Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose.

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established. Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome. Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival. Results: The median follow- up time for the entire cohort was 10.33 months (1.25-97.28). The overall median survival was 12.5months (95%CI = 5.8-19.2), with 53.3%, and 35.8% surviving at 1- and 2- years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI = 1.4-6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12-16 Gy can expect shorter LPFS than those receiving 18-20 Gy (HR = 1.7, 95% CI = 1.0-2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5-4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival. Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

Image fusion of fluid-attenuated inversion recovery magnetic resonance imaging sequences for surgical image guidance.

BACKGROUND: Nonenhancing brain lesions can be relatively poorly defined on volumetric data sets routinely used for surgical guidance. Fluid-attenuated inversion recovery MRI sequences can provide better margin visualization of nonenhancing or poorly enhancing lesions. METHODS: Using image fusion programs, we combined data sets of SPGR imaging pulse sequence or volumetric CT with volumetrically acquired FLAIR sequences and subsequently used the fused data set for image-guided surgery. This technique was used in 50 surgical cases. Of these, 9 were nonenhancing intrinsic brain tumors, 13 were partially enhancing tumors, and 11 were enhancing tumors. In addition, FLAIR fusion was selectively used for 6 nontumoral lesions and in 11 nonlesional epilepsy surgery cases. RESULTS: Image guidance using the fused data set was accurate in all 50 cases. Despite the lack of enhancement, 3 of the 9 nonenhancing tumors were found to be high grade. One of the low-grade tumors was associated with considerable areas of gliotic change not considered to represent tumor on permanent histology. In all other cases, the FLAIR-bright resected margins were consistent with tumor, not gliosis. Radical resection (>95% volume) was achieved in 21 of 23 tumor cases in which this had been the preoperative intent. CONCLUSIONS: Nonenhancing lesions are often poorly demarcated not only on imaging studies, but also during surgery. Fluid-attenuated inversion recovery fusion allows resection of such lesions using intraoperative computer image guidance. Complementary FLAIR information can also occasionally be useful during surgical approaches to enhancing lesions or in nontumor cases. It must be kept in mind that FLAIR has high sensitivity but low specificity. Fluid-attenuated inversion recovery abnormalities do not obviate the need for mapping in potentially functional areas.

In vivo accuracy of image guidance performed using optical tracking and optimized registration.

OBJECT: Image guidance systems involving the use of frameless referencing of surgical space to compile volumetric imaging data sets recently have come into widespread use. Few studies have addressed the true intraoperative surgical accuracy (that is, the application accuracy) of these systems except in a subjective manner. Calculated accuracies given by the systems do not necessarily reflect true intraoperative accuracy. METHODS: To objectively assess the stereotactic accuracy of a frameless image guidance system using optical spatial referencing, the author analyzed postoperative magnetic resonance (MR) images after placement of depth electrodes for the investigation of epilepsy. Preoperative planning for the treatment of seven patients included implanting skull fiducial screws and obtaining computed tomography/MR fusion images by using ImMerge image fusion software on the StealthStation (Medtronic, Inc.). A total of 42 electrodes were placed. Postoperative volumetric MR images were fused with preoperative study images. The difference between the planned electrode trajectories and targets and the visualized electrodes was measured in stereotactic space. CONCLUSIONS: The mean distance between the distal electrode contact and the distal end of the planned trajectory for the 42 targets was 3 +/- 1.5 mm. The most common error was in depth. The author's technique did not involve rigid skull fixation of electrodes because they were subsequently tunneled subcutaneously and later removed at the bedside of the patient. Errors in depth were known to be due to traction at the time of tunneling and not due to stereotactic factors. Correcting for depth along the electrode trajectory, the mean accuracy was found to be 2.4 +/- 1 mm.

Quantification of true in vivo (application) accuracy in cranial image-guided surgery: influence of mode of patient registration.

OBJECTIVE: Very few studies have attempted to quantify the true (application) accuracy of image-guidance systems during craniotomy. This is, in part, because of the lack of millimetric intraoperative targets to allow such measurements. Few in vivo studies have compared the influence of mode of patient registration on subsequent true accuracy. METHODS: Seven modes of patient registration (anatomic landmarks, 5 or 10 adhesive fiducials, bone-implanted fiducials [Stryker-Leibinger], surface matching using 45 or 100 points over scalp convexity or nose/auditory meatus contours) were compared. Thirty patients were involved in the study. Millimetric targets (bone drill holes or deep 1-mm titanium hemoclips) were placed then localized and saved at surgery. These targets were then identified on postoperative volumetric computed tomography fused with operative data sets. Localization errors of the targets were measured for each registration on an optical image-guidance system (StealthStation). RESULTS: Only implanted cranial fiducials had a statistically significant accuracy advantage (1.7 +/- 0.7 mm). All other registrations had similar accuracies (approximately 4.0 +/- 1.7 mm) except anatomic landmarks, which were worse (4.8 +/- 1.9 mm). Calculated accuracies (root mean squared) had no predictive value for true (application) accuracies. CONCLUSION: Not surprisingly, application accuracy of image-guidance is worse without implanted cranial markers. Unexpectedly, there was no major difference in localization of deep targets between the other registrations tested in this study. Care must be taken when using image-guidance tools to consider error introduced by registration. Cranium-implanted fiducials should be considered when high accuracy and reproducibility are needed.

Category-specific cortical mapping: color-naming areas.

OBJECT: It has been hypothesized that a certain degree of specialization exists within language areas, depending on some specific lexical repertories or categories. To spare hypothetical category-specific cortical areas and to gain a better understanding of their organization, the authors studied patients who had undergone electrical stimulation mapping for brain tumors and they compared an object-naming task with a category-specific task (color naming). METHODS: Thirty-six patients with no significant preoperative language deficit were prospectively studied during a 2-year period. Along with a reading task, both object- and color-naming tasks were used in brain mapping. During color naming, patients were asked to identify 11 visually presented basic colors. The modality specificity of the color-naming sites found was subsequently tested by asking patients to retrieve the color attributes of objects. High individual variability was observed in language organization among patients and in the tasks performed. Significant interferences in color naming were found in traditional language regions-that is, Broca (p < 0.003) and Wernicke centers (p = 0.05)--although some color-naming areas were occasionally situated outside of these regions. Color-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Anatomical segregation of the different naming categories was apparent in 10 patients; in all, 13 color-specific naming areas (that is, sites evoking no object-naming interference) were detected in the dominant-hemisphere F3 and the supramarginal, angular, and posterior parts of the temporal gyri. Nevertheless, no specific brain region was found to be consistently involved in color naming (p > 0.05). At five sites, although visually presented color-naming tasks were impaired by stimulation, auditory color naming (for example, "What color is grass?") was performed with no difficulty, showing that modality-specific areas can be found during naming. CONCLUSIONS: Within language areas, a relative specialization of cortical language areas for color naming can be found during electrical stimulation mapping.

Comparison of magnetic tracking and optical tracking by simultaneous use of two independent frameless stereotactic systems.

OBJECTIVE: The goal of this study was to compare the calculated accuracy and the true surgical accuracy of a magnetic and an optical tracking system at surgical registration and during surgery. METHODS: Two Food and Drug Administration-approved, commercially available frameless stereotactic systems were used simultaneously in 70 surgical cases. The Compass Cygnus-PFS system (Compass International, Rochester MN) uses magnetic field referencing and tracking. The StealthStation (Medtronic SNT, Louisville, CO) uses optical referencing and tracking. Registration was performed for each of the systems using adhesive fiducial markers, cranial-implanted markers, anatomic landmarks, or a combination thereof. Preoperative imaging consisted of volumetric computed tomography, magnetic resonance imaging, or both. Calculated accuracy was given by each of the systems as the root mean square after registration. Surgical accuracy was assessed by comparing the anatomic accuracy of each system with a number of recognizable intraoperative anatomic landmarks. RESULTS: Calculated accuracy (root mean square) was 1.4 +/- 0.6 mm using the magnetic system and 1.4 +/- 0.8 mm using the optical tracking system. In the 42 patients with implanted cranial fiducials, the calculated accuracies were 1.0 +/- 0.5 mm (magnetic) and 0.9 +/- 0.4 mm (optical). True surgical accuracy was considered good (3 mm or less) in both systems in 60 of 70 patients. In two patients, neither system was accurate. In eight patients, one of the two systems was considered inaccurate. Of these, the magnetic system was considered inaccurate three times and the optical system five times. CONCLUSION: Magnetic referencing and tracking was found to be comparable with optical tracking both with regard to calculated and true surgical accuracy. Interference from metal objects in the magnetic field was seen rarely.

Intra-operative mapping of cortical areas involved in reading in mono- and bilingual patients.

In order to identify the cortical areas involved in the reading process and to spare them during surgery, we systematically studied cortical areas by direct cortical stimulation in patients operated on for brain tumours. Seventy-six cortical stimulation mapping studies for language were performed in 35 monolingual and 19 bi- or multilingual patients over a 5-year period. We systematically searched for reading interference areas in addition to standard naming areas using an 'awake surgery' technique for brain mapping. A 'reading aloud' task (translated into different languages in multilingual patients) was used. Brain mapping was performed in left (44 patients) and right (10 patients) hemispheres. Cortical areas involved in reading were identified according to the type of interference, location and distinctness from naming areas. Stimulation of several major hemispheric regions resulted in significant interference with reading aloud: (i) the lower part of the pre- and postcentral gyri (P < 0.00001); (ii) the dominant supramarginal, angular and the posterior part of the superior temporal gyri (P < 0.00001); (iii) in the dominant inferior and middle frontal gyri (P < 0.001); and (iv) in the posterior part of the dominant middle temporal gyrus (P < 0.05). Interferences in reading were generally found in small cortical areas, with intervening areas evoking no reading interferences. Only partial overlap between reading and naming sites was found. Reading-specific sites were preferentially found when stimulating dominant inferior parietal or posterior temporal areas. Different types of reading interferences were noted. While 'articulatory' interferences were found in pre- and postcentral gyri bilaterally, and ocular-induced movements in bilateral middle frontal gyri, paraphasias were found mainly in the dominant supramarginal and posterior superior temporal gyri. Reading arrest sites were found in many regions. Reading interference sites were also occasionally found in the non-dominant hemisphere. In bilingual patients, if common cortical areas could be found, language- and reading-specific areas were sometimes detected, lending support to the concept that bilinguals can have relatively distinct cortical representation of their language skills. Finally, in this series, the location of reading interference sites and their relative specialization showed considerable individual variability.