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Hirotaka Hasegawa, Shunya Hanakita, Masahiro Shin, Mariko Kawashima, Taichi Kin, Wataru Takahashi, Yuichi Suzuki, Yuki Shinya, Hideaki Ono, Masaaki Shojima, Hirofumi Nakatomi and Nobuhito Saito

OBJECTIVE

In Gamma Knife radiosurgery (GKS) for arteriovenous malformations (AVMs), CT angiography (CTA), MRI, and digital subtraction angiography (DSA) are generally used to define the nidus. Although the AVM angioarchitecture can be visualized with superior resolution using rotational angiography (RA), the efficacy of integrating RA into the GKS treatment planning process has not been elucidated.

METHODS

Using data collected from 25 consecutive patients with AVMs who were treated with GKS at the authors’ institution, two neurosurgeons independently created treatment plans for each patient before and after RA integration. For all patients, MR angiography, contrasted T1 imaging, CTA, DSA, and RA were performed before treatment. The prescription isodose volume before (PIVB) and after (PIVA) RA integration was measured. For reference purposes, a reference target volume (RTV) for each nidus was determined by two other physicians independent of the planning surgeons, and the RTV covered by the PIV (RTVPIV) was established. The undertreated volume ratio (UVR), overtreated volume ratio (OVR), and Paddick’s conformal index (CI), which were calculated as RTVPIV/RTV, RTVPIV/PIV, and (RTVPIV)2/(RTV × PIV), respectively, were measured by each neurosurgeon before and after RA integration, and the surgeons’ values at each point were averaged. Wilcoxon signed-rank tests were used to compare the values obtained before and after RA integration. The percentage change from before to after RA integration was calculated for the average UVR (%ΔUVRave), OVR (%ΔOVRave), and CI (%ΔCIave) in each patient, as ([value after RA integration]/[value before RA integration] − 1) × 100. The relationships between prior histories and these percentage change values were examined using Wilcoxon signed-rank tests.

RESULTS

The average values obtained by the two surgeons for the median UVR, OVR, and CI were 0.854, 0.445, and 0.367 before RA integration and 0.882, 0.478, and 0.463 after RA integration, respectively. All variables significantly improved after compared with before RA integration (UVR, p = 0.009; OVR, p < 0.001; CI, p < 0.001). Prior hemorrhage was significantly associated with larger %ΔOVRave (median 20.8% vs 7.2%; p = 0.023) and %ΔCIave (median 33.9% vs 13.8%; p = 0.014), but not %ΔUVRave (median 4.7% vs 4.0%; p = 0.449).

CONCLUSIONS

Integrating RA into GKS treatment planning may permit better dose planning owing to clearer visualization of the nidus and, as such, may reduce undertreatment and waste irradiation. Further studies examining whether the observed RA-related improvement in dose planning also improves the radiosurgical outcome are needed.

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Randy S. Bell, Chris J. Neal and Randall McCafferty

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Seyed Amir Javadi and Mehdi Zeinalizadeh

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Hussein Fathalla, Ahmed Ashry and Ahmed El-Fiki

OBJECTIVE

Managing penetrating military brain injuries in a war zone setting is different than managing common civilian penetrating brain injuries. Triage, i.e., deciding on which patients to treat or not treat, and which to be flown back home, is essential to avoid wasting valuable limited resources. In this study the authors aim to identify reliable predictors of mortality and poor outcome to help develop a protocol for treating their patients in the battlefield. They also demonstrate all the lessons learned from their collective experience regarding some of the controversial management issues.

METHODS

This study was a retrospective review of 102 patients with penetrating military missile head injuries treated by the authors in various facilities in northern Sinai between 2011 and 2018. Patient demographics, clinical characteristics, imaging characteristics, postoperative complications, and Glasgow Outcome Scale (GOS) scores were recorded for each patient. Several variables associated with mortality and poor outcome that were derived from the literature were analyzed, in addition to variables obtained by direct observation by the authors over time.

RESULTS

There were 50 patients (49%) with GOS score of 1 (death), 12 patients (11.8%) with GOS score of 2 (survivors in persistent vegetative state), and 40 survivors (39.2%) with varying degrees of disability on the last follow-up evaluation. The authors identified an anatomical danger zone that was found to predict mortality when traversed. Bilateral dilated fixed pupils and low Glasgow Coma Scale score on admission were also found to be independent predictors of mortality and poor outcome. Based on these findings, a protocol was developed for managing these patients in the war zone.

CONCLUSIONS

Managing military penetrating head injuries in the war zone is different than civilian gunshot head injuries encountered by most neurosurgeons in urban cities. The authors developed a simple protocol for managing military penetrating injuries in the war zone. They also describe important lessons learned from this experience.

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Dusan Urgosik and Roman Liscak

OBJECTIVE

Ablative procedures are still useful in the treatment of intractable pain despite the proliferation of neuromodulation techniques. In the paper the authors present the results of Gamma Knife thalamotomy (GKT) in various pain syndromes.

METHODS

Between 1996 and 2016, unilateral GKT was performed in 30 patients suffering from various severe pain syndromes in whom conservative treatment had failed. There were 20 women and 10 men in the study population, with a median age of 80 years (range 53–89 years). The pain syndromes consisted of 8 patients with classic treatment-resistant trigeminal neuralgia (TN), 6 with postherpetic TN, 5 with TN and constant pain, 1 with TN related to multiple sclerosis, 3 with trigeminal neuropathic pain, 4 with thalamic pain, 1 with phantom pain, 1 with causalgic pain, and 1 with facial pain. The median follow-up period was 24 months (range 12–180 months). Invasive procedures for pain release preceded GKT in 20 patients (microvascular decompression, glycerol rhizotomy, balloon microcompression, Gamma Knife irradiation of the trigeminal root, and radiofrequency thermolesion). The Leksell stereotactic frame, GammaPlan software, and T1- and T2-weighted sequences acquired at 1.5 T were used for localization of the targeted medial thalamus, namely the centromedian (CM) and parafascicularis (Pf) nucleus. The CM/Pf complex was localized 4–6 mm lateral to the wall of the third ventricle, 8 mm posterior to the midpoint, and 2–3 mm superior to the intercommissural line. GKT was performed using the Leksell Gamma Knife with an applied dose ranging from 145 to 150 Gy, with a single shot, 4-mm collimator. Pain relief after radiation treatment was evaluated. Decreased pain intensity to less than 50% of the previous level was considered successful.

RESULTS

Initial successful results were achieved in 13 (43.3%) of the patients, with complete pain relief in 1 of these patients. Relief was achieved after a median latency of 3 months (range 2–12 months). Pain recurred in 4 (31%) of 13 patients after a median latent interval of 24 months (range 22–30 months). No neurological deficits were observed.

CONCLUSIONS

These results suggest that GKT in patients suffering from severe pain syndromes is a relatively successful and safe method that can be used even in severely affected patients. The only risk of GT for the patients in this study was failure of treatment, as no clinical side effects were observed.

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Takashi Shuto, Atsuya Akabane, Masaaki Yamamoto, Toru Serizawa, Yoshinori Higuchi, Yasunori Sato, Jun Kawagishi, Kazuhiro Yamanaka, Hidefumi Jokura, Shoji Yomo, Osamu Nagano and Hidefumi Aoyama

OBJECTIVE

Previous Japanese Leksell Gamma Knife Society studies (JLGK0901) demonstrated the noninferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for patients with 5–10 brain metastases (BMs) compared with those with 2–4 BMs in terms of overall survival and most secondary endpoints. The authors studied the aforementioned treatment outcomes in a subset of patients with BMs from non–small cell lung cancer (NSCLC).

METHODS

Patients with initially diagnosed BMs treated with SRS alone were enrolled in this prospective observational study. Major inclusion criteria were the existence of up to 10 tumors with a maximum diameter of less than 3 cm each, a cumulative tumor volume of less than 15 cm3, and no leptomeningeal dissemination in patients with a Karnofsky Performance Scale score of 70% or better.

RESULTS

Among 1194 eligible patients, 784 with NSCLC were categorized into 3 groups: group A (1 tumor, n = 299), group B (2–4 tumors, n = 342), and group C (5–10 tumors, n = 143). The median survival times were 13.9 months in group A, 12.3 months in group B, and 12.8 months in group C. The survival curves of groups B and C were very similar (hazard ratio [HR] 1.037; 95% CI 0.842–1.277; p < 0.0001, noninferiority test). The crude and cumulative incidence rates of neurological death, deterioration of neurological function, newly appearing lesions, and leptomeningeal dissemination did not differ significantly between groups B and C. SRS-induced complications occurred in 145 (12.1%) patients during the median post-SRS period of 9.3 months (IQR 4.1–17.4 months), including 46, 54, 29, 11, and 5 patients with a Common Terminology Criteria for Adverse Events v3.0 grade 1, 2, 3, 4, or 5 complication, respectively. The cumulative incidence rates of adverse effects in groups A, B, and C 60 months after SRS were 13.5%, 10.0%, and 12.6%, respectively (group B vs C: HR 1.344; 95% CI 0.768–2.352; p = 0.299). The 60-month post-SRS rates of neurocognitive function preservation were 85.7% or higher, and no significant differences among the 3 groups were found.

CONCLUSIONS

In this subset analysis of patients with NSCLC, the noninferiority of SRS alone for the treatment of 5–10 versus 2–4 BMs was confirmed again in terms of overall survival and secondary endpoints. In particular, the incidence of neither post-SRS complications nor neurocognitive function preservation differed significantly between groups B and C. These findings further strengthen the already-reported noninferiority hypothesis of SRS alone for the treatment of patients with 5–10 BMs.

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Alana Tooze and Jason P. Sheehan

OBJECTIVE

Pituitary adenomas and the treatment required for the underlying neuropathology have frequently been associated with cognitive dysfunction. However, the mechanisms for these impairments remain the subject of much debate. The authors evaluated cognitive outcomes in patients treated with or without Gamma Knife radiosurgery (GKRS) for an underlying pituitary adenoma.

METHODS

This was a retrospective, institutional review board–approved, single-institution study. A total of 51 patients (23 male, 28 female) treated for pituitary adenoma were included in this neurocognitive study. Twenty-one patients underwent GKRS following transsphenoidal surgery, 22 patients were treated with transsphenoidal surgery alone, and eight patients were conservatively managed or were treated with medical management alone. Comparisons using psychometric tests of general intellectual abilities, memory, and executive functions were made between the treatment groups, between male and female patients, and between patients with Cushing’s disease and those with nonfunctioning adenoma (NFA).

RESULTS

The entire patient sample, the NFA group, and the GKRS group scored significantly below expected on measures of both immediate and delayed memory, particularly for visually presented information (p ≤ 0.05); however, there were no significant differences between the patients with Cushing’s disease and those with NFA (t ≤ 0.56, p ≥ 0.52). In those who underwent GKRS, memory scores were not significantly different from those in the patients who did not undergo GKRS (t ≤ 1.32, p ≥ 0.19). Male patients across the sample were more likely to demonstrate impairments in both immediate memory (t = −3.41, p = 0.003) and delayed memory (t = −3.80, p = 0.001) than were female patients (t ≤ 1.09, p ≥ 0.29). There were no impairments on measures of general intellectual functioning or executive functions in any patient group. The potential contributions of tumor size and hormone levels are discussed.

CONCLUSIONS

Overall, pituitary adenoma patients demonstrated relative impairment in anterograde memory. However, GKRS did not lead to adverse effects for immediate or delayed memory in pituitary adenoma patients. Cognitive assessment of pituitary adenoma patients is important in their longitudinal care.

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Alexis Dimitriadis and Ian Paddick

OBJECTIVE

Stereotactic radiosurgery (SRS) is characterized by high levels of conformity and steep dose gradients from the periphery of the target to surrounding tissue. Clinical studies have backed up the importance of these factors through evidence of symptomatic complications. Available data suggest that there are threshold doses above which the risk of symptomatic radionecrosis increases with the volume irradiated. Therefore, radiosurgical treatment plans should be optimized by minimizing dose to the surrounding tissue while maximizing dose to the target volume. Several metrics have been proposed to quantify radiosurgical plan quality, but all present certain weaknesses. To overcome limitations of the currently used metrics, a novel metric is proposed, the efficiency index (η50%), which is based on the principle of calculating integral doses: η50% = integral doseTV/integral dosePIV50%.

METHODS

The value of η50% can be easily calculated by dividing the integral dose (mean dose × volume) to the target volume (TV) by the integral dose to the volume of 50% of the prescription isodose (PIV50%). Alternatively, differential dose-volume histograms (DVHs) of the TV and PIV50% can be used. The resulting η50% value is effectively the proportion of energy within the PIV50% that falls into the target. This value has theoretical limits of 0 and 1, with 1 being perfect. The index combines conformity, gradient, and mean dose to the target into a single value. The value of η50% was retrospectively calculated for 100 clinical SRS plans.

RESULTS

The value of η50% for the 100 clinical SRS plans ranged from 37.7% to 58.0% with a mean value of 49.0%. This study also showed that the same principles used for the calculation of η50% can be adapted to produce an index suitable for multiple-target plans (Gη12Gy). Furthermore, the authors present another adaptation of the index that may play a role in plan optimization by calculating and minimizing the proportion of energy delivered to surrounding organs at risk (OARη50%).

CONCLUSIONS

The proposed efficiency index is a novel approach in quantifying plan quality by combining conformity, gradient, and mean dose into a single value. It quantifies the ratio of the dose “doing good” versus the dose “doing harm,” and its adaptations can be used for multiple-target plan optimization and OAR sparing.

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Bengt Karlsson, Arne V. Johansson, Huai-Che Yang, Hidefumi Jokura, Masaaki Yamamoto, Roberto Martínez-Álvarez, Jun Kawagishi, Wan-Yuo Guo, Guus Beute, David H. C. Pan, Wen-Yuh Chung, Michael Söderman, Hitoshi Aiyama and Tseng Tsai Yeo

OBJECTIVE

There is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.

METHODS

The present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.

RESULTS

The age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25–60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.

CONCLUSIONS

The present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.