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Letters to the Editor |
Department of Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Editor:
In the January 1999 issue of Radiology, Dr Postema and colleagues (1) determined the value of dynamic magnetic resonance (MR) imaging to assess tumor aggressiveness in International Federation of Gynecology and Obstetrics (FIGO) stage I or II cervical carcinoma. Dr Postema and colleagues conclude that dynamic MR imaging has a limited role in assisting in treatment decisions for early-stage disease (90% of the patients had stage I–IIA disease) since they did not observe significant differences in dynamic MR imaging parameters in tumors with or without lymph node spread. This observation supports our findings that in early-stage disease, no important associations can be made between dynamic MR imaging parameters and lymph node infiltration (2).
However, our concept for advanced-stage (FIGO stages IIB–IVA) disease is to use lymphatic channel invasion rather than lymph node status as an important predictor of tumor biologic aggressiveness in correlation with tissue exchange rate data (k21). The reason to use lymphatic channel invasion as an important predictor of tumor biologic aggressiveness is twofold: the growth of tumor cells within a lymph node occurs via the lymphatic vessels, and the data drawn from the literature (3) show that lymphatic channel invasion is a strong and independent predictor of tumor recurrence and patient survival. In general, there is a decrease in the overall 5-year survival rate of approximately 50% in patients with cervical carcinoma when lymphatic channel invasion has occurred. These observations are substantiated by the recent results by Schlenger et al (3), which show that lymphatic channel invasion is an important predictor of disease-free survival in advanced-stage disease. Using this approach, we found important associations between lymphatic channel invasion and a fast tissue exchange rate constant k21 in advanced disease.
Dr Postema and colleagues performed dynamic MR imaging by injecting gadopentetate dimeglumine as a bolus, and the maximum slope and amplitude were quantified for data analysis. From our histopathologic correlations with MR imaging, we concluded that the maximum slope approach mainly reflects microvascular perfusion. In contrast, our approach (2) of a constant infusion of gadopentetate dimeglumine in conjunction with a pharmacokinetic model calculating for the tissue exchange rate constant k21 estimates microvascular permeability rather than perfusion. We focus more on the assessment of microvascular permeability, since evidence strongly suggests that angiogenic activity is not only expressed in the number of vessels but also reflected in the permeability of tumor vessels.
That dynamic MR imaging has an important role in assessing tumor aggressiveness in advanced cervical carcinoma is supported by the exciting findings of Mayr et al (4). The data of this group suggest that dynamic MR imaging parameters may be used early during a course of radiation therapy to predict local tumor control.
In conclusion, my colleagues and I believe that there is a great need to define and carefully standardize dynamic MR imaging protocols. Which method will best fit the need to assess tumor microcirculation has to be clarified in multicenter studies. It is well conceivable that using gray-scale dynamic MR images alone is not sufficient for data evaluation, since great variations in the spatial and temporal distribution of microcirculation, which have to be accounted for, are reported to be present in a variety of tumors. Such future protocols should strictly standardize all aspects of dynamic data acquisition, especially data evaluation.
References
Department of Radiology, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, the Netherlands*; and Erasmus University Medical Center Rotterdam, the Netherlands
We thank Dr Hawighorst for his comments with regard to our article (1). In his letter, Dr Hawighorst draws attention to his group's interesting work on the use of dynamic MR imaging in advanced stages of cervical carcinoma. Experimental work by his group suggests that lymphatic channel invasion as a marker of tumor biologic aggressiveness in advanced disease can be quantified with dynamic MR imaging. This is in contrast with our findings in patients with early-stage cervical carcinoma (1), in whom dynamic MR imaging seems not to reflect tumor aggressiveness. Because the casual reader might erroneously perceive a discrepancy here, we would like to clarify this point.
In our article, we focus on the use of dynamic MR imaging in early-stage FIGO I or IIA cervical cancer, with special emphasis on how MR imaging could affect clinical management. Adding dynamic MR imaging to the staging protocol, it was hoped, might make a difference with regard to treatment decisions. Under the current preoperative staging scheme, patients with clinical FIGO stages I and IA are eligible for radical surgery, and patients with advanced stages IIB-IV will undergo primary radiation therapy. Now, the problem is that about half the patients who undergo surgery will be subjected to additional radiation therapy in the immediate postoperative period. These patients are then exposed to the inconvenience, hazards, and coexistent morbidity of double treatment, whereas in fact they would have been better off with primary radiation therapy alone. Additional radiation therapy is usually given whenever histopathologic findings during surgery indicate that (a) histologic tumor invasion depth is 15 mm or more and/or (b) pelvic lymph node metastasis is present.
The rationale of our study was to see whether, in patients who are eligible for surgery, those women who required additional radiation therapy could be identified preoperatively with dynamic MR imaging. If so, then dynamic MR imaging may be useful as a test to avoid unwanted surgery. Unfortunately, in the 62 consecutive patients with FIGO stage I or IIA cervical carcinoma in our study, neither a nor b was depicted accurately with dynamic MR imaging.
Dr Hawighorst argues that the failure of dynamic MR imaging to predict tumor biologic aggressiveness in our study could be explained by the fact that we used an MR imaging protocol that differed from his. While one can never exclude such a possibility (we discuss this in our article), we consider this unlikely. We did find a considerable and significant difference between dynamic MR imaging parameters of carcinoma versus those of surrounding tissues, which indicate that our MR imaging method accurately reflected tumor angiogenesis. We should point out that our findings agreed with those of Dr Hawighorst and co-workers. As Dr Hawighorst concedes in his letter, his group also did not find an important association between dynamic MR imaging parameters and lymph node infiltration in patients with early-stage disease (2).
References
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