After the institution of the current standard of care for high-grade gliomas, abnormal increase of the enhancing portion of the lesion was observed. According to the McDonald criteria, this could have represented recurrence. However, patients did not get clinically worse. In fact, this increase of the enhancing portion of the lesion could have been something besides neoplasm. Follow-up MR imaging exams demonstrated that this enhancing area spontaneously decreased without any change in the treatment regimen. This is called pseudoprogression, and it is a major and challenging clinical decision regarding the patient’s life! Its diagnosis can only be achieved with prospective interpretation. This situation poses an important question when considering the clinical management of patients: what does the increasing enhancing portion of the treated lesion really mean?

Changes in the enhancing portion of treated high-grade gliomas may not represent tumor recurrence when it increases, or even a good response when it reduces. Actually, the enlargement of the enhancing area may not be related to a poor prognosis but to a good treatment response. Thus, it is unnecessary to change the treatment to second-line drugs or even to perform a new surgical intervention. Similarly, anti-angiogenic drugs significantly reduce the area of enhancement shortly after their use, with no proven antitumor effect at that time. However, the reduction of the enhancement does not signal a good treatment response.

Based on these observations, it became clear that new tumor treatment response criteria would be necessary to meet these needs.

Since our team has seriously devoted itself to the analysis of these patients and this article has been published, we have received correspondence from other groups involved in the treatment of patients with brain tumors that have the same questions and anxieties regarding this challenging topic. We have sought to follow these patients more closely. Thus, we have been trying to find ways to help us make clinical decisions when the imaging changes cause doubts about the success of the therapy.

We are always prospectively collecting information within a multidisciplinary team so we can create a database to better analyze our results.

To this data we are adding information about the genetic profile of each neoplasia. We believe that the genetic data involved in the analysis of brain tumors will be essential in therapeutic decision-making, individualizing it and making the interpretation of imaging findings easier and, at the same time, challenging. We are enthusiastic about the application of multiparametric techniques in these cases, especially DSC sequences with histogram evaluation in cases of pseudoprogression. In cases with pseudoresponse, diffusion has been shown to be useful in identifying areas of tumor progression before areas of contrast impregnation. In special cases where the areas of restricted diffusion do not evolve, proton spectroscopy has helped us in this evaluation and differentiation.

We are still collecting data and finalizing the analysis. We hope that we can present our data as soon as possible, preferably at meetings in the neuroimaging and neuro-oncology areas (e.g., American Society of Neuroradiology and American Society of Clinical Oncology) that emphasize the challenges posed by posttherapeutic changes in brain neoplasm.

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