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Chung Ping Yu, Joel Yiu Chung Cheung, Samuel Leung and Robert Ho

Object. The purpose of this study was to confirm, by using a sequential volume mapping (SVM) technique, that gamma knife radiosurgery (GKS) induces negative growth in vestibular schwannomas (VS).

Methods. Over a period of 5 years, 126 small- to medium-sized (< 15 cm3) VSs were treated using microradiosurgical techniques within a standard protocol. All patient data were collected prospectively. Sequential magnetic resonance imaging was performed every 6 months to assess the volume of the tumor, based on specially developed GammaPlan software. The mean follow-up duration was 22 months. At least three SVM measurements were obtained in 91 patients and at least four were obtained in 62 patients. The mean number of SVM measurements for each patient was 2.54. After GKS, the following patterns of volume change were seen: 1) 57 VSs showed transient increase in volume with a peak at 6 months, followed by shrinkage. Four VSs exhibited prolonged swelling beyond 24 months. Transient swelling and eventual shrinkage were independent of the initial VS volume; 2) 29 VSs showed direct volume shri6nkage without swelling; and 3) five VSs showed persistent volume increase. All volume changes were greater than 10%. The overall mean volume reduction was 46.8% at 30 months.

Conclusions. Sequential volume mapping appears to be superior to conventional two-dimensional measurements in monitoring volume changes in VS after GKS. It confirms that transient swelling is common. Ninety-two percent of tumors responded by showing significant volume shrinkage (mean 46.8%). It would seem that GKS can induce volume reduction in VS.

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Lai-fung Li, Chung-ping Yu, Anderson Chun-on Tsang, Benedict Beng-teck Taw and Wai-man Lui

Gamma Knife radiosurgery (GKRS) is a frequent treatment choice for patients with small- to moderate-sized vestibular schwannoma (VS). However, pseudoprogression after GKRS is commonly observed, with a reported incidence ranging from 7% to 77%. The wide range of the reported incidence of pseudoprogression reflects the fact that there is no consensus on how it should be diagnosed.

The authors present the case of a 66-year-old woman who had a 2.5-cm right-sided VS treated with GKRS in 1997. The first posttreatment MRI obtained 5 months later showed that the tumor volume had increased to 9.7 cm3. The tumor volume increased further and reached its peak 24 months after treatment at 20.9 cm3, which was a 161% increase from pretreatment volume. Thereafter, the tumor shrank gradually and mass effect on the brainstem reduced over time. By 229 months after treatment, the tumor volume was 1.0 cm3, equaling 12.5% of pretreatment tumor volume, or 4.8% of peak tumor volume after treatment. This case demonstrates that if a patient remains asymptomatic despite a dramatic increase in tumor volume after GKRS, observation remains an option, because even a very sizable tumor can shrink with near-complete resolution. Patients undergoing GKRS for VS should be counseled regarding the possibility of pseudoprogression, and followed carefully over time while avoiding premature decisions for surgical removal after treatment.

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Michael Torrens, Caroline Chung, Hyun-Tai Chung, Patrick Hanssens, David Jaffray, Andras Kemeny, David Larson, Marc Levivier, Christer Lindquist, Bodo Lippitz, Josef Novotny Jr., Ian Paddick, Dheerendra Prasad and Chung Ping Yu

Object

This report has been prepared to ensure more uniform reporting of Gamma Knife radiosurgery treatment parameters by identifying areas of controversy, confusion, or imprecision in terminology and recommending standards.

Methods

Several working group discussions supplemented by clarification via email allowed the elaboration of a series of provisional recommendations. These were also discussed in open session at the 16th International Leksell Gamma Knife Society Meeting in Sydney, Australia, in March 2012 and approved subject to certain revisions and the performance of an Internet vote for approval from the whole Society. This ballot was undertaken in September 2012.

Results

The recommendations in relation to volumes are that Gross Target Volume (GTV) should replace Target Volume (TV); Prescription Isodose Volume (PIV) should generally be used; the term Treated Target Volume (TTV) should replace TVPIV, GTV in PIV, and so forth; and the Volume of Accepted Tolerance Dose (VATD) should be used in place of irradiated volume. For dose prescription and measurement, the prescription dose should be supplemented by the Absorbed Dose, or DV% (for example, D95%), the maximum and minimum dose should be related to a specific tissue volume (for example, D2% or preferably D1 mm3), and the median dose (D50%) should be recorded routinely. The Integral Dose becomes the Total Absorbed Energy (TAE). In the assessment of planning quality, the use of the Target Coverage Ratio (TTV/ GTV), Paddick Conformity Index (PCI = TTV2/[GTV · PIV]), New Conformity Index (NCI = [GTV · PIV]/TTV2), Selectivity Index (TTV/PIV), Homogeneity Index (HI = [D2% –D98%]/D50%), and Gradient Index (GI = PIV0.5/PIV) are reemphasized. In relation to the dose to Organs at Risk (OARs), the emphasis is on dose volume recording of the VATD or the dose/volume limit (for example, V10) in most cases, with the additional use of a Maximum Dose to a small volume (such as 1 mm3) and/or a Point Dose and Mean Point Dose in certain circumstances, particularly when referring to serial organs. The recommendations were accepted by the International Leksell Gamma Knife Society by a vote of 92% to 8%.

Conclusions

An agreed-upon and uniform terminology and subsequent standardization of certain methods and procedures will advance the clinical science of stereotactic radiosurgery.

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Tak Lap Poon, Samuel Cheong Lun Leung, Christopher Yee Fat Poon and Chung Ping Yu

Object

Gamma Knife surgery (GKS) is gaining popularity in the treatment of patients with acromegaly after transsphenoidal tumor excision. In this paper, the authors examine the efficacy of GKS and predictors for biochemical remission.

Methods

The authors retrospectively reviewed data spanning the period 1997–2008 in their hospital Gamma Knife statistics database. Forty patients with a mean age of 64 years (range 19–73 years) underwent GKS for acromegaly during that period. Transsphenoidal subtotal tumor excision had been performed prior to GKS in all these patients, except for 3 deemed to be at high surgical risk. All GKS treatment plans were formulated by the same team that performed the microsurgical procedures. Biochemical remission was defined as a growth hormone (GH) level < 2 ng/ml and an insulin-like growth factor–I level that was considered normal with reference to the patient's age and sex. The mean follow-up period after radiosurgery was 73.8 months (range 12–132 months).

Results

Three patients died during the study period of causes unrelated to surgery or GKS. Twenty-nine patients (72.5%) underwent 1 radiosurgery session, and 11 patients (27.5%) required 2 radiosurgery sessions. Among the patients who underwent 1 radiosurgery session, excellent responses (76%–100% reductions in tumor size, GH level, and insulin-like growth factor–I level) were observed in 18 (62%; p < 0.0001), 20 (69%; p < 0.0001), and 5 patients (17%; p = 0.21), respectively. Tumors < 1 cm3 and those with no evidence of cavernous sinus extension were statistically significantly related to a good response in tumor size reduction (p = 0.029 and p = 0.0016, respectively). Subgroup analyses were performed in patients who attained biochemical remission in GH levels; the subgroups included patient sex, patient age, target volume, isodose volume, prescribed dose and isodose, pre-GKS GH level, and evidence of cavernous sinus extension. Only male sex was found to be a statistically significant predictor of good hormone regulation (p = 0.0124). The presence of a cavernous sinus extension was the statistically significant predictor of poor hormone control (p = 0.0011) in our study.

Conclusions

Subtotal tumor excision followed by GKS was an effective treatment for acromegaly. Tumors < 1 cm3 and those with no evidence of cavernous sinus extension responded well to treatment. Male sex and absence of cavernous sinus involvement can be regarded as predictors of biochemical remission.

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Motohiro Hayashi, Takaomi Taira, Mikhail Chernov, Seiji Fukuoka, Roman Liscak, Chung Ping Yu, Robert T. K. Ho, Jean Regis, Yoko Katayama, Yoriko Kawakami and Tomokatsu Hori

Object. The authors have treated intractable pain, particularly cancer pain related to bone metastasis, with various protocols. Cancer pain has been treated by gamma knife radiosurgery (GKS), targeted to the pituitary gland—stalk, as an alternative new pain control method. The purpose of this study was to investigate a prospective multicenter protocol to prove the efficacy and the safety of this treatment.

Methods. Indications for patient inclusion in this treatment protocol were: 1) pain related to bone metastasis; 2) no other effective pain treatment options; 3) general condition rated as greater than 40 on the Karnofsky Performance Scale; 4) morphine effective for pain control; and 5) no previous treatment with radiation (GKS or conventional radiotherapy) for brain metastasis. The authors at one institution have treated two patients, who suffered from severe cancer pain related to bone metastasis, by using GKS. The target was the pituitary gland. The maximum dose was 160 Gy with one isocenter of an 8-mm collimator, keeping the radiation dose to the optic nerve less than 8 Gy. At another institution two patients were treated in the same way; an additional five patients were treated similarly with targeting of the pituitary gland with two isocenters of 4-mm collimator.

In all nine cases, pain resolved without significant complication. Pain relief was observed within several days, and this effect was prolonged until the day that they died. At a follow up of 1 to 24 months, no recurrences and no hormonal dysfunction were observed.

Conclusions. Despite insufficient experience, the efficacy and the safety of GKS for intractable pain were demonstrated in nine patients. This treatment has the potential to ameliorate cancer-related pain, and GKS will play a more important role in the treatment of intractable pain. More experience and additional refined study protocols are needed to evaluate which parameters are important, to determine what treatment strategy is the best, and to clarify the safest option for patients with intractable cancer pain.