Leksell Top 25 - Since 2005

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Donald N. Liew, Hideyuki Kano, Douglas Kondziolka, David Mathieu, Ajay Niranjan, John C. Flickinger, John M. Kirkwood, Ahmad Tarhini, Stergios Moschos and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control.

Methods

The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm3 to 37.2 cm3. The median marginal dose was 18 Gy.

Results

Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months).

Conclusions

Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.

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Hideyuki Kano, Douglas Kondziolka, Aftab Khan, John C. Flickinger and L. Dade Lunsford

Object

Many patients with acoustic neuromas (ANs) have hearing function at diagnosis and desire to maintain it. To date, radiosurgical techniques have been focused on conformal irradiation of the tumor mass, with less attention to inner ear structures for which there was scant radiobiological information. The authors of this study evaluated tumor control and hearing preservation as they relate to tumor volume, imaging characteristics, and nerve and cochlear radiation dose following stereotactic radiosurgery (SRS) using the Gamma Knife.

Methods

Seventy-seven patients with ANs had serviceable hearing (Gardner-Robertson [GR] Class I or II) and underwent SRS between 2004 and 2007. This interval reflected more recent measurements of inner ear dosimetry during the authors' 21-year experience. The median patient age was 52 years (range 22–82 years). No patient had undergone any prior treatment for the ANs. The median tumor volume was 0.75 cm3 (range 0.07–7.7 cm3), and the median radiation dose to the tumor margin was 12.5 Gy (range 12–13 Gy). At diagnosis, a greater distance from the lateral tumor to the end of the internal auditory canal correlated with better hearing function.

Results

At a median of 20 months after SRS, no patient required any other additional treatment. Serviceable hearing was preserved in 71% of all patients and in 89% (46 patients) of those with GR Class I hearing. Significant prognostic factors for maintaining the same GR class included (all pre-SRS) GR Class I hearing, a speech discrimination score (SDS) ≥ 80%, a pure tone average (PTA) < 20 dB, and a patient age < 60 years. Significant prognostic factors for serviceable hearing preservation were (all pre-SRS) GR Class I hearing, an SDS ≥ 80%, a PTA < 20 dB, a patient age < 60 years, an intracanalicular tumor location, and a tumor volume < 0.75 cm3. Patients who received a radiation dose of < 4.2 Gy to the central cochlea had significantly better hearing preservation of the same GR class. Twelve of 12 patients < 60 years of age who had received a cochlear dose < 4.2 Gy retained serviceable hearing at 2 years post-SRS.

Conclusions

As currently practiced, SRS with the Gamma Knife preserves serviceable hearing in the majority of patients. Tumor volume and anatomy relate to the hearing level before radiosurgery and influence technique. A low radiosurgical dose to the cochlea enhances hearing preservation.

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Jay Jagannathan, Chun-Po Yen, Dibyendu Kumar Ray, David Schlesinger, Rod J. Oskouian, Nader Pouratian, Mark E. Shaffrey, James Larner and Jason P. Sheehan

Object

This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis.

Methods

A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2–115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75–35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery.

Results

The mean radiographic follow-up duration was 14 months (median 10 months, range 4–37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p = 0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p = 0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40–100).

Conclusion:

Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

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Toshinori Hasegawa, Dai Ishii, Yoshihisa Kida, Masayuki Yoshimoto, Joji Koike and Hiroshi Iizuka

Object

The purpose of this study was to evaluate radiosurgical outcomes in skull base chordomas and chondrosarcomas, and to determine which tumors are appropriate for stereotactic radiosurgery as adjuvant therapy following maximum tumor resection.

Methods

Thirty-seven patients (48 lesions) were treated using Gamma Knife surgery (GKS); 27 had chordomas, seven had chondrosarcomas, and three had radiologically diagnosed chordomas. The mean tumor volume was 20 ml, and the mean maximum and marginal doses were 28 and 14 Gy, respectively. The mean follow-up period was 97 months from diagnosis and 59 months from GKS.

Results

The actuarial 5- and 10-year survival rates after GKS were 80 and 53%, respectively. The actuarial 5- and 10-year local tumor control (LTC) rates after single or multiple GKS sessions were 76 and 67%, respectively. All patients with low-grade chondrosarcomas achieved good LTC. A tumor volume of less than 20 ml significantly affected the high rate of LTC (p = 0.0182). No patient had adverse radiation effects, other than one in whom facial numbness worsened despite successful tumor control.

Conclusions

As an adjuvant treatment after resection, GKS is a reasonable option for selected patients harboring skull base chordomas or chondrosarcomas with a residual tumor volume of less than 20 ml. Dose planning with a generous treatment volume to avoid marginal treatment failure should be made at a marginal dose of at least 15 Gy to achieve long-term tumor control.

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Juan J. Martin, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger, Karl A. Lozanne and L. Dade Lunsford

Object

Chordomas and chondrosarcomas of the skull base are aggressive and locally destructive tumors with a high tendency for local progression despite treatment. The authors evaluated the effect of stereotactic radiosurgery (SRS) on local tumor control and survival.

Methods

Twenty-eight patients with histologically confirmed chordomas (18) or chondrosarcomas (10) underwent Gamma Knife SRS either as primary or adjuvant treatment. Their ages ranged from 17 to 72 years (median 44 years). The most common presenting symptom was diplopia (26 patients, 93%). In two patients, SRS was the sole treatment. Twenty-six patients underwent between one and five additional surgical procedures. Two underwent an initial trans-sphenoidal biopsy. The average tumor volume was 9.8 cm3. The median dose to the tumor margin was 16 Gy.

Results

No patient was lost to follow-up. Transient symptomatic adverse radiation effects developed in only one patient. The actuarial local tumor control for chondrosarcomas at 5 years was 80 ± 10.1%. For chordomas both the actuarial tumor control and survival was 62.9 ± 10.4%.

Conclusions

Stereotactic radiosurgery is an important option for skull base chordomas and chondrosarcomas either as primary or adjunctive treatment. Multimodal management appears crucial to improve tumor control in most patients.

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Aurelia Kollová, Roman Liščák, Josef Novotný Jr., Vilibald Vladyka, Gabriela Šimonová and Ladislava Janoušková

Object

Meningioma is the most frequent benign tumor treated with Gamma Knife surgery (GKS); however, the assessment of its efficacy and safety in slow-growing tumors is an ongoing process, requiring analysis of long-term results.

Methods

Three hundred sixty-eight patients harboring 400 meningiomas treated between 1992 and 1999 at Na Homolce Hospital were evaluated. The median patient age was 57 years (range 18–84 years). The median tumor volume was 4.4 cm3 (range 0.11–44.9 cm3). The median tumor margin dose to the 50% isodose line was 12.55 Gy (range 6.5–24 Gy). Descriptive analysis was performed in 331 patients (90%); 325 patients had a follow-up longer than 24 months (median 60 months), and six patients were included because of posttreatment complications. The volume of treated tumors decreased in 248 cases (69.7%), remained the same in 99 (27.8%), and increased in nine (2.5%). The actuarial tumor control rate was 97.9% at 5 years post-GKS. Perilesional edema after radiosurgery was confirmed on neuroim-aging in 51 patients (15.4%). The temporary and permanent morbidity rates after radiosurgery were 10.2 and 5.7%, respectively.

Results

A significantly higher incidence of tumor volume increase was observed in men compared with women and in tumors treated with a margin dose lower than 12 Gy. Significant risk factors for edema included an age greater than 60 years, no previous surgery, perilesional edema before radiosurgery, a tumor volume greater than 10 cm3, a tumor location in the anterior fossa, and a margin dose greater than 16 Gy.

Conclusions

Stereotactic radiosurgery is a safe method of treatment for meningiomas. A minimum margin dose of 12 to 16 Gy seems to represent the therapeutic window for benign meningiomas with a high tumor control rate in a mid-term follow-up period.

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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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John W. Snell, Jason Sheehan, Matei Stroila and Ladislau Steiner

✓ The Gamma Knife has played an increasingly important role in the neurosurgical treatment of patients. Intracranial lesions are not removed by radiosurgery. Rather, the goal of treatment is to induce tumor control. During planning, the creation of dose–volume histograms requires an accurate volumetric analysis of intracranial lesions selected for radiosurgery. In addition, an accurate follow-up imaging analysis of tumor volume is essential for assessing the results of radiosurgery. Nevertheless, sources of volumetric error and their expected magnitudes must be properly understood so that the operator may correctly interpret apparent changes in tumor volume. In this paper, the authors examine the often-neglected contributions of imaging geometry (principally image slice thickness and separation) to overall volumetric error.

One of the fundamental sources of volumetric error is that resulting from the geometry of the acquisition protocol. The authors consider the image sampling geometry of tomographic modalities and its contribution to volumetric error through a simulation framework in which a synthetic digital tumor is taken as the primary model. Because the exact volume of the digital phantom can be computed, the volume estimates derived from tomographic “slicing” can be directly compared precisely and independently from other error sources. In addition to providing empirical bounds on volumetric error, this approach provides a tool for guiding the specification of imaging protocols when a specific volumetric accuracy, or volume change sensitivity, for particular structures is sought a priori.

Using computational geometry techniques, the volumetric error associated with image acquisition geometry was shown to be dependent on the number of slices through the region of interest (ROI) and the lesion volume. With a minimum of five slices through the ROI, the volume of a compact lesion could be calculated accurately with less than 10% error, which was the predetermined goal for the purposes of computing accurate dose–volume histograms and determining follow-up changes in tumor volume.

Accurate dose–volume histograms can be generated and follow-up volumetric assessments performed, assuming accurate lesion delineation, when the object is visualized on at least five axial slices. Volumetric analysis based on fewer than five slices yields unacceptably larger errors (that is, > 10%). These volumetric findings are particularly relevant for radiosurgical treatment planning and follow-up analysis. Through the application of this volumetric methodology and a greater understanding of the error associated with it, neurosurgeons can better perform radiosurgery and assess its outcome.