*2.1.1.1. Surgical treatment*

In the last decade, a great switch was produced in the therapeutical management of DA. Since it was demonstrated that these tumors have an annual linear grow of 4 mm/year on diameter [50], they are nowadays considered "infiltrating chronic disease that invades the central nervous system, that will ineluctably become malignant" [51]. It is now well established that surgery has a great impact on both the natural history and the malignant transformation. As a consequence, radical surgery becomes the goal in the treatment of diffuse gliomas in order to prevent malignant transformation and to prolong overall survival [52]. Additionally, radical surgery significantly improves seizure control compared with subtotal resection [53].

General principles of surgery, as they were underlined by Hugh Duffau, are generally accepted by the neurosurgical community: early radical surgery, awake surgery in high eloquent areas, cortical mapping, "resection according to cortico-subcortical functional and not oncological boundaries," and "multistage resection in critical regions" [51]. The most difficult part of the operation is at the boundaries of the tumor, where even with adjuvant intraoperative MRI, the distinction between normal brain and infiltrative brain is very difficult. Surgical experience contributes to better surgical results, but even in very experienced hands, there are cases in which a residual tumor could be identified on postoperative MRI (**Figure 4**).

Neuronavigation and intraoperative ultrasound are more and more used in order to improve the surgical resection, since they are able to reveal large residual tumors. Enhanced intraoperative ultrasound is at the beginning of experience, more studies being necessary to establish its usefulness in diffuse astrocytomas resection (**Figure 5**) [54].

### *2.1.1.2. Adjuvant therapy*

Factors to take into consideration for immediate postoperative therapy are those considered risk factors for worse outcome namely age > 40 years, preoperative tumor diameter > 4 cm, incomplete resection, astrocytic histology, and absence of 1p/19q codeletion [55]. In this perspective, cases with DA IDH-mut completely resected, in young patients (<40 year), are candidates for close clinical imagistic observation and no adjuvant therapy is recommended in the immediate postoperative period. However, it is expected that these tumors will recur, so additional surgical and adjuvant therapy will be added at the time of progression. For tumors with subtotal removal, in patients older than 40 years of age, immediate postoperative treatment is recommended. Concerning adjuvant radiotherapy, the recommendation is in favor of lower doses (45–50.4 Gy) which are equivalent in terms of results with the high doses (59.4–64.8 Gy) but with reduced toxicity. Relative to chemotherapeutic regimen, actual data suggest that the PCV (procarbazine, CCNU, and vincristine) formula is superior to temozolomide regimen in terms of overall survival for the treatment of DA IDH-mut, mostly in cases with codeletion of 1p/19q genes [19].

**2.2. Diffuse astrocytoma IDH wild type**

*Clinically*, their behavior is not different from the DA IDH-mut.

clinical evolutions.

postoperative CT scan (d and e).

**Definition**. This astrocytoma is a diffuse growth pattern astrocytoma without the IDH mutation. WHO 2026 lists it as a rare and provisional entity. Most tumors falling under this definition can be classified with the help of genetic testing as a variety of other entities with different

**Figure 5.** Preoperative coronal FLAIR (a), axial T2W (b) and intraoperative ultrasound examination (c) before resection of a diffuse astrocytoma subtotally removed as it is demonstrated by intraoperative ultrasound (f) and immediate

**Figure 4.** Preoperative FLAIR MR sequence (a) and immediate postoperative axial CT (b) and 3 months postoperative FLAIR examination revealing a complete removal of an insular grade II DA. (c) One year follow-up axial FLAIR MR

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management

http://dx.doi.org/10.5772/intechopen.76205

103

examination reveal complete removal of tumor with no local signs of recurrence.

The *standard MRI* findings are generally the same, the presence of a more intense enhancement suggesting an increased microvascularization and, as a consequence, a more aggressive evolution. As it was already mentioned, the presence of 2HG peak on MR spectroscopy is suggestive for IDH1 mutation, so the absence of this peak could serve as an indicator for a wild-type tumor. 2HG was also studied as a marker for the response to adjuvant therapy [56].

Diffuse Astrocytoma and Oligodendroglioma: An Integrated Diagnosis and Management http://dx.doi.org/10.5772/intechopen.76205 103

**Figure 4.** Preoperative FLAIR MR sequence (a) and immediate postoperative axial CT (b) and 3 months postoperative FLAIR examination revealing a complete removal of an insular grade II DA. (c) One year follow-up axial FLAIR MR examination reveal complete removal of tumor with no local signs of recurrence.

**Figure 5.** Preoperative coronal FLAIR (a), axial T2W (b) and intraoperative ultrasound examination (c) before resection of a diffuse astrocytoma subtotally removed as it is demonstrated by intraoperative ultrasound (f) and immediate postoperative CT scan (d and e).

### **2.2. Diffuse astrocytoma IDH wild type**

There are two entities that increase the susceptibility to diffuse astrocytomas. Low-grade astrocytomas are usually diagnosed in patients with Ollier-type multiple enchondromatosis [48]. Also, those having the Li-Fraumeni syndrome are more likely to develop diffuse gliomas, but these are high-grade anaplastic astrocytomas and high-grade glioblastomas [49].

In the last decade, a great switch was produced in the therapeutical management of DA. Since it was demonstrated that these tumors have an annual linear grow of 4 mm/year on diameter [50], they are nowadays considered "infiltrating chronic disease that invades the central nervous system, that will ineluctably become malignant" [51]. It is now well established that surgery has a great impact on both the natural history and the malignant transformation. As a consequence, radical surgery becomes the goal in the treatment of diffuse gliomas in order to prevent malignant transformation and to prolong overall survival [52]. Additionally, radical

surgery significantly improves seizure control compared with subtotal resection [53].

cases in which a residual tumor could be identified on postoperative MRI (**Figure 4**).

its usefulness in diffuse astrocytomas resection (**Figure 5**) [54].

General principles of surgery, as they were underlined by Hugh Duffau, are generally accepted by the neurosurgical community: early radical surgery, awake surgery in high eloquent areas, cortical mapping, "resection according to cortico-subcortical functional and not oncological boundaries," and "multistage resection in critical regions" [51]. The most difficult part of the operation is at the boundaries of the tumor, where even with adjuvant intraoperative MRI, the distinction between normal brain and infiltrative brain is very difficult. Surgical experience contributes to better surgical results, but even in very experienced hands, there are

Neuronavigation and intraoperative ultrasound are more and more used in order to improve the surgical resection, since they are able to reveal large residual tumors. Enhanced intraoperative ultrasound is at the beginning of experience, more studies being necessary to establish

Factors to take into consideration for immediate postoperative therapy are those considered risk factors for worse outcome namely age > 40 years, preoperative tumor diameter > 4 cm, incomplete resection, astrocytic histology, and absence of 1p/19q codeletion [55]. In this perspective, cases with DA IDH-mut completely resected, in young patients (<40 year), are candidates for close clinical imagistic observation and no adjuvant therapy is recommended in the immediate postoperative period. However, it is expected that these tumors will recur, so additional surgical and adjuvant therapy will be added at the time of progression. For tumors with subtotal removal, in patients older than 40 years of age, immediate postoperative treatment is recommended. Concerning adjuvant radiotherapy, the recommendation is in favor of lower doses (45–50.4 Gy) which are equivalent in terms of results with the high doses (59.4–64.8 Gy) but with reduced toxicity. Relative to chemotherapeutic regimen, actual data suggest that the PCV (procarbazine, CCNU, and vincristine) formula is superior to temozolomide regimen in terms of overall survival for the treatment of DA IDH-mut, mostly in cases with codeletion of

*2.1.1. Multimodal treatment*

102 Glioma - Contemporary Diagnostic and Therapeutic Approaches

*2.1.1.1. Surgical treatment*

*2.1.1.2. Adjuvant therapy*

1p/19q genes [19].

**Definition**. This astrocytoma is a diffuse growth pattern astrocytoma without the IDH mutation. WHO 2026 lists it as a rare and provisional entity. Most tumors falling under this definition can be classified with the help of genetic testing as a variety of other entities with different clinical evolutions.

*Clinically*, their behavior is not different from the DA IDH-mut.

The *standard MRI* findings are generally the same, the presence of a more intense enhancement suggesting an increased microvascularization and, as a consequence, a more aggressive evolution. As it was already mentioned, the presence of 2HG peak on MR spectroscopy is suggestive for IDH1 mutation, so the absence of this peak could serve as an indicator for a wild-type tumor. 2HG was also studied as a marker for the response to adjuvant therapy [56].
