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Ian Paddick

✓ A conformity index is a measure of how well the volume of a radiosurgical dose distribution conforms to the size and shape of a target volume. Because the success of radiosurgery is related to the extremely conformal irradiation of the target, an accurate method for describing this parameter is important. Existing conformity ratios and indices used in radiosurgery are reviewed and criticized. It will be demonstrated that previously proposed measurements of conformity can, under certain conditions, give false perfect scores. A new conformity index is derived that gives an objective score of conformity for a treatment plan and gives no false scores.

An analysis of five different treatment plans is made using both the existing scoring methods and the new conformity index.

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Ian Paddick and Bodo Lippitz

✓A dose gradient index (GI) is proposed that can be used to compare treatment plans of equal conformity. The steep dose gradient outside the radiosurgical target is one of the factors that makes radiosurgery possible. It therefore makes sense to measure this variable and to use it to compare rival plans, explore optimal prescription isodoses, or compare treatment modalities.

The GI is defined as the ratio of the volume of half the prescription isodose to the volume of the prescription isodose. For a plan normalized to the 50% isodose line, it is the ratio of the 25% isodose volume to that of the 50% isodose volume.

The GI will differentiate between plans of similar conformity, but with different dose gradients, for example, where isocenters have been inappropriately centered on the edge of the target volume.

In a retrospective series of 50 dose plans for the treatment of vestibular schwannoma, the optimal prescription isodose was assessed. A mean value of 40% (median 38%, range 30–61%) was calculated, not 50% as might be anticipated. The GI can show which of these prescription isodoses will give the steepest dose falloff outside the target.

When planning a multiisocenter treatment, there may be a temptation to place some isocenters on the edge of the target. This has the apparent advantage of producing a plan of good conformity and a predictable prescription isodose; however, it risks creating a plan that has a low dose gradient outside the target. The quality of this dose gradient is quantified by the GI.

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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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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.

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Caroline Chung, Dheerendra Prasad, Michael Torrens, Ian Paddick, Patrick Hanssens, Douglas Kondziolka and David A. Jaffray

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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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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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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 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.