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Lawrence S. Chin, Lijun Ma and Steven DiBiase

Object. Radiation necrosis is the only significant complication of gamma knife surgery (GKS). The authors studied treatment plan parameters in patients who had radiation necrosis to determine if risk factors for necrosis could be identified.

Methods. Between September 1994 and December 1998, 286 patients were treated with GKS by the senior author. Of the 243 patients who were suitable for analysis, 17 developed radiation necrosis and were prospectively followed. Concurrently, 17 patients without necrosis were randomly selected as case controls on the basis of histological findings in their lesions. Integral dose—volume histograms (DVHs) were calculated and dose—volume treatment parameters were determined. A comparison was made with both the established Kjellberg and Flickinger isonecrosis risk lines. Clinical outcome was assessed according to time to resolution of symptoms and return to normal radiographic appearance.

Conclusions. Treatment plan variables associated with the risk of necrosis were increased tumor volume (TV) integral dose, increased TV, and increased 10-Gy volume. Other risk factors included repeated radiosurgery to the same lesion and glioma histological findings. The Kjellberg 1% risk line predicted a 5% risk of radiation necrosis and the Flickinger 3% risk line predicted a 3% risk. The median time to development of necrosis was 4 months, and symptomatic and radiographic recovery times were 7.5 and 10.5 months, respectively. The median survival time in patients with necrosis was 30 months. The authors recommend prospective TV determination and DVH calculation for all radiosurgical treatments and the avoidance of repeated radiosurgical treatments to the same lesion when possible.

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Kang Guo, Lijun Heng, Haihong Zhang, Lei Ma, Hui Zhang and Dong Jia

OBJECTIVE

The authors sought to identify the relevance between pneumocephalus and postoperative intracranial infections, as well as bacteriological characteristics and risk factors for intracranial infections, in patients with pituitary adenomas after endoscopic endonasal transsphenoidal surgery.

METHODS

In total, data from 251 consecutive patients with pituitary adenomas who underwent pure endoscopic endonasal transsphenoidal surgeries from 2014 to 2018 were reviewed for preoperative comorbidities, intraoperative techniques, and postoperative care.

RESULTS

This retrospective study found 18 cases of postoperative pneumocephalus (7.17%), 9 CNS infections (3.59%), and 12 CSF leaks (4.78%). Of the patients with pneumocephalus, 5 (27.8%) had CNS infections. In patients with CNS infections, the culture results were positive in 7 cases and negative in 2 cases. The statistical analysis suggested that pneumocephalus (maximum bubble diameter of ≥ 1 cm), diaphragmatic defects (intraoperative CSF leak, Kelly grade ≥ 1), and a postoperative CSF leak are risk factors for postoperative CNS infections.

CONCLUSIONS

In pituitary adenoma patients who underwent pure endoscopic endonasal transsphenoidal surgeries, intraoperative saddle reconstruction has a crucial role for patients with postoperative intracranial infections. Additionally, postoperative pneumocephalus plays an important role in predicting intracranial infections that must not be neglected. Therefore, neurosurgeons should pay close attention to the discovery of postoperative intracranial pneumocephalus because this factor is as important as a postoperative CSF leak. Pneumocephalus (maximum bubble diameter of ≥ 1 cm), diaphragmatic defects (an intraoperative CSF leak, Kelly grade ≥ 1), and a postoperative CSF leak were risk factors predictive of postoperative intracranial infections. In addition, it is essential that operative procedures be carefully performed to avoid diaphragmatic defects, to reduce exposure to the external environment, and to decrease patients’ suffering.

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Peng Dong, Angélica Pérez-Andújar, Dilini Pinnaduwage, Steve Braunstein, Philip Theodosopoulos, Michael McDermott, Penny Sneed and Lijun Ma

OBJECTIVE

Noninvasive Gamma Knife (GK) platforms, such as the relocatable frame and on-board imaging, have enabled hypofractionated GK radiosurgery of large or complex brain lesions. This study aimed to characterize the dosimetric quality of such treatments against linear accelerator–based delivery systems that include the CyberKnife (CK) and volumetric modulated arc therapy (VMAT).

METHODS

Ten patients treated with VMAT at the authors' institution for large brain tumors (> 3 cm in maximum diameter) were selected for the study. The median prescription dose was 25 Gy (range 20–30 Gy) in 5 fractions. The median planning target volume (PTV) was 9.57 cm3 (range 1.94–24.81 cm3). Treatment planning was performed using Eclipse External Beam Planning V11 for VMAT on the Varian TrueBeam system, Multiplan V4.5 for the CyberKnife VSI System, and Leksell GammaPlan V10.2 for the Gamma Knife Perfexion system. The percentage of the PTV receiving at least the prescription dose was normalized to be identical across all platforms for individual cases. The prescription isodose value for the PTV, conformity index, Paddick gradient index, mean and maximum doses for organs at risk, and normal brain dose at variable isodose volumes ranging from the 5-Gy isodose volume (V5) to the 15-Gy isodose volume (V15) were compared for all of the cases.

RESULTS

The mean Paddick gradient index was 2.6 ± 0.2, 3.2 ± 0.5, and 4.3 ± 1.0 for GK, CK, and VMAT, respectively (p < 0.002). The mean V15 was 7.5 ± 3.7 cm3 (range 1.53–13.29 cm3), 9.8 ± 5.5 cm3 (range 2.07–18.45 cm3), and 16.1 ± 10.6 cm3 (range 3.58–36.53 cm3) for GK, CK, and VMAT, respectively (p ≤ 0.03, paired 2-tailed t-tests). However, the average conformity index was 1.18, 1.12, and 1.21 for GK, CK, and VMAT, respectively (p > 0.06). The average prescription isodose values were 52% (range 47%–69%), 60% (range 46%–68%), and 88% (range 70%–94%) for GK, CK, and VMAT, respectively, thus producing significant variations in dose hot spots among the 3 platforms. Furthermore, the mean V5 values for GK and CK were similar (p > 0.79) at 71.9 ± 36.2 cm3 and 73.3 ± 31.8 cm3, respectively, both of which were statistically lower (p < 0.01) than the mean V5 value of 124.6 ± 67.1 cm3 for VMAT.

CONCLUSIONS

Significantly better near-target normal brain sparing was noted for hypofractionated GK radiosurgery versus linear accelerator–based treatments. Such a result supports the use of a large number of isocenters or confocal beams for the benefit of normal tissue sparing in hypofractionated brain radiosurgery.

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Joshua Chiu, Steve Braunstein, Jean Nakamura, Philip Theodosopoulos, Penny Sneed, Michael McDermott and Lijun Ma

OBJECTIVE

Interfractional residual patient shifts are often observed during the delivery of hypofractionated brain radiosurgery. In this study, the authors developed a robustness treatment planning check procedure to assess the dosimetric effects of residual target shifts on hypofractionated Gamma Knife radiosurgery (GKRS).

METHODS

The residual patient shifts were determined during the simulation process immediately after patient immobilization. To mimic incorporation of residual target shifts during treatment delivery, a quality assurance procedure was developed to sample and shift individual shots according to the residual uncertainties in the prescribed treatment plan. This procedure was tested and demonstrated for 10 hypofractionated GKRS cases.

RESULTS

The maximum residual target shifts were less than 1 mm for the studied cases. When incorporating such shifts, the target coverage varied by 1.9% ± 2.2% (range 0.0%–7.1%) and selectivity varied by 3.6% ± 2.5% (range 1.1%–9.3%). Furthermore, when incorporating extra random shifts on the order of 0.5 mm, the target coverage decreased by as much as 7%, and nonisocentric variation in the dose distributions was noted for the studied cases.

CONCLUSIONS

A pretreatment robustness check procedure was developed and demonstrated for hypofractionated GKRS. Further studies are underway to implement this procedure to assess maximum tolerance levels for individual patient cases.

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Lijun Ma, Lynn Verhey, Cynthia Chuang, Martina Descovich, Vernon Smith, Kim Huang, Michael McDermott and Penny Sneed

Object

The new capability of composite sector collimation in Gamma Knife Perfexion produces complex, nonspherical, and nonelliptical dose distributions. In this study, the authors investigated the effect of composite sector collimation on average dose fall-off compared with the previous Gamma Knife model.

Methods

A general formalism was derived to describe the peripheral dose distribution of all Gamma Knife models in the form of (V/V0) = (D/D0)γ, where V is the volume of the peripheral isodose line with the value of D, V0 is the reference prescription isodose volume, D0 is the prescription dose, and γ is the fitting parameter that determines how fast the dose falls off near the target. Based on this formula, the authors compared 40 cases involving patients treated with Gamma Knife Perfexion with 40 similar cases involving patients treated with Gamma Knife model 4C. The cases were grouped based on the use of the sector collimators in the treatment planning process. For each group as well as all cases combined, the mean γ values were compared by means of the Student t-test for varying ranges of the peripheral dose distribution—from 100% of the prescription dose to 75, 50, and 25% of the prescription dose.

Results

The fit of general formula to the data was excellent for both Gamma Knife Perfexion and Gamma Knife 4C with R2> 0.99 for all the cases. The overall γ values (mean ± 2 standard deviations) were as follows: γ = −1.74 ± 0.47 (Model 4C) versus −1.77 ± 0.40 (Perfexion) within 100–75% of the prescription dose; γ = −1.57 ± 0.26 (Model 4C) versus −1.58 ± 0.25 (Perfexion) within 100–50% of the prescription dose; γ = −1.47 ± 0.18 (Model 4C) versus −1.50 ± 0.16 (Perfexion) within 100–25% of the prescription dose. No statistical significance between the mean differences for Gamma Knife Perfexion and Model 4C was found within these ranges. The probability values were 0.65, 0.84, and 0.22, respectively.

Conclusions

The use of composite sector collimators in Gamma Knife Perfexion demonstrated no statistically significant effects on the volume-averaged dose fall-off near a target periphery for typical treatment cases.

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Penny K. Sneed, Joe Mendez, Johanna G. M. Vemer-van den Hoek, Zachary A. Seymour, Lijun Ma, Annette M. Molinaro, Shannon E. Fogh, Jean L. Nakamura and Michael W. McDermott

OBJECT

The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases.

METHODS

All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed.

RESULTS

Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3–18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were < 1%, 1%, 3%, 10%, and 14% for maximum diameter 0.3–0.6 cm, 0.7–1.0 cm, 1.1–1.5 cm, 1.6–2.0 cm, and 2.1–5.1 cm, respectively. The 1-year probabilities of symptomatic ARE leveled off at 13%–14% for brain metastases maximum diameter > 2.1 cm, target volume > 1.2 cm3, prescription isodose volume > 1.8 cm3,12-Gy volume > 3.3 cm3, and 10-Gy volume > 4.3 cm3, excluding lesions treated with repeat SRS. On both univariate and multivariate analysis, capecitabine, but not other systemic therapy within 1 month of SRS, appeared to increase ARE risk. For the multivariate analysis considering only metastases with target volume > 1.0 cm3, risk factors for ARE included prior SRS, kidney primary tumor, connective tissue disorder, and capecitabine.

CONCLUSIONS

Although incidence of ARE after SRS was low overall, risk increased rapidly with size and volume, leveling off at a 1-year cumulative incidence of 13%–14%. This study describes the time course of ARE and provides risk estimates by various lesion characteristics and treatment parameters to aid in decision-making and patient counseling.

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Stereotactic radiosurgery for tremor: systematic review

International Stereotactic Radiosurgery Society practice guidelines

Nuria E. Martínez-Moreno, Arjun Sahgal, Antonio De Salles, Motohiro Hayashi, Marc Levivier, Lijun Ma, Ian Paddick, Jean Régis, Sam Ryu, Ben J. Slotman and Roberto Martínez-Álvarez

OBJECTIVE

The aim of this systematic review is to offer an objective summary of the published literature relating to stereotactic radiosurgery (SRS) for tremor and consensus guideline recommendations.

METHODS

This systematic review was performed up to December 2016. Article selection was performed by searching the MEDLINE (PubMed) and EMBASE electronic bibliographic databases. The following key words were used: “radiosurgery” and “tremor” or “Parkinson’s disease” or “multiple sclerosis” or “essential tremor” or “thalamotomy” or “pallidotomy.” The search strategy was not limited by study design but only included key words in the English language, so at least the abstract had to be in English.

RESULTS

A total of 34 full-text articles were included in the analysis. Three studies were prospective studies, 1 was a retrospective comparative study, and the remaining 30 were retrospective studies. The one retrospective comparative study evaluating deep brain stimulation (DBS), radiofrequency thermocoagulation (RFT), and SRS reported similar tremor control rates, more permanent complications after DBS and RFT, more recurrence after RFT, and a longer latency period to clinical response with SRS. Similar tremor reduction rates in most of the reports were observed with SRS thalamotomy (mean 88%). Clinical complications were rare and usually not permanent (range 0%–100%, mean 17%, median 2%). Follow-up in general was too short to confirm long-term results.

CONCLUSIONS

SRS to the unilateral thalamic ventral intermediate nucleus, with a dose of 130–150 Gy, is a well-tolerated and effective treatment for reducing medically refractory tremor, and one that is recommended by the International Stereotactic Radiosurgery Society.

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Stereotactic radiosurgery for trigeminal neuralgia: a systematic review

International Stereotactic Radiosurgery Society practice guidelines

Constantin Tuleasca, Jean Régis, Arjun Sahgal, Antonio De Salles, Motohiro Hayashi, Lijun Ma, Roberto Martínez-Álvarez, Ian Paddick, Samuel Ryu, Ben J. Slotman and Marc Levivier

OBJECTIVES

The aims of this systematic review are to provide an objective summary of the published literature specific to the treatment of classical trigeminal neuralgia with stereotactic radiosurgery (RS) and to develop consensus guideline recommendations for the use of RS, as endorsed by the International Society of Stereotactic Radiosurgery (ISRS).

METHODS

The authors performed a systematic review of the English-language literature from 1951 up to December 2015 using the Embase, PubMed, and MEDLINE databases. The following MeSH terms were used in a title and abstract screening: “radiosurgery” AND “trigeminal.” Of the 585 initial results obtained, the authors performed a full text screening of 185 studies and ultimately found 65 eligible studies. Guideline recommendations were based on level of evidence and level of consensus, the latter predefined as at least 85% agreement among the ISRS guideline committee members.

RESULTS

The results for 65 studies (6461 patients) are reported: 45 Gamma Knife RS (GKS) studies (5687 patients [88%]), 11 linear accelerator (LINAC) RS studies (511 patients [8%]), and 9 CyberKnife RS (CKR) studies (263 patients [4%]). With the exception of one prospective study, all studies were retrospective.

The mean maximal doses were 71.1–90.1 Gy (prescribed at the 100% isodose line) for GKS, 83.3 Gy for LINAC, and 64.3–80.5 Gy for CKR (the latter two prescribed at the 80% or 90% isodose lines, respectively). The ranges of maximal doses were as follows: 60–97 Gy for GKS, 50–90 Gy for LINAC, and 66–90 Gy for CKR.

Actuarial initial freedom from pain (FFP) without medication ranged from 28.6% to 100% (mean 53.1%, median 52.1%) for GKS, from 17.3% to 76% (mean 49.3%, median 43.2%) for LINAC, and from 40% to 72% (mean 56.3%, median 58%) for CKR. Specific to hypesthesia, the crude rates (all Barrow Neurological Institute Pain Intensity Scale scores included) ranged from 0% to 68.8% (mean 21.7%, median 19%) for GKS, from 11.4% to 49.7% (mean 27.6%, median 28.5%) for LINAC, and from 11.8% to 51.2% (mean 29.1%, median 18.7%) for CKR. Other complications included dysesthesias, paresthesias, dry eye, deafferentation pain, and keratitis. Hypesthesia and paresthesia occurred as complications only when the anterior retrogasserian portion of the trigeminal nerve was targeted, whereas the other listed complications occurred when the root entry zone was targeted. Recurrence rates ranged from 0% to 52.2% (mean 24.6%, median 23%) for GKS, from 19% to 63% (mean 32.2%, median 29%) for LINAC, and from 15.8% to 33% (mean 25.8%, median 27.2%) for CKR. Two GKS series reported 30% and 45.3% of patients who were pain free without medication at 10 years.

CONCLUSIONS

The literature is limited in its level of evidence, with only one comparative randomized trial (1 vs 2 isocenters) reported to date. At present, one can conclude that RS is a safe and effective therapy for drug-resistant trigeminal neuralgia. A number of consensus statements have been made and endorsed by the ISRS.

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Stereotactic body radiotherapy for de novo spinal metastases: systematic review

International Stereotactic Radiosurgery Society practice guidelines

Zain A. Husain, Arjun Sahgal, Antonio De Salles, Melissa Funaro, Janis Glover, Motohiro Hayashi, Masahiro Hiraoka, Marc Levivier, Lijun Ma, Roberto Martínez-Alvarez, J. Ian Paddick, Jean Régis, Ben J. Slotman and Samuel Ryu

OBJECTIVE

The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases.

METHODS

The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language.

RESULTS

A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16–24 Gy/1 fraction (fx), 24 Gy/2 fx, 24–27 Gy/3 fx, and 30–35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported.

CONCLUSION

There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.

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Reirradiation spine stereotactic body radiation therapy for spinal metastases: systematic review

International Stereotactic Radiosurgery Society practice guidelines

Sten Myrehaug, Arjun Sahgal, Motohiro Hayashi, Marc Levivier, Lijun Ma, Roberto Martinez, Ian Paddick, Jean Régis, Samuel Ryu, Ben Slotman and Antonio De Salles

OBJECTIVE

Spinal metastases that recur after conventional palliative radiotherapy have historically been difficult to manage due to concerns of spinal cord toxicity in the retreatment setting. Spine stereotactic body radiation therapy (SBRT), also known as stereotactic radiosurgery, is emerging as an effective and safe means of delivering ablative doses to these recurrent tumors. The authors performed a systematic review of the literature to determine the clinical efficacy and safety of spine SBRT specific to previously irradiated spinal metastases.

METHODS

A systematic literature review was conducted, which was specific to SBRT to the spine, using MEDLINE, Embase, Cochrane Evidence-Based Medicine Database, National Guideline Clearinghouse, and CMA Infobase, with further bibliographic review of appropriate articles. Research questions included: 1) Is retreatment spine SBRT efficacious with respect to local control and symptom control? 2) Is retreatment spine SBRT safe?

RESULTS

The initial literature search retrieved 2263 articles. Of these articles, 160 were potentially relevant, 105 were selected for in-depth review, and 9 studies met all inclusion criteria for analysis. All studies were single-institution series, including 4 retrospective, 3 retrospective series of prospective databases, 1 prospective, and 1 Phase I/II prospective study (low- or very low–quality data). The results indicated that spine SBRT is effective, with a median 1-year local control rate of 76% (range 66%–90%). Improvement in patients’ pain scores post-SBRT ranged from 65% to 81%. Treatment delivery was safe, with crude rates of vertebral body fracture of 12% (range 0%–22%) and radiation-induced myelopathy of 1.2%.

CONCLUSIONS

This systematic literature review suggests that SBRT to previously irradiated spinal metastases is safe and effective with respect to both local control and pain relief. Although the evidence is limited to low-quality data, SBRT can be a recommended treatment option for reirradiation.