six had a measure of <90%. The median percentage changes in A, K(trans), and V(e) for the >or=90% necrosis group were -52.5% (-83 to 6), -66% (-82 to 26), and 23.5% (-26 to 40), respectively. For the <90% necrosis group, A = - 35% (-75 to 132), K(trans)= - 53 (-66 to 149) and V(e)= - 14.5% (-42 to 40). One patient with >90% necrosis had increases in all three measures. Comparison of the two groups generated P-values of 0.699 for A, 0.18 for K(trans), and 0.31 for V(e).
There was no statistically significant correlation between changes in pharmacokinetic perfusion parameters and total tumor necrosis. When using single slice DCE-MRI heterogeneous histology of primary bone sarcomas and repair mediated angiogenesis might both be confounding factors.
[Show abstract][Hide abstract] ABSTRACT: The prognostic and predictive value of magnetic resonance (MR) investigations in clinical oncology may be improved by implementing strategies for discriminating between viable and necrotic tissue in tumors. The purpose of this preclinical study was to investigate whether the extent of necrosis in tumors can be assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and/or T(2)-weighted MR imaging.
Three amelanotic human melanoma xenograft lines differing substantially in tumor necrotic fraction, necrotic pattern, extracellular volume fraction, and blood perfusion were used as experimental models of human cancer. MRI was performed at 1.5 T and a spatial resolution of 0.23 × 0.47 × 2.0 mm(3). Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) was used as contrast agent. Plots of Gd-DTPA concentration versus time were generated for each voxel, and three parameters were calculated for each curve: the extracellular volume fraction (ν(e)), the final slope (a), and the Gd-DTPA concentration at one minute after the contrast administration (C(1min)). Parametric images of ν(e), a, C(1min), and the signal intensity in T(2)-weighted images (SI(T2W)) were compared with the histology of the imaged tissue.
The ν(e), a, and C(1min) frequency distributions were significantly different for necrotic and viable tissue in all three tumor lines. By using adequate values of ν(e), a, and C(1min) to discriminate between necrotic and viable tissue, significant correlations were found between the fraction of necrotic tissue assessed by MRI and the fraction of necrotic tissue assessed by image analysis of histological preparations. On the other hand, the SI(T2W) frequency distributions did not differ significantly between necrotic and viable tissue in two of the three tumor lines.
Necrotic regions in tumor tissue can be identified in parametric images derived from DCE-MRI series, whereas T(2)-weighted images are unsuitable for detection of tumor necrosis.
[Show abstract][Hide abstract] ABSTRACT: Standard therapy for localized osteosarcoma includes neoadjuvant chemotherapy preceding local control surgery, followed by adjuvant chemotherapy. When limb-salvage procedures were being developed, preoperative chemotherapy allowed a delay in definitive surgery to permit fabrication of custom endoprosthetic reconstruction implants. One rationale for its continuation as the care standard has been the perception that it renders surgery easier and safer. Our objective was to compare surgical procedures planned on the basis of magnetic resonance images (MRIs) of distal femoral osteosarcomas acquired before neoadjuvant chemotherapy with surgical procedures planned on the basis of MRIs acquired after neoadjuvant chemotherapy as a measure of the surgically critical anatomic effects of the chemotherapy.
Twenty-four consecutive patients with distal femoral osteosarcoma had available digital MRIs preceding and following neoadjuvant chemotherapy. Thorough questionnaires were used to catalogue surgically critical anatomic details of MRI-directed surgical planning. Four faculty musculoskeletal oncologic surgeons and two musculoskeletal radiologists evaluated the blinded and randomly ordered MRIs. Interrater and intrarater reliabilities were calculated with intraclass correlation coefficients. The Student t test and chi-square test were used to compare pre-chemotherapy and post-chemotherapy continuous and categorical variables on the questionnaire. Mixed-effect regression models were employed to compare surgical procedures planned on the basis of pre-chemotherapy MRIs and with those planned on the basis of post-chemotherapy MRIs.
The blinded reviews generated strong intraclass correlation coefficients for both interrater (0.772) and mean intrarater (0.778) reliability. The MRI-planned resections for the majority of tumors changed meaningfully after chemotherapy, but in inconsistent directions. On the basis of mixed-effect regression modeling, it appeared that more amputations were planned on the basis of post-chemotherapy MRIs. No other parameters differed in a significant and clinically meaningful fashion. Surgeons demonstrated their expectation that neoadjuvant chemotherapy would improve resectability by planning more radical surgical procedures on the basis of scans that they predicted had been obtained pre-chemotherapy.
Surgeons can reliably record the anatomic details of a planned resection of an osteosarcoma. Such methods may be useful in future multi-institutional clinical trials or registries. The common belief that neoadjuvant chemotherapy increases the resectability of extremity osteosarcomas remains anecdotally based. Rigorous assessment of this phenomenon in larger cohorts and at other anatomic sites as well as re-evaluation of other arguments for neoadjuvant chemotherapy should be considered.
The Journal of Bone and Joint Surgery 08/2012; 94(15):1399-405. DOI:10.2106/JBJS.K.00971 · 5.28 Impact Factor
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