Glioblastoma is the most common and aggressive primary brain tumor with an annual incidence of 3.19 per 100 000.^1-5 The disease course is typically rapid, with only approximately 1 in 4 patients alive 2 years after diagnosis, and only 5% to 10% of patients alive at 5 years.^1,6,7

Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Standard treatment consists of maximal safe surgical resection or a diagnostic biopsy, followed by radiotherapy (60 Gy) with concomitant daily temozolomide chemotherapy, and then maintenance treatment with temozolomide for 6 to 12 months.¹ However, most patients will die within 1 to 2 years. Median progression-free survival from diagnosis of 6.2 to 7.5 months and median overall survival from diagnosis of 14.6 to 16.7 months have been reported in clinical trials.^1-4 The reported 2- and 5-year survival rates⁵ are 27% and 10%, respectively. During the last decade, all attempts to improve the outcome for patients with glioblastoma have failed when evaluated in large randomized trials.^2-4,6,7

Purpose: Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Patients and Methods: Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test–Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Results: Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, −4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. Conclusion: Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. Patients (median age 54 years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

BACKGROUND: S100β protein is expressed constitutively by brain astrocytes. Elevated S100β levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100β also was shown to indicate blood‐brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100β reflect BBB dysfunction, parenchymal damage, or both.METHODS: The authors conducted a prospective study of serum S100β levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100β samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging.RESULTS: S100β was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100β levels (n = 45 patients; 0.16 ± 0.1 μg/L; mean ± standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 ± 0.04 μg/L). Primary brain tumors (n = 8 patients; 0.12 ± 0.08) or central nervous system metastases also presented with elevated serum S100β levels (n = 27 patients; 0.14 ± 0.34). Tumor volume was correlated with serum S100β levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 ± 0.10 μg/L) but not in patients with other brain lesions.CONCLUSIONS: S100β was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100β is a marker of BBB function. Elevated S100β levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100β as a marker for BBB function and as an early detection or follow‐up marker of brain tumors. Cancer 2003;97:2806–13. © 2003 American Cancer Society.DOI 10.1002/cncr.11409