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OBJECTIVE:: We investigate the patterns of failure in the treatment of glioblastoma (GBM) based on clinical target volume (CTV) margin size, dose delivered to the site of initial failure, and the use of temozolomide and intensity-modulated radiotherapy (IMRT). METHODS:: Between August 2000 and May 2010, 161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide. Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique. Patterns of failure and time to progression and overall survival were compared based on CTV margin, use of temozolomide, and use of IMRT. Kaplan Meier analysis was used to estimate survival times, and χ test was used for comparison of cohorts. RESULTS:: For patients treated with 5-, 10-, and 15- to 20-mm CTV, 79%, 77%, and 86% experienced failures in the 60 Gy volume, respectively. Forty-eight percent, 55%, and 66% of patients with 5-, 10-, and 15- to 20-mm CTV experienced failures in the 46 Gy volume, respectively. There was no statistical difference between patients treated with 5-, 10-, 15- to 20-mm margins with regard to 60 Gy failure (P=0.76), 46 Gy failure (P=0.51), or marginal failure (P=0.73). Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume. There was no increased likelihood of marginal failures in patients receiving IMRT (P=0.97). CONCLUSIONS:: Modern treatment techniques including use of concurrent temozolmide, limited CTV margin size, and IMRT have not greatly changed the patterns of failure of GBM.

Overall survival of patients with brain metastases has improved in the past decade.1,2 Such improvement can often be offset by the late toxicities of whole-brain radiotherapy (WBRT), for which the likelihood and severity of cognitive decline continues to worsen with time.3 Multiple randomized trials have now shown that using radiosurgery as an upfront single modality and without WBRT does not affect overall survival in select patients.4,5 However, there are patients who will experience early or multiple distant brain failures, and these patients will likely need WBRT earlier in the course of their disease. As a result, an increasing emphasis is being placed on prognostic factors that may distinguish populations that benefit more from upfront radiosurgery from those that may benefit from upfront WBRT. Recent data from the scientific literature have suggested that the natural history of brain metastases can depend on the histological subtype of the primary cancer. Some histologies such as renal cell carcinoma have proved more radioresistant.6 Even for tumors of the same primary histology, such as invasive ductal carcinoma of the breast, there can be variability in the natural history of brain metastases depending on the Her2 receptor status of the individual patient’s cancer.7 It has been suggested that patients with melanoma and triple-negative breast cancers may have higher rates of distant brain failure after radiosurgery.8,9 Within lung cancer, there are several known differences between the various histological subtypes with regard to the natural history of the disease. Small cell lung cancer (SCLC) has a high rate of metastatic brain disease, and prophylactic cranial irradiation has in fact resulted in survival benefits both in limited- and extensive-stage disease.10,11 Adenocarcinoma appears to have a survival advantage over squamous cell carcinoma (SCC) within the non-small cell subtypes in the setting of locally advanced disease.12 It has been previously unknown, however, whether biological differences in various subtypes of lung cancer affect the biological behavior of brain metastases. Objectives To this end, we present a single-institution retrospective review of patients with lung cancer and first diagnosis of brain metastases treated with Gamma Knife radiosurgery (GKRS) and without previous therapeutic WBRT. Our analysis focuses on variations of clinical outcomes caused by histological differences of the primary cancer. Furthermore, we evaluate factors that may predict survival, distant brain failure, and neurological death.

BACKGROUND It has been well established that Gamma Knife radiosurgery (GKS) is an effective treatment for brain arteriovenous malformations (AVMs). OBJECTIVE To evaluate complete obliteration rates for magnetic resonance imaging (MRI)-based GKS treatment planning performed with and without angiography and to conduct a preliminary assessment of the utility of using pulsed arterial spin labeling (PASL) magnetic resonance (MR) perfusion imaging to confirm complete obliteration. METHODS Forty-six patients were identified who had undergone GKS without embolization with a minimum follow-up of 2 years. One group was planned with integrated stereotactic angiography and MR (spoiled gradient recalled) images obtained on the day of GKS. A second technique avoided the risk of arteriography by using only axial MR images. Beginning in 2007, PASL MR perfusion imaging was routinely performed as a portion of the follow-up MRI to assess the restoration of normal blood flow of the nidus and surrounding area. RESULTS The overall obliteration rate for the angiography/MRI group was 88.0% (29 of 33). Patients in the MRI-only group had an obliteration rate of 61.5% (8 of 13), with P=.092 with the Fisher exact test, which is not statistically significant. A Kaplan-Meier analysis was also not statistically significant (log rank test, P=.474). Four of 9 patients with incomplete obliteration on angiography also had shown residual abnormal blood flow on PASL imaging. CONCLUSION This retrospective analysis shows that treatment planning technique used in GKS does not play a role in the eventual obliteration of treated AVMs. PASL may have potential in the evaluation of AVM obliteration.