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Letters to the Editor |
Department of Radiology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
e-mail: christian.kremser{at}uibk.ac.at
Editor:
We read with great interest the article by Dr Sahani and colleagues in the March 2005 issue of Radiology (1) on the application of perfusion computed tomography (CT) to assess treatment response in rectal cancer. This article describes a study using first-pass perfusion CT to prospectively investigate tumor vascularity in rectal cancer. Perfusion CT was performed in 15 patients, whereby all patients underwent a standard chemotherapy and radiation therapy protocol.
Dr Sahani and colleagues found that tumors with initially higher blood flow value and lower mean transit time show poorer response to chemotherapy and radiation therapy. As their main explanation, they postulated an increase in the number of arteriovenous shunts. To further their conclusions they cite our work (2), in which we performed a similar study in patients with primary rectal carcinoma by using dynamic magnetic resonance (MR) imaging based on T1-mapping. In contrast with Dr Sahani and colleagues, we did not use an instantaneous bolus application of the contrast agent. Instead, we used a prolonged infusion of our contrast agent over a period of 4 minutes and analyzed our data by using the so-called perfusion index value, which is calculated as the ratio of maximum slope of the concentration time course of the contrast medium in tumor and the maximum of the arterial contrast medium concentration. As we pointed out in our article (2), the perfusion index value does not represent pure blood flow values but instead constitutes a combination of different parameters. Results of our most recent work, which to date includes more than 58 patients, are currently being prepared for publication and indicate that the perfusion index value is related to the transfer constant (ktrans) of the generalized kinetic model introduced by Tofts et al (3) and correlates to the permeability–surface area product. Therefore, in contradiction to the discussion by Dr Sahani and colleagues, we think that our data do not support their assumption of increased arteriovenous shunts but instead indicate a substantial role for permeability–surface area product in explaining different responses to therapy.
In the article by Wheeler et al (4) that is cited by Dr Sahani and colleagues, systemic shunting is discussed as a possible mechanism influencing response to intraarterial chemotherapy. It is important to note that the results given by Wheeler et al are not completely conclusive, since it could not be ruled out that a considerable portion of the observed shunting occurred within normal tissue. To our knowledge there is, to date, no proof that arteriovenous shunts are significantly correlated with radiation therapy outcome.
An alternative explanation for the failure of radiation therapy, which is frequently discussed in the literature, is based on hyperpermeability of tumor vessels and on the fact that well-oxygenated cells are three times more susceptible to radiation damage compared with hypoxic cells (5).
Hyperpermeability of tumor vessels leads to a strong coupling between capillary and interstitial flow, which causes increased interstitial pressure (6)—that is, interstitial pressure increases with increasing permeability. This increased interstitial pressure in turn causes vascular constriction and consequently reduced blood flow leading to hypoxia. We presently believe this to be consistent with the results we obtained in our studies.
The failure of Dr Sahani and colleagues to detect an influence of permeability on therapy outcome may be explained by the fact that the CT protocol that they used is not suited for the measurement of vascular permeability. It was pointed out by Miles (7) that the measurement of vascular permeability requires images to be acquired for up to 2–10 minutes, whereas the protocol by Dr Sahani and colleagues includes just 45 seconds of image acquisition.
This could also explain why no difference was detected between the permeability of normal and tumor tissue in the study by Dr Sahani and colleagues. In our own MR perfusion studies, a significant difference was found between normal and tumor tissue (8).
Altogether, the work of Dr Sahani and colleagues again shows that noninvasive assessment of microcirculatory parameters provides clinically useful information for the management of cancer, especially at a time when antiangiogenic therapies become increasingly available.
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