**4. Representative cases**

### **4.1. Patient 1**

The first patient is a 48-year-old right handed gentleman who presented to hospital after sustaining a fall. A CT head was performed that revealed a 1.9 × 2.0 cm ring-enhancing lesion in the left cingulum with significant amount of surrounding edema (**Figure 1**). On initial evaluation, patient had 4/5 right hand weakness and right-sided pronator drift that improved with initiation of steroids. The lesion was located immediately below the paracentral lobule, and given its proximity to this eloquent area, a needle biopsy with subsequent laser ablation was offered to the patient, who agreed to proceed. The lesion was treated using two trajectories using a side-firing laser (Monteris) to ensure the full tumor volume was included within blue thermal threshold treatment lines. Postoperatively, his neurological exam remained stable with the exception of the transient neglect of right lower extremity. Pathology of the tumor was consistent with glioblastoma. Molecular analysis demonstrated negative staining for IDH-1 and p53, intact 1p/19q, and non-amplified EGFR. Proliferative index was moderate with Ki-67 about 9–10%. The patient underwent subsequent concurrent chemotherapy and radiation according to the Stupp protocol followed by twenty-two cycles of temozolomide. Following that, he was followed with regular MRI brain scans that demonstrated a significant decrease in the size of the lesion over the first 12 months. It remains stable without evidence of recurrence or progression 6 years after the initial procedure (**Figure 1**).

### **4.2. Patient 2**

The second patient is a 66-year-old right handed woman who was evaluated for spells of dizziness and visual disturbance. Brain imaging demonstrated a homogenously enhancing right parahippocampal lesion measuring 1.2 × 0.9 cm with surrounding edema (**Figure 2**). Patient

thermotherapy affects tumor cells that results in enhanced sensitivity to radiation [8]. Glioma stem cell (GSC) cultures and mice bearing glioma xenographs were first exposed to 42°C for 1 h followed by radiation. When compared to radiation or hyperthermia alone, glioma stem cells are most significantly affected when both modalities are used in combination. Exposure of GSC to heat and radiation reduced stem cell survival, proliferation, and DNA repair, as well as promoted cell death. On the molecular level, there was significantly less AKT phosphorylation in cells exposed to hyperthermia and radiation, and rescuing AKT phosphorylation levels reversed negative effects of heat and radiation maintaining viability of tumor stem cells. Furthermore, exposing the mice bearing glioma xenographs to hyperthermia and radiation consistently reduced tumor size in these animals, and significantly increased their survival compared to animals exposed to either hyperthermia or radiation alone. These results add further evidence that the addition of hyperthermia to the standard radiation treatment may have a significant additive effect with respect to tumor control that is mediated by altering phosphorylation levels of PI3K-AKT pathway. Thus, early radiation therapy after laser ablation procedure may have additive effect on controlling tumor growth and affecting glioma cell viability. Further studies are needed to explore the clinical potential of this combined treatment.

The first patient is a 48-year-old right handed gentleman who presented to hospital after sustaining a fall. A CT head was performed that revealed a 1.9 × 2.0 cm ring-enhancing lesion in the left cingulum with significant amount of surrounding edema (**Figure 1**). On initial evaluation, patient had 4/5 right hand weakness and right-sided pronator drift that improved with initiation of steroids. The lesion was located immediately below the paracentral lobule, and given its proximity to this eloquent area, a needle biopsy with subsequent laser ablation was offered to the patient, who agreed to proceed. The lesion was treated using two trajectories using a side-firing laser (Monteris) to ensure the full tumor volume was included within blue thermal threshold treatment lines. Postoperatively, his neurological exam remained stable with the exception of the transient neglect of right lower extremity. Pathology of the tumor was consistent with glioblastoma. Molecular analysis demonstrated negative staining for IDH-1 and p53, intact 1p/19q, and non-amplified EGFR. Proliferative index was moderate with Ki-67 about 9–10%. The patient underwent subsequent concurrent chemotherapy and radiation according to the Stupp protocol followed by twenty-two cycles of temozolomide. Following that, he was followed with regular MRI brain scans that demonstrated a significant decrease in the size of the lesion over the first 12 months. It remains stable without evidence

of recurrence or progression 6 years after the initial procedure (**Figure 1**).

The second patient is a 66-year-old right handed woman who was evaluated for spells of dizziness and visual disturbance. Brain imaging demonstrated a homogenously enhancing right parahippocampal lesion measuring 1.2 × 0.9 cm with surrounding edema (**Figure 2**). Patient

**4. Representative cases**

196 Glioma - Contemporary Diagnostic and Therapeutic Approaches

**4.1. Patient 1**

**4.2. Patient 2**

**Figure 1.** Representative axial T1-weighted MRI images obtained post gadolinium contrast administration. (A) Preoperative; (B) at 24 h post laser ablation; (C) at 3 months; (D) at 1 year; and (E) at 6 years post laser ablation; (F) a corresponding T2 weighted axial slice demonstrating very limited amount of edema surrounding the lesion.

**Figure 2.** Representative MRI images of the right temporal lesion of patient 2. Axial T1-weighted MR images following contrast administration. The patient originally presented with a right mesial homogenously enhancing lesion (A). Immediately following laser ablation the characteristics of the lesion changed with markedly less contrast uptake (B). In the subsequent months, the lesion has continued to involute and significantly decreased in size at 3 months (C), and almost disappeared completely at 2.5 years (D).

was started on Keppra. Laser ablation of the lesion with a concurrent biopsy was recommended given the deep-seated location of the tumor. A single trajectory was used employing a side firing laser (Monteris). Complete tumor coverage was achieved as indicated by inclusion of the entire tumor volume within the blue thermal damage threshold lines. She had an uneventful postoperative course. No new postoperative deficits were associated with the procedure. Pathology showed a hypercellular glial tumor with marked nuclear atypia, frequent mitoses, and vascular proliferative changes, consistent with the diagnosis of glioblastoma. A Ki-67 labeling index in excess of 30% was focally noted. Greater than 80% of tumor cells stained positively with antibody to p53. 1p/19q chromosomes were intact, and EGFR was non-amplified. Following laser treatment, the patient received chemotherapy and radiation according to Stupp protocol, followed by adjuvant temozolomide for eight cycles that was stopped due to persistent myelosuppression. She was followed with regular MRI scans of brain with great local control with nearly complete resolution of the treated lesion. Unfortunately, at 2.5 years after procedure she developed disease progression at a remote site.

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