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A critical point in the treatment of lymphoma and also testicular cancer is the detection of residual tumor mass after finishing chemotherapy. In the final examination computerized tomography (CT) scan finds residual tumor mass in 40-60% of patients with Hodgkin disease, non-Hodgkin lymphoma and testicular cancer, but only 15-20% of these patients will relapse.
It is the question if there is vital tumor tissue in the residual mass or necrosis or fibrosis. In each case we must come to a decision whether the patient needs further treatment or only follow-up. For patients with nonseminomatous testicular cancer, the resection of the residual lesion is standard. Patients with seminoma and lymphoma were mostly controlled with CT scan or positron emission tomography (PET). CT scan shows only the size of the residual mass and has a rather low specificity. In contrast, positron emission tomography (PET) visualizes the glucose metabolism of the tissue and improves differentiation between vital and avital tumor tissue in residual masses. Contrast-enhanced ultrasound (CEUS) is also a functional imaging test and detects the vascularization of a tissue. There are a few small studies about CEUS in the evaluation of treatment response. They show a decrease in contrast uptake if the chemotherapy or molecularly targeted treatment was effective.
The purpose of this study was to receive first insights into the diagnostic accuracy of CEUS in the evaluation of residual lesions after treatment for malignant lymphoma and testicular cancer. For response evaluation, the patients of the study received B-mode sonography first. In case of residual mass immediately CEUS was performed and the contrast enhancement was evaluated. A high contrast enhancement indicated a high vascularity in the residual mass and was interpreted as the presence of vital tumor tissue in the residual lesion and the presence of active disease. No contrast enhancement indicated a low or no vascularity and was seen as a sign for avital tissue and the absence of active disease. The patients with low enhancement were first examined carefully but at last viewed as no contrast enhancement. Histology of the residual lesion was performed in several patients. All remaining patients were examined every three months with sonography, CT scan, sometimes PET with a follow-up for a minimum of 12 months. Both were taken as the reference standard to judge the presence of vital tumor issue within the residual lesion indicating active disease after treatment and the need for further treatment.
To determine the diagnostic accuracy, we compared the results of CEUS with the reference standard and calculated the sensitivity, specificity, likelihood ratios and the predictive values.
The calculated value of sensitivity and the negative predictive value (NPV) are satisfactory, so that an investigation with an adequate power seems useful. If the results are confirmed in larger studies, the high NPV would suggest the possibility to perform first CEUS in patients with residual tumor mass. Then, in case of high contrast enhancement further diagnostic as PET or biopsy of the residual lesion should be performed. In case of no contrast enhancement the patients should be observed with CEUS. By using this approach it will be possible to reduce the exposition to radiation for the patient and in addition to save costs.
Our study has considerable limitations. Nevertheless, in our opinion the data shows that an investigation with an adequate power seems useful. Therefore, we calculated the sample size which is needed for a study to receive an adequate power.
One of the main disadvantages of ultrasound is that the result depends on the investigator. This is why we destined the agreement of two judges in terms of the contrast enhancement. In our study the agreement between two investigators is good/substantial.