Clinical study of apatinib plus temozolomide for the treatment of recurrent high-grade gliomas.

OBJECTIVES: Recurrent high-grade glioma, a malignant tumor of the brain or spinal cord associated with poor prognosis with a median survival of <6 months. Recurrent high-grade glioma does not have standard treatment even if some strategies have some effect in recurrent gliomas. Apatinib, as a tyrosine kinase inhibitor shown to be effective in treating the lung and gastric cancer. The present study investigated the efficacy and safety of apatinib in combination with dose-dense regimens of temozolomide for treating recurrent glioma. PATIENTS AND METHODS: Eighteen patients with recurrent high-grade glioma were enrolled and treated with apatinib (500 mg/day) and TMZ (50 mg/m2/day). Patients who achieved partial response or stable disease continued treatment. Administration of drug was terminated for patients with progressive disease, who could not tolerate toxicity, and who required discontinuation due to other medical conditions. RESULTS: From the 18 cases, only 17 were included in the evaluation of the curative effect of the drug and in that four showed partial responses, ten had stable disease, remaining three exhibited progressive disease. The disease control rate was 82.3% (14/17). Progression-free and overall survival was found to be 4 months and 9.1 months, respectively. Three patients became transiently capable of self-care (Karnofsky performance status >70). Cognition and quality of life improved after treatment and from the safety perspective, three most common adverse reactions included epilepsy (24.1%), hypertension (20.7%), and fatigue (17.2%). CONCLUSION: Apatinib and TMZ may represent an alternative treatment option for patients with recurrent high-gradeglioma, especially those with a low Karnofsky performance status. However, studies using a larger sample size are required to confirm these findings.

Parenteral high­dose ascorbate - A possible approach for the treatment of glioblastoma (Review).

For glioblastoma, the treatment with standard of care therapy comprising resection, radiation, and temozolomide results in overall survival of approximately 14-18 months after initial diagnosis. Even though several new therapy approaches are under investigation, it is difficult to achieve life prolongation and/or improvement of patient's quality of life. The aggressiveness and progression of glioblastoma is initially orchestrated by the biological complexity of its genetic phenotype and ability to respond to cancer therapy via changing its molecular patterns, thereby developing resistance. Recent clinical studies of pharmacological ascorbate have demonstrated its safety and potential efficacy in different cancer entities regarding patient's quality of life and prolongation of survival. In this review article, the actual glioblastoma treatment possibilities are summarized, the evidence for pharmacological ascorbate in glioblastoma treatment is examined and questions are posed to identify current gaps of knowledge regarding accessibility of ascorbate to the tumor area. Experiments with glioblastoma cell lines and tumor xenografts have demonstrated that high­dose ascorbate induces cytotoxicity and oxidative stress largely selectively in malignant cells compared to normal cells suggesting ascorbate as a potential therapeutic agent. Further investigations in larger cohorts and randomized placebo­controlled trials should be performed to confirm these findings as well as to improve delivery strategies to the brain, through the inherent barriers and ultimately to the malignant cells.

Maximal surgical resection and adjuvant surgical technique to prolong the survival of adult patients with thalamic glioblastoma.

The importance of maximal resection in the treatment of glioblastoma (GBM) has been reported in many studies, but maximal resection of thalamic GBM is rarely attempted due to high rate of morbidity and mortality. The purpose of this study was to investigate the role of surgical resection in adult thalamic glioblastoma (GBM) treatment and to identify the surgical technique of maximal safety resection. In case of suspected thalamic GBM, surgical resection is the treatment of choice in our hospital. Biopsy was considered when there was ventricle wall enhancement or multiple enhancement lesion in a distant location. Navigation magnetic resonance imaging, diffuse tensor tractography imaging, tailed bullets, and intraoperative computed tomography and neurophysiologic monitoring (transcranial motor evoked potential and direct subcortical stimulation) were used in all surgical resection cases. The surgical approach was selected on the basis of the location of the tumor epicenter and the adjacent corticospinal tract. Among the 42 patients, 19 and 23 patients underwent surgical resection and biopsy, respectively, according to treatment strategy criteria. As a result, the surgical resection group exhibited a good response with overall survival (OS) (median: 676 days, p < 0.001) and progression-free survival (PFS) (median: 328 days, p < 0.001) compared with each biopsy groups (doctor selecting biopsy group, median OS: 240 days and median PFS: 134 days; patient selecting biopsy group, median OS: 212 days and median PFS: 118 days). The surgical resection groups displayed a better prognosis compared to that of the biopsy groups for both the O6-methylguanine-DNA methyltransferase unmethylated (log-rank p = 0.0035) or methylated groups (log-rank p = 0.021). Surgical resection was significantly associated with better prognosis (hazard ratio: 0.214, p = 0.006). In case of thalamic GBM without ventricle wall-enhancing lesion or multiple lesions, maximal surgical resection above 80% showed good clinical outcomes with prolonged the overall survival compared to biopsy. It is helpful to use adjuvant surgical techniques of checking intraoperative changes and select the appropriate surgical approach for reducing the surgical morbidity.

Regional deep hyperthermia in combination with whole brain radiotherapy (WBRT) in poor prognosis patients with brain metastases.

PURPOSE: The aim of this study is to assess for the first time, the role of regional deep hyperthermia in combination with radiotherapy and systemic therapy in patients with poor prognosis of brain metastases (GPI ≤ 2.5). METHODS: Patients with confirmed cerebral metastases and classified as GPI score ≤ 2.5 were included in this prospective study. Pretreatment stratification was defined as patients with 0-1 GPI score (Group A) and patients with 1.5-2.5 GPI score (Group B). HT was applied twice a week, 60 min per session, during RT by regional capacitive device (HY-DEEP 600WM system) at 13.56 MHz radiofrequency. RESULTS: Between June 2015 and June 2017, 15 patients and a total of 49 brain metastases were included in the protocol. All patients received all HT sessions as planned. RT and systemic therapy were also completed as prescribed. Tolerance to treatment was excellent and no toxicity was registered. Patients with HT effective treatment time longer than the median (W90time > 88%) showed better actuarial PFS at 6 and 12 months (100% and 66.7%, respectively) compared to those with less HT effective treatment time (50% and 0%, respectively) (p < 0.031). Median OS was 6 months (range 1-36 months). Stratification by GPI score showed a median OS of 3 months (CI 95% 2.49-3.51) in Group A and 8.0 months (CI 95% 5.15-10.41) in Group B (p = 0.035). CONCLUSIONS: Regional hyperthermia is a feasible and safe technique to be used in combination with RT in brain metastases patients, improving PFS and survival in poor prognostic brain metastasis patients.

Anti-PD-1 Immunotherapy in Preclinical GL261 Glioblastoma: Influence of Therapeutic Parameters and Non-Invasive Response Biomarker Assessment with MRSI-Based Approaches.

Glioblastomas (GBs) are malignant brain tumours with poor prognosis even after aggressive therapy. Programmed cell death-1 (PD-1) immune checkpoint blockade is a promising strategy in many types of cancer, but its therapeutic effects in GB remain low and associated with immune infiltration. Previous work suggests that oscillations of magnetic resonance spectroscopic imaging (MRSI)-based response pattern with chemotherapy could act as a biomarker of efficient immune system attack onto GBs. The presence of such oscillations with other monotherapies such as anti-PD-1 would reinforce its monitoring potential. Here, we confirm that the oscillatory behaviour of the response biomarker is also detected in mice treated with anti PD-1 immunotherapy both in combination with temozolomide and as monotherapy. This indicates that the spectral pattern changes observed during therapy response are shared by different therapeutic strategies, provided the host immune system is elicited and able to productively attack tumour cells. Moreover, the participation of the immune system in response is also supported by the rate of cured animals observed with different therapeutic strategies (in the range of 50-100% depending on the treatment), which also held long-term immune memory against tumour cells re-challenge. Taken together, our findings open the way for a translational use of the MRSI-based biomarker in patient-tailored GB therapy, including immunotherapy, for which reliable non-invasive biomarkers are still missing.

Management of glioblastoma: State of the art and future directions.

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.

Permanent iodine-125 brachytherapy for patients with progressive or recurrent high-grade gliomas.

BACKGROUND: The prognosis of patients with progressive or recurrent high-grade gliomas (HGGs) after surgery remains poor. Iodine-125 brachytherapy is emerging as a salvage method for the treatment of gliomas. This study aimed to investigate whether permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection. METHODS: Between March 2004 and August 2016, 58 patients with progressive or recurrent HGG after gross total resection were included in this study. Twenty-nine patients underwent radiotherapy and/or chemotherapy and then permanent iodine-125 brachytherapy (SRCI group). Twenty-nine patients underwent permanent iodine-125 brachytherapy alone (SI group). Follow-up was carried out at 1, 3, and 6 months and then at 1, 2, 3, and 5 years after iodine-125 implantation. The median overall survival (OS) and progression-free survival (PFS), procedure-related complications and clinical outcomes were evaluated. RESULTS: No procedure-related fatal events happened. The temporary morbidity rate was 11.9%. The median OS and PFS for patients in the SI group were 22 and 8 months compared with 21 and 7 months in the SRCI group. No significant differences were found. Age and Karnofsky Performance Status (KPS) were independent prognostic factors for OS. Age, KPS and histology were independent prognostic factors for PFS. CONCLUSIONS: Permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection.

Long term follow-up and outcomes in adult patients with thalamic gliomas.

OBJECTIVES: To investigate the optimal treatment and prognosis of thalamic glioma in adult patients. PATIENTS AND METHODS: We retrospectively analyzed the adult patients with thalamic glioma admitted to our hospital from May 2005 to September 2016. Patients were divided into two groups according to their treatment: surgery-based combined treatment and intensity modulated radiation therapy (IMRT)-based treatment. Univariate chi-square test and multivariate logistic regression were used to identify independent factors for the treatment modality. A log-rank test, adjusting for propensity score, was used to compare the overall survival (OS) and progression-free survival (PFS) of patients between the two groups. RESULTS: Fifty-eight adult patients with thalamic gliomas were included in the analysis. Of them, 31 were treated with surgery-based treatment, and 27 were treated with IMRT-based treatment. The overall survival (OS) and progression-free survival (PFS) of patients between the two groups were not significantly different (median OS 16.0 (range 1.0-163.0) months vs. 10.0 (range 1.0-118.0) months, p = 0.344 and median PFS 10.0 (range 1.0-163.0) months vs. 6.0 (range 1.0-118.0) months, p = 0.464, respectively) even after adjusting for potential confounding factors. CONCLUSIONS: The OS and PFS of adult patients with thalamic glioma were not significantly different between patients in the surgical group and in the IMRT group. IMRT might be an acceptable alternative to surgery for adult patients with unresectable thalamic glioma.

Laser interstitial thermal therapy for in-field recurrence of brain metastasis after stereotactic radiosurgery: does treatment with LITT prevent a neurologic death?

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.

Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008-2016.

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.

The role of neutrophil-to-lymphocyte ratio in predicting overall survival in patients undergoing laser interstitial thermal therapy for glioblastoma.

Laser interstitial thermal therapy (LITT) offers a minimally-invasive treatment option for glioblastomas (GBM) which are relatively small or in eloquent areas. While laser ablation for malignant gliomas has been shown to be safe and effective, the role of the subsequent immune response in not well established. In this study we aim to analyze the prognostic potential of edema volume and acute inflammation, quantified as neutrophil-to-lymphocyte ratio (NLR), in predicting overall survival. Twenty-one patients were identified with new or recurrent GBMs that were candidates for LITT. Laser ablation was performed using standard solid tumor protocol for treatment volume, intensity and duration. Edema volume was quantified using MRI imaging, while retrospective chart review was performed to calculate NLR and survival. In patients treated with LITT for GBM, peri-tumoral vasogenic edema volumes did not significantly change post-operatively, p > 0.200, while NLR significantly increased, p = 0.0002. The degree of NLR increase correlated with longer overall survivals, and ROC analysis demonstrated an area under the curve of 0.827, p = 0.0112. A delta-NLR cutoff of 7.0 results in positive and negative predictive values of 78% and 75%, respectively, in predicting overall survival >1 year. Patients with with delta-NLR > 7.0 lived significantly longer that those with delta-NLR < 7.0, median survival 440 days compared to 239 days, p = 0.0297. We demonstrate preliminary data that monitoring the inflammatory response after LITT in GBM patients offers a potential prognostic measurement to assist in predicting treatment efficacy and overall survival.

Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma.

PURPOSE: In the EF-14 trial for newly diagnosed glioblastoma (ndGBM) patients addition of Tumour Treating Fields (TTFields) to temozolomide treatment resulted in a significantly improved overall survival (OS). In the NOA-09/CeTeG trial, combination of lomustine and temozolomide was superior to temozolomide monotherapy in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter methylated (MGMTm) ndGBM. We evaluated combination of these two treatment modalities in patients with MGMTm ndGBM. There have been so far no data on the combination of these two efficient regimens. METHODS: This bicentric retrospective analysis investigated 16 patients. Parameters evaluated included safety outcome as measured by Common Toxicity Criteria for Adverse Events (CTCAE), clinical outcomes, and compliance to treatment. RESULTS: Hematologic adverse events CTCAE ≥ 3 were observed in seven, hepatotoxic adverse events of CTCAE ≥ 3 in four patients. Mild to moderate skin toxicity was detected in six patients. At data cutoff, patients demonstrated a median progression-free survival (PFS) of 20 months. The usage rate of TTFields showed a high median adherence (83%) to the therapy. CONCLUSIONS: This analysis provides first indication that the combination of TTFields/lomustine/temozolomide is safe and feasible. The observed survival outcomes might suggest potential beneficial effects.

System-based approaches as prognostic tools for glioblastoma.

BACKGROUND: The evasion of apoptosis is a hallmark of cancer. Understanding this process holistically and overcoming apoptosis resistance is a goal of many research teams in order to develop better treatment options for cancer patients. Efforts are also ongoing to personalize the treatment of patients. Strategies to confirm the therapeutic efficacy of current treatments or indeed to identify potential novel additional options would be extremely beneficial to both clinicians and patients. In the past few years, system medicine approaches have been developed that model the biochemical pathways of apoptosis. These systems tools incorporate and analyse the complex biological networks involved. For their successful integration into clinical practice, it is mandatory to integrate systems approaches with routine clinical and histopathological practice to deliver personalized care for patients. RESULTS: We review here the development of system medicine approaches that model apoptosis for the treatment of cancer with a specific emphasis on the aggressive brain cancer, glioblastoma. CONCLUSIONS: We discuss the current understanding in the field and present new approaches that highlight the potential of system medicine approaches to influence how glioblastoma is diagnosed and treated in the future.

Nutrition & Exercise Interventions in Pediatric Patients with Brain Tumors: A Narrative Review.

Brain tumors have been the most common pediatric solid tumor and leading cause of morbidity and mortality. Improved survival emphasizes the importance of adverse treatment effects especially related to nutrition and exercise. Although studies have examined nutrition and exercise outcomes, few randomized trials exist. This narrative review included a systematic literature search with analysis of controlled or single group studies examining clinical and quality-of-life impact of nutrition or exercise interventions. Seven articles were included. Three nutrition studies demonstrated improvement with proactive feeding tubes, nutritional supplementation, and nutritional status. Two exercise studies showed improvement in measures of fitness and neuroanatomy with exercise in pediatric brain tumor survivors; two cohort studies demonstrated a link between quality of life and physical activity. Preliminary studies show nutrition and exercise may improve physical well-being and quality of life, suggesting future controlled studies are warranted to inform clinical care of children with brain tumors.

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy.

BACKGROUND: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT). METHODS: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). RESULTS: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. CONCLUSIONS: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

A feasibility study of the Nativis Voyager® device in patients with recurrent glioblastoma in Australia.

AIM: Evaluation of the Nativis Voyager®, an investigational medical device, as monotherapy for recurrent glioblastoma (rGBM). MATERIALS & METHODS: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months. RESULTS: Median overall survival was 8.04 months in the A1A arm and 6.89 months in the A2HU arm. No serious adverse events associated with Voyager were reported. No clinically relevant trends were noted in clinical laboratory parameters or physical exams. CONCLUSION: The data suggest that the Voyager is safe and feasible for the treatment of rGBM.

Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, and Outcomes.

BACKGROUND: Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking. OBJECTIVE: To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes. METHODS: We performed a retrospective descriptive study of patients with histologically proven GBM who underwent LITT. Data collected included demographics, tumor location and volume, tumor genetic markers, treatment volume, perioperative complications, and long-term follow-up data. RESULTS: We performed 58 LITT treatments for GBM in 54 patients over 5.5 yr. Forty-one were recurrent tumors while 17 were frontline treatments. Forty GBMs were lobar in location, while 18 were in deep structures (thalamus, insula, corpus callosum). Average tumor volume was 12.5 ± 13.4 cm3. Average percentage of tumor treated with the yellow thermal damage threshold (TDT) line (dose equivalent of 43°C for 2 min) was 93.3% ± 10.6%, and with the blue TDT line (dose equivalent of 43°C for 10 min) was 88.0% ± 14.2%. There were 7 perioperative complications (12%) and 2 mortalities (3.4%). Median overall survival after LITT for the total cohort was 11.5 mo, and median progression-free survival 6.6 mo. CONCLUSION: LITT appears to be a safe and effective treatment for GBM in properly selected patients.

Breast cancer patients with brain metastasis undergoing GKRS.

BACKGROUND: Breast cancer (BC) is the second most common cause of brain metastasis in the United States. Compared to whole brain radiation therapy (WBRT), treatment with gamma-knife radiosurgery (GKRS) offers a better chance at neurocognitive preservation. The goal of our retrospective study is to report the overall survival (OS) in patients receiving GKRS and to identify factors that improve survival outcomes. METHODS: The records of 80 patients with primary BC treated with GKRS at the Yale Comprehensive Cancer Center between 2000 and 2013 were reviewed. OS was calculated from the date of first GKRS treatment. Other factors studied were age, Karnofsky performance status (KPS), tumor subtype, having WBRT and/or surgical resection pre- or post-GKRS, and number of brain metastases treated with GKRS. RESULTS: Median age was 56.2 years. OS from first GKRS was 13.1 months (95% CI 7.6-21.9). On univariate analysis, improved survival was associated with HER-2 subtype (p = 0.026), KPS score > 80 (p = 0.009), and good control of systemic disease at time of GKRS (p = 0.020). Multivariable analysis detected a significantly longer survival with HER-2 positivity (HR 0.22, 95% CI 0.06-0.76, p = 0.017) and a strong trend in patients with craniotomy prior to GKRS (HR 0.13, 95% CI 0.01-1.11, p = 0.06). CONCLUSIONS: GKRS is a promising therapy for treating brain metastasis from BC, particularly in those with HER-2 positivity and high-performance scores even in those patients with > 5 brain metastases. Furthermore, GKRS may also be a useful adjunct to surgical resection in such patients. High rates of neurological death remain from BC brain metastases; however, and need further investigation.