Response of Treatment-Naive Brain Metastases to Stereotactic Radiosurgery

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions \u3e3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (\u3e1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm

Subcortical injury is an independent predictor of worsening neurological deficits following awake craniotomy procedures

Tailored craniotomies for awake procedures limit cortical exposure. Recently we demonstrated that the identification of eloquent areas increased the risk of postoperative deficits. However, it was not clear whether the observed neurological deficits were caused by proximity of functional cortex to the tumor [cortical injury] or subcortical injury. We hypothesize that subcortical injury during tumor resection is an important predictor of postoperative neurological deficits compared to cortical injury. A retrospective review of 214 patients undergoing awake craniotomy was carried out in whom preoperative functional magnetic resonance imaging (fMRI) and cortical mapping (CM) were performed. A radiologist blinded to the clinical data reviewed and graded the postoperative changes on diffusion-weighted MR-imaging (DWI). Of the 40 cases who developed new intraoperative neurological deficit, 36 (90%) occurred during subcortical dissection, 3 (7.5%) during both subcortical and cortical dissection, and 1 (2.5%) during cortical dissection. Neurological dysfunction acquired during subcortical dissection was an independent predictor of postoperative deficits both in the immediate postoperative period (P < .001) and at the 3-month follow-up (P < .001). Significant DWI restriction in the subcortical white matter was predictive of neurological deficits both immediately and at 3 months, P = .011 and P < .001, respectively. New or worsening deficits were seen in 38% of patients; however, at 3 months 13% had a mild persistent neurological deficit. Subcortical injury with significant DWI changes result in postoperative neurological decline despite our efforts to preserve cortical areas of function. This underscores the importance of preserving subcortical fiber tracts during awake craniotomy procedures

Awake craniotomy for gliomas in a high-field intraoperative magnetic resonance imaging suite: analysis of 42 cases

Object. The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex. Methods. From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome. Results. Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0-13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR >= 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%). Conclusions. There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month

Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: Case study

Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemo-therapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell count, specifically the CD4 and CD8 counts, there was no cumulative decline in the patient described in this case report. Depriving patients of this agent, in order to treat with immunotherapy, is controversial. Despite conventional dogma, we demonstrated that chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide-induced lymphopenia may prove to be synergistic with a peptide vaccine secondary to inhibition of regulatory T cells or their delayed recovery