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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.

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Constantin Tuleasca, Jean Régis, Elena Najdenovska, Tatiana Witjas, Nadine Girard, Thomas Bolton, Francois Delaire, Marion Vincent, Mohamed Faouzi, Jean-Philippe Thiran, Meritxell Bach Cuadra, Marc Levivier and Dimitri Van de Ville

OBJECTIVE

Essential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic deep brain stimulation or radiofrequency thalamotomy or, alternatively, minimally invasive techniques, including stereotactic radiosurgery (SRS) and high-intensity focused ultrasound, at the level of the ventral intermediate nucleus (Vim). The aim of the present study was to evaluate potential correlations between pretherapeutic interconnectivity (IC), as depicted on resting-state functional MRI (rs-fMRI), and MR signature volume at 1 year after Vim SRS for tremor, to be able to potentially identify hypo- and hyperresponders based only on pretherapeutic neuroimaging data.

METHODS

Seventeen consecutive patients with ET were included, who benefitted from left unilateral SRS thalamotomy (SRS-T) between September 2014 and August 2015. Standard tremor assessment and rs-fMRI were acquired pretherapeutically and 1 year after SRS-T. A healthy control group was also included (n = 12). Group-level independent component analysis (ICA; only n = 17 for pretherapeutic rs-fMRI) was applied. The mean MR signature volume was 0.125 ml (median 0.063 ml, range 0.002–0.600 ml). The authors correlated baseline IC with 1-year MR signatures within all networks. A 2-sample t-test at the level of each component was first performed in two groups: group 1 (n = 8, volume < 0.063 ml) and group 2 (n = 9, volume ≥ 0.063 ml). These groups did not statistically differ by age, duration of symptoms, baseline ADL score, ADL point decrease at 1 year, time to tremor arrest, or baseline tremor score on the treated hand (TSTH; p > 0.05). An ANOVA was then performed on each component, using individual subject-level maps and continuous values of 1-year MR signatures, correlated with pretherapeutic IC.

RESULTS

Using 2-sample t-tests, two networks were found to be statistically significant: network 3, including the brainstem, motor cerebellum, bilateral thalamus, and left supplementary motor area (SMA) (pFWE = 0.004, cluster size = 94), interconnected with the red nucleus (MNI −2, −22, −32); and network 9, including the brainstem, posterior insula, bilateral thalamus, and left SMA (pFWE = 0.002, cluster size = 106), interconnected with the left SMA (MNI 24, −28, 44). Higher pretherapeutic IC was associated with higher MR volumes, in a network including the anterior default-mode network and bilateral thalamus (ANOVA, pFWE = 0.004, cluster size = 73), interconnected with cerebellar lobule V (MNI −12, −70, −22). Moreover, in the same network, radiological hyporesponders presented with negative IC values.

CONCLUSIONS

These findings have clinical implications for predicting MR signature volumes after SRS-T. Here, using pretherapeutic MRI and data processing without prior hypothesis, the authors showed that pretherapeutic network interconnectivity strength predicts 1-year MR signature volumes following SRS-T.

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Herwin Speckter, Jose Bido, Giancarlo Hernandez, Diones Rivera, Luis Suazo, Santiago Valenzuela, Isidro Miches, Jairo Oviedo, Cesar Gonzalez and Peter Stoeter

OBJECTIVE

The goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).

METHODS

In 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5–63.3 months).

RESULTS

Several DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).

CONCLUSIONS

DTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

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Veronica L. Chiang, Samuel T. Chao, Constantin Tuleasca, Matthew C. Foote, Cheng-chia Lee, David Mathieu, Hany Soliman and Arjun Sahgal

In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.

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Masaaki Yamamoto, Toru Serizawa, Yoshinori Higuchi, Osamu Nagano, Hitoshi Aiyama, Takao Koiso, Shinya Watanabe, Takuya Kawabe, Yasunori Sato and Hidetoshi Kasuya

OBJECTIVE

With the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)–BSBM.

METHODS

For this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998–2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM.

RESULTS

Two factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299–1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078–1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4–5, the score is either 4 or 5; for ES-BSBM 2–3, the score is either 2 or 3; and for ES-BSBM 0–1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4–19.3) in ES-BSBM 4–5, 6.9 (95% CI 6.4–7.4) in ES-BSBM 2–3, and 2.8 (95% CI 2.5–3.6) in ES-BSBM 0–1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2–23.4), 7.9 (95% CI 7.4–8.5), and 3.2 (95% CI 2.8–3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older.

CONCLUSIONS

The authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

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Marc Levivier, Rafael E. Carrillo, Rémi Charrier, André Martin and Jean-Philippe Thiran

OBJECTIVE

The authors developed a new, real-time interactive inverse planning approach, based on a fully convex framework, to be used for Gamma Knife radiosurgery.

METHODS

The convex framework is based on the precomputation of a dictionary composed of the individual dose distributions of all possible shots, considering all their possible locations, sizes, and shapes inside the target volume. The convex problem is solved to determine the plan, i.e., which shots and with which weights, that will actually be used, considering a sparsity constraint on the shots to fulfill the constraints while minimizing the beam-on time. The system is called IntuitivePlan and allows data to be transferred from generated dose plans into the Gamma Knife treatment planning software for further dosimetry evaluation.

RESULTS

The system has been very efficiently implemented, and an optimal plan is usually obtained in less than 1 to 2 minutes, depending on the complexity of the problem, on a desktop computer or in only a few minutes on a high-end laptop. Dosimetry data from 5 cases, 2 meningiomas and 3 vestibular schwannomas, were generated with IntuitivePlan. Results of evaluation of the dosimetry characteristics are very satisfactory and adequate in terms of conformity, selectivity, gradient, protection of organs at risk, and treatment time.

CONCLUSIONS

The possibility of using optimal, interactive real-time inverse planning in conjunction with the Leksell Gamma Knife opens new perspectives in radiosurgery, especially considering the potential use of the full capabilities of the latest generations of the Leksell Gamma Knife. This approach gives new users the possibility of using the system for easier and quicker access to good-quality plans with a shorter technical training period and opens avenues for new planning strategies for expert users. The use of a convex optimization approach allows an optimal plan to be provided in a very short processing time. This way, innovative graphical user interfaces can be developed, allowing the user to interact directly with the planning system to graphically define the desired dose map and to modify on-the-fly the dose map by moving, in a very user-friendly manner, the isodose surfaces of an initial plan. Further independent quantitative prospective evaluation comparing inverse planned and forward planned cases is warranted to validate this novel and promising treatment planning approach.

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Emrah Celtikci, Fatih Yakar, Pinar Celtikci and Yusuf Izci

OBJECTIVE

The aim of this study was to investigate the relationship between lumbar spondylolysis and payload weight between different combat units of Turkish land forces (TLF).

METHOD

The authors reviewed clinical and radiological data of the military personnel with low-back pain (LBP) admitted to their clinic between July 2017 and July 2018. Age, BMI, average payload weight, and military service unit were recorded. CT scans were evaluated for pars interarticularis fractures and spondylolisthesis, whereas MRI studies were evaluated for spondylolisthesis, Modic-type endplate changes, or signal loss on T2-weighted images compatible with disc degeneration.

RESULT

Following exclusion, a total of 642 all-male military personnel were included. Of these personnel, 122 were commandos, 435 were infantry, and 85 were serving in the artillery units. Bilateral pars interarticularis fracture was noted in 42 commandos (34.42%) and 2 infantrymen (0.45%). There was no spondylolysis in the artillery units. There was no multiple-level spondylolysis and the most common level of spondylolysis was L5. Commandos had a significantly higher incidence of spondylolysis and more average payload weight (p < 0.001). Twelve patients (27.2%) with spondylolysis had accompanying MRI pathologies at the same level, whereas 32 patients (72.7%) had no accompanying MRI pathologies.

CONCLUSIONS

Increased payload weight in military personnel is associated with spondylolysis, and commandos in the TLF have significantly heavier payloads, which causes an increased rate of spondylolysis compared to other units. Additionally, spondylolysis without adjacent-level changes on MRI could be undiagnosed. LBP in active military personnel who have a history of carrying heavy payloads should be evaluated extensively with both MRI and CT scans.

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Daniel B. Herrick, Joseph E. Tanenbaum, Marc Mankarious, Sagar Vallabh, Eitan Fleischman, Swamy Kurra, Shane M. Burke, Marie Roguski, Thomas E. Mroz, William F. Lavelle, Jeffrey E. Florman and Ron I. Riesenburger

OBJECTIVE

Use of surgical site drains following posterior cervical spine surgery is variable, and its impact on outcomes remains controversial. Studies of drain use in the lumbar spine have suggested that drains are not associated with reduction of reoperations for wound infection or hematoma. There is a paucity of studies examining this relationship in the cervical spine, where hematomas and infections can have severe consequences. This study aims to examine the relationship between surgical site drains and reoperation for wound-related complications following posterior cervical spine surgery.

METHODS

This study is a multicenter retrospective review of 1799 consecutive patients who underwent posterior cervical decompression with instrumentation at 4 tertiary care centers between 2004 and 2016. Demographic and perioperative data were analyzed for associations with drain placement and return to the operating room.

RESULTS

Of 1799 patients, 1180 (65.6%) had a drain placed. Multivariate logistic regression analysis identified history of diabetes (OR 1.37, p = 0.03) and total number of levels operated (OR 1.32, p < 0.001) as independent predictors of drain placement. Rates of reoperation for any surgical site complication were not different between the drain and no-drain groups (4.07% vs 3.88%, p = 0.85). Similarly, rates of reoperation for surgical site infection (1.61% vs 2.58%, p = 0.16) and hematoma (0.68% vs 0.48%, p = 0.62) were not different between the drain and no-drain groups. However, after adjusting for history of diabetes and the number of operative levels, patients with drains had significantly lower odds of returning to the operating room for surgical site infection (OR 0.48, p = 0.04) but not for hematoma (OR 1.22, p = 0.77).

CONCLUSIONS

This large study characterizes current practice patterns in the utilization of surgical site drains during posterior cervical decompression and instrumentation. Patients with drains placed did not have lower odds of returning to the operating room for postoperative hematoma. However, the authors’ data suggest that patients with drains may be less likely to return to the operating room for surgical site infection, although the absolute number of infections in the entire population was small, limiting the analysis.