Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases

2009 ◽  
Vol 111 (3) ◽  
pp. 431-438 ◽  
Author(s):  
Jay Jagannathan ◽  
Chun-Po Yen ◽  
Dibyendu Kumar Ray ◽  
David Schlesinger ◽  
Rod J. Oskouian ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Local Tumor Control ◽  
Gross Total Resection ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Total Resection ◽  
Resection Cavity ◽  
The Mean ◽  
Performance Scale

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.

Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas

Neurosurgery ◽  
2015 ◽  
Vol 79 (1) ◽  
pp. 58-68 ◽  
Author(s):  
Or Cohen-Inbar ◽  
Cheng-chia Lee ◽  
David Schlesinger ◽  
Zhiyuan Xu ◽  
Jason P. Sheehan
Keyword(s):  
Skull Base ◽  
Tumor Volume ◽  
World Health ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Health Organization ◽  
Skull Base Meningiomas ◽  
Performance Scale

Abstract BACKGROUND: Gamma knife radiosurgery (GKRS) is well established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short intermediate period after radiosurgery. Reports of long-term tumor control and neurological status are still lacking. OBJECTIVE: To report the presentation, treatment, and long-term outcome of skull base meningiomas after GKRS. METHODS: From a prospectively collected institutional review board-approved database, we selected patients with a World Health Organization grade I skull base meningioma treated with a single-session GKRS and a minimum of 60 months follow-up. One hundred thirty-five patients, 54.1% males (n = 73), form the cohort. Median age was 54 years (19–80). Median tumor volume was 4.7 cm3 (0.5–23). Median margin dose was 15 Gy (7.5–36). Median follow-up was 102.5 months (60.1–235.4). Patient and tumor characteristics were assessed to determine the predictors of neurological function and tumor progression. RESULTS: At last follow-up, tumor volume control was achieved in 88.1% (n = 119). Post-GKRS clinical improvement or stability was reported in 61.5%. The 5-, 10-, and 15-year actuarial progression-free survival rates were 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor control and clinical preservation/improvement) was attained in 60.8% (n = 79). Pre-GKRS performance status (Karnofsky Performance Scale) was shown to influence tumor progression (P = .001) and post-GKRS clinical improvement/preservation (P = .003). CONCLUSION: GKRS offers a highly durable rate of tumor control for World Health Organization grade I skull base meningiomas, with an acceptably low incidence of neurological deficits. The Karnofsky Performance Scale at the time of radiosurgery serves as a reliable long-term predictor of overall outcome.

Long-term outcome of Gamma Knife stereotactic radiosurgery for arteriovenous malformations graded by the Spetzler-Martin classification

2013 ◽  
Vol 118 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Michael T. Koltz ◽  
Adam J. Polifka ◽  
Andreas Saltos ◽  
Robert G. Slawson ◽  
Young Kwok ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Arteriovenous Malformations ◽  
Lesion Size ◽  
Karnofsky Performance Scale ◽  
The Mean ◽  
Gamma Knife Stereotactic Radiosurgery ◽  
Karnofsky Performance Scale Score ◽  
Performance Scale

Object The object of this study was to assess outcomes in patients with arteriovenous malformations (AVMs) treated by Gamma Knife stereotactic radiosurgery (SRS); lesions were stratified by size, symptomatology, and Spetzler-Martin (S-M) grade. Methods The authors performed a retrospective analysis of 102 patients treated for an AVM with single-dose or staged-dose SRS between 1993 and 2004. Lesions were grouped by S-M grade, as hemorrhagic or nonhemorrhagic, and as small (< 3 cm) or large (≥ 3 cm). Outcomes included death, morbidity (new neurological deficit, new-onset seizure, or hemorrhage/rehemorrhage), nidus obliteration, and Karnofsky Performance Scale score. Results The mean follow-up was 8.5 years (range 5–16 years). Overall nidus obliteration (achieved in 75% of patients) and morbidity (19%) correlated with lesion size and S-M grade. For S-M Grade I–III AVMs, nonhemorrhagic and hemorrhagic combined, treatment yielded obliteration rates of 100%, 89%, and 86%, respectively; high functional status (Karnofsky Performance Scale Score ≥ 80); and 1% mortality. For S-M Grade IV and V AVMs, outcomes were less favorable, with obliteration rates of 54% and 0%, respectively. The AVMs that were not obliterated had a mean reduction in nidus volume of 69% (range 35%–96%). On long-term follow-up, 10% of patients experienced hemorrhage/rehemorrhage (6% mortality rate), which correlated with lesion size and S-M grade; the mean interval to hemorrhage was 81 months. Conclusions For patients with S-M Grade I–III AVMs, SRS offers outcomes that are favorable and that, except for the timing of obliteration, appear to be comparable to surgical outcomes reported for the same S-M grades. Staged-dose SRS results in lesion obliteration in half of patients with S-M Grade IV lesions.

scholarly journals The Role of a Navigational Radiofrequency Ablation Device and Concurrent Vertebral Augmentation for Treatment of Difficult-to-Reach Spinal Metastases

2021 ◽  
Vol 28 (5) ◽  
pp. 4004-4015
Author(s):  
Claudio Pusceddu ◽  
Davide De Francesco ◽  
Luca Melis ◽  
Nicola Ballicu ◽  
Alessandro Fancellu
Keyword(s):  
Radiofrequency Ablation ◽  
Pain Relief ◽  
Spinal Metastases ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Vertebral Augmentation ◽  
Local Tumor ◽  
Metastatic Lesions ◽  
The Mean

Aims: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control. Materials and Methods: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (>2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control. Results: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9–6.5) before tRFA and to 0.9 (95% CI 0.4–1.3) after tRFA (p < 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2–5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1–2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4–46 months) and 10 months (4–37 months), respectively. Conclusion: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases.

Embolization of Spinal Cord Arteriovenous Shunts: Morphological and Clinical Follow-up and Results—Review of 69 Consecutive Cases

Neurosurgery ◽  
2003 ◽  
Vol 53 (1) ◽  
pp. 40-50 ◽  
Author(s):  
Georges Rodesch ◽  
Michel Hurth ◽  
Beatrice Ducot ◽  
Hortensia Alvarez ◽  
Philippe David ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Endovascular Treatment ◽  
Scale Score ◽  
Karnofsky Performance Scale ◽  
Arteriovenous Shunts ◽  
The Mean ◽  
Acrylic Glue ◽  
Karnofsky Performance Scale Score ◽  
Performance Scale

Abstract OBJECTIVE We sought to analyze the results of embolization in patients with intradural spinal cord arteriovenous shunts. METHODS The clinical and radiological files of 69 of a population of 155 patients treated with embolization between 1981 and 1999 were reviewed retrospectively. The patients' clinical status was evaluated according to Karnofsky Performance Scale score. Twenty-one (14%) of 155 patients were treated surgically because they were thought to be poor candidates for embolization. Twenty-four (15%) of 155 patients were considered untreatable with surgery or embolization; in these patients, follow-up was proposed, but only 8 of them were followed appropriately and remained stable after the first consultation. Forty-one (26%) of 155 patients consulted our group, but no follow-up could be obtained. In 69 (45%) of 155 patients, comprising 20 children and 49 adults, endovascular treatment was performed with the patients under general anesthesia and without provocative tests, mainly with acrylic glue, in 99% of these patients. RESULTS The mean number of diagnostic and therapeutic sessions was 3.5 per patient, and the mean number of pure therapeutic sessions was 1.5 per patient. Follow-up ranged between 6 months and 18 years (mean, 5.6 yr). In 16% of patients, anatomic obliteration of spinal cord arteriovenous shunts was obtained. Embolization reduced more than 50% of the spinal cord arteriovenous shunts in 86% of cases. No recanalization was noted on follow-up angiograms. Good clinical outcomes were obtained in 83% of the patients: 15% of them were asymptomatic, 43% were improved, and 25% were stable. In 4% of patients, embolization failed to stabilize the disease. Transient deficits were seen after embolization in 14% of the patients, and permanent severe complications occurred in 4% of the patients (Karnofsky Performance Scale score ≤70). Mild worsening was seen in 9% of the patients (Karnofsky Performance Scale score, 80). No bleeding or rebleeding was seen after endovascular treatment was considered to have been completed. CONCLUSION This study proves that embolization with acrylic glue is a therapeutic option that compares favorably with surgery or embolization with other agents (particles, coils, or balloons). It offers stable long-term clinical results, despite not necessarily achieving total cure. Studies of larger series with longer follow-up are necessary to confirm these encouraging therapeutic data.

Relative roles of microsurgery and stereotactic radiosurgery for the treatment of patients with cranial meningiomas: a single-surgeon 4-year integrated experience with both modalities

2005 ◽  
Vol 102 ◽  
pp. 59-70 ◽  
Author(s):  
Mark E. Linskey ◽  
Stephen A. Davis ◽  
Vaneerat Ratanatharathorn
Keyword(s):  
Tumor Location ◽  
Conformity Index ◽  
Tumor Control ◽  
Karnofsky Performance Scale ◽  
Content Type ◽  
Treatment Groups ◽  
Simpson Grade ◽  
The Mean ◽  
Fine Print

Object.The authors sought to assess the respective roles of microsurgery and gamma knife surgery (GKS) in the treatment of patients with meningiomas.Methods.The authors culled from a 4-year prospective database data on 74 cases of meningiomas. Thirty-eight were treated with GKS and 35 with microsurgery. Simpson Grade 1 or 2 resection was achieved in 86.1% of patients who underwent microsurgery. Patients who underwent GKS received a mean margin dose of 16.4 Gy (range 14–20 Gy). The mean tumor coverage was 94.7%, and the mean conformity index was 1.76. Significant differences between the two treatment groups (GKS compared with microsurgery) included age (mean 60 compared with 50.7 years), volume (mean 7.85 cm3compared with 44.4 cm3), treatment history (55.3% compared with 14.3%), and tumor location (cavernous sinus/petroclival, 14 compared with three). The median follow up was 21.5 months (range 1.5–50 months). In patients with benign meningiomas GKS tumor control was 96.8% with one recurrence at the margin. The recurrence rate was zero of 27 for Simpson Grade 1 or 2 resection and three of four for higher grades in those patients who underwent microsurgery. There was no procedure-related mortality or permanent major neurological morbidity. The mean Karnofsky Performance Scale score was maintained for both forms of treatment. Symptoms improved in 48.4% of patients undergoing microsurgery and 16.7% of those who underwent GKS. Transient and permanent cranial nerve morbidity was 7.9 compared with 2.9%, and 5.3 compared with 8.5% for GKS and microsurgery, respectively. In a patient satisfaction survey 93.1% of microsurgery patients and 91.2% of GKS patients were highly satisfied.Conclusions.Both GKS and microsurgery serve important roles in the overall management of patients with meningiomas. Both are safe and effective and provide high degrees of satisfaction when used for differentially selected patients.

Results after treatment of craniopharyngiomas: further experiences with 73 patients since 1997

2012 ◽  
Vol 116 (2) ◽  
pp. 373-384 ◽  
Author(s):  
Bernd M. Hofmann ◽  
Anke Höllig ◽  
Christian Strauss ◽  
Rolf Buslei ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Neuropsychological Testing ◽  
Gross Total Resection ◽  
Moderate Increase ◽  
Total Resection ◽  
Cyst Aspiration ◽  
Transcranial Approach ◽  
The Mean ◽  
Subfrontal Approach ◽  
Previous Series

Object The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature. Methods A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months. Results Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors' former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%–66.7% vs 2.6%–50.0%) but were less frequent after transsphenoidal approaches (5.2%–19.2% vs 2.9%–45.7%). Conclusions Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients' condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.

Surgical Technique and Outcomes in the Treatment of Spinal Cord Ependymomas, Part 1: Intramedullary Ependymomas

2011 ◽  
Vol 68 (suppl_1) ◽  
pp. ons57-ons63 ◽  
Author(s):  
Elisa J Kucia ◽  
Nicholas C Bambakidis ◽  
Steve W Chang ◽  
Robert F Spetzler
Keyword(s):  
Spinal Cord ◽  
Radiation Therapy ◽  
Surgical Resection ◽  
Complication Rate ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Total Resection ◽  
Tertiary Center ◽  
The Mean

Abstract BACKGROUND: Intramedullary spinal ependymomas are rare tumors. OBJECTIVE: To provide a large retrospective review in the modern neuroimaging era from a tertiary center where aggressive surgical resection is favored. METHODS: Charts of intramedullary spinal ependymomas treated between 1983 and 2006 were reviewed. RESULTS: Sixty-seven cases were reviewed. The mean age was 45.6 years (range, 11-78 years) with a male-to-female ratio of 2:1. The most common location was the cervical spine, followed by the thoracic and lumbar spine. The average duration of symptoms was 33 months, with the most common symptom being pain and/or dysesthesias, followed by weakness, numbness, and urinary or sexual symptoms. Gross total resection was achieved in 55 patients and a subtotal resection was performed in 12 patients; 9 patients were treated with adjuvant radiation therapy. Mean follow-up was 32 months. The mean McCormick neurological grade at last follow-up was 2.0. The preoperative outcome correlated significantly with postoperative outcome (P &lt; .001). A significant number of patients who initially worsened improved at their 3-month follow-up examination. Outcomes were significantly worse in patients undergoing subtotal resection with or without radiation therapy (P &lt; .05). There were 3 recurrences. The overall complication rate was 34%. The primary complications were wound infections or cerebrospinal fluid leaks. CONCLUSION: Spinal cord ependymomas are difficult lesions to treat. Aggressive surgical resection is associated with a high overall complication rate. However, when gross total resection can be achieved, overall outcomes are excellent and the recurrence rate is low.

Long-term tumor control after endoscopic endonasal resection of craniopharyngiomas: comparison of gross-total resection versus subtotal resection with radiation therapy

2021 ◽  
pp. 1-9
Author(s):  
Saniya S. Godil ◽  
Umberto Tosi ◽  
Mina Gerges ◽  
Andrew L. A. Garton ◽  
Georgiana A. Dobri ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Diabetes Insipidus ◽  
Endocrine Function ◽  
Gross Total Resection ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Total Resection ◽  
Endoscopic Endonasal

OBJECTIVE Surgical management of craniopharyngiomas (CPAs) is challenging. Controversy exists regarding the optimal goals of surgery. The purpose of this study was to compare the long-term outcomes of patients who underwent gross-total resection with the outcomes of those who underwent subtotal resection of their CPA via an endoscopic endonasal approach. METHODS From a prospectively maintained database of all endoscopic endonasal approaches performed at Weill Cornell Medicine, only patients with CPAs with > 3 years of follow-up after surgery were included. The primary endpoint was radiographic progression. Data were collected on baseline demographics, imaging, endocrine function, visual function, and extent of resection. RESULTS A total of 44 patients with a mean follow-up of 5.7 ± 2.6 years were included. Of these patients, 14 (31.8%) had prior surgery. GTR was achieved in 77.3% (34/44) of all patients and 89.5% (34/38) of patients in whom it was the goal of surgery. Preoperative tumor volume < 10 cm3 was highly predictive of GTR (p < 0.001). Radiation therapy was administered within the first 3 months after surgery in 1 (2.9%) of 34 patients with GTR and 7 (70%) of 10 patients with STR (p < 0.001). The 5-year recurrence-free/progression-free survival rate was 75.0% after GTR and 25.0% after STR (45% in subgroup with STR plus radiotherapy; p < 0.001). The time to recurrence after GTR was 30.2 months versus 13 months after STR (5.8 months in subgroup with STR plus radiotherapy; p < 0.001). Patients with GTR had a lower rate of visual deterioration and higher rate of return to work or school compared with those with STR (p = 0.02). Patients with GTR compared to STR had a lower rate of CSF leakage (0.0% vs 30%, p = 0.001) but a higher rate of diabetes insipidus (85.3% vs 50%, p = 0.02). CONCLUSIONS GTR, which is possible to achieve in smaller tumors, resulted in improved tumor control, better visual outcome, and better functional recovery but a higher rate of diabetes insipidus compared with STR, even when the latter was supplemented with postoperative radiation therapy. GTR should be the goal of craniopharyngioma surgery, when achievable with minimal morbidity.

Diagnosis and Management of Pineocytomas

Neurosurgery ◽  
2004 ◽  
Vol 55 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Vivek R. Deshmukh ◽  
Kris A. Smith ◽  
Harold L. Rekate ◽  
Stephen Coons ◽  
Robert F. Spetzler
Keyword(s):  
Tumor Resection ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Pineal Tumors ◽  
Time To Recurrence ◽  
Tectal Plate ◽  
The Mean ◽  
Mean Time

Abstract OBJECTIVE: Pineocytomas are associated with the most favorable prognosis of all pineal tumors. However, a subset of pineocytomas may have a predilection for recurrence and therefore behave aggressively. PATIENTS AND METHODS: Records of nine patients (five men, four women; mean age, 44 yr; range, 24–63 yr) with histologically diagnosed pineocytomas consecutively treated between 1990 and 2003 were reviewed retrospectively to identify factors predictive of aggressiveness. Eight patients presented with hydrocephalus and four with tectal compression. Three patients underwent gross total resection, and six underwent subtotal resection or biopsy. RESULTS: Three local recurrences necessitated reoperation. One recurrence involved the obex of the fourth ventricle. The mean time to recurrence was 3.5 years (range, 1–7 yr). There was no correlation between histological features and tumor recurrence. Patients undergoing radiosurgery showed stable or attenuated local disease (mean follow-up, 19.3 mo; range, 6–36 mo). Mean radiographic follow-up was 34 months (range, 6 mo to 10 yr). Mean clinical follow-up was 36 months (range, 1 mo to 10 yr). CONCLUSION: A subset of pineocytomas demonstrates the potential for symptomatic recurrence. We advocate an attempt at gross total tumor resection for all symptomatic patients with tectal plate compression, reserving radiosurgery for small, subtotally resected, or recurrent lesions. Patients must be followed closely for recurrence. Radiosurgery seems to be beneficial for local tumor control. Further investigation is needed to identify histological markers for pineocytomas that behave aggressively.

Prospective trial of gross-total resection with Gliadel wafers followed by early postoperative Gamma Knife radiosurgery and conformal fractionated radiotherapy as the initial treatment for patients with radiographically suspected, newly diagnosed glioblastoma multiforme

2008 ◽  
Vol 109 (Supplement) ◽  
pp. 106-117 ◽  
Author(s):  
Kris A. Smith ◽  
Lynn S. Ashby ◽  
L. Fernando Gonzalez ◽  
David G. Brachman ◽  
Terry Thomas ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Local Control ◽  
Initial Treatment ◽  
Gamma Knife Radiosurgery ◽  
Local Tumor Control ◽  
Gross Total Resection ◽  
Tumor Control ◽  
Local Tumor ◽  
Total Resection ◽  
Fractionated Radiotherapy

Object The purpose of this study was to determine whether increased local control and improved survival can be achieved in patients with glioblastoma multiformes (GBMs) who undergo aggressive resection, Gliadel wafer implantation, Gamma Knife radiosurgery (GKS), and fractionated radiotherapy (RT) as the initial treatment. Methods Thirty patients with radiographically suspected GBMs were screened for enrollment in a Phase I/II prospective clinical trial. Twenty-seven patients were eligible and underwent gross-total resection and Gliadel wafer implantation. Gamma Knife radiosurgery (12 Gy at 50%) was administered to the resection cavity within 2 weeks of surgery. Patients then received standard fractionated RT (total dose 60 Gy over 6 weeks). Temozolomide was prescribed for patients at the time of recurrence. Surveillance MR imaging, neurological examination, and quality-of-life evaluations were performed at 2-month intervals. To estimate the potential effects on the DNA repair mechanism, tumor tissue was analyzed with methylation-specific polymerase chain reaction analysis and immunohistochemical assays for MGMT gene promoter methylation and protein expression. Results The median survival for all patients was 50 weeks and the 2-year survival rate was 22%. When stratified into standard and high-risk patient groups, the median survivals were 76 and 33 weeks, respectively. Two patients remain alive at the time of this report with no clinical or radiographic evidence of disease at > 189 and 239 weeks posttreatment and excellent performance status. Local tumor control was achieved in 53% of patients, and local failure occurred in 47%. No acute early toxicity was noted; however, delayed symptomatic radionecrosis occurred in 47% of patients, which required repeated operations 9–24 months after the initial treatment. Delayed hydrocephalus requiring ventriculoperitoneal shunt placement occurred in 47% of patients. There was a significant difference in survival between patients whose tumors contained the methylated and unmethylated MGMT promoter, 103 versus 45 weeks, respectively (p = 0.0009, log-rank test). Conclusions The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone. Delayed focal radionecrosis was increased to 47% in this series and was managed with steroids and repeated resection. Aggressive local tumor control with these multimodal therapies should be approached judiciously for a select group of high performance patients and the probability of developing symptomatic radionecrosis requiring surgery should be anticipated and fully disclosed to patients who undergo this treatment.

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