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RADIOSURGERY AS DEFINITIVE = MANAGEMENT OF=20 INTRACRANIAL MENINGIOMAS

[CLINICAL STUDIES]

Kondziolka, Douglas M.D., M.Sc.; = Mathieu,=20 David M.D.; Lunsford, L. Dade M.D.; Martin, Juan J. M.D.; Madhok, = Ricky=20 M.D.; Niranjan, Ajay M.Ch.; Flickinger, John C. M.D.

Departments of Neurological = Surgery and=20 Radiation Oncology, and The Center for Image-guided Neurosurgery,=20 University of Pittsburgh, Pittsburgh, Pennsylvania (Kondziolka) = (Martin)=20 (Flickinger)

Department of Neurological = Surgery, The Center=20 for Image-guided Neurosurgery, University of Pittsburgh, = Pittsburgh,=20 Pennsylvania (Mathieu) (Lunsford) (Madhok) (Niranjan)

Reprint = requests: Douglas Kondziolka, M.D., M.Sc., Department of=20 Neurological Surgery, Suite B-400, UPMC, 200 Lothrop Street, = Pittsburgh,=20 PA 15213. Email: kondziolkads@upmc.edu

Received,=20 April 5, 2007.

Accepted,=20 August 1, 2007.

Article Outline=20

Abstract=20
PATIENTS=20 AND METHODS=20
RESULTS=20
- Adjuvant=20 Radiosurgery
- Primary=20 Radiosurgery
- Complications=20
- Multivariate=20 Analyses
DISCUSSION=20
- Indications=20 for Radiosurgery
Acknowledgments=20
REFERENCES=20
- COMMENTS=20
Citing=20 Articles

Figures/Tables=20

Abstract TOP=20

OBJECTIVE: Stereotactic = radiosurgery has=20 become an important primary or adjuvant minimally invasive = management=20 strategy for patients with intracranial meningiomas with the goals = of=20 long-term tumor growth prevention and maintenance of patient = neurological=20 function. We evaluated clinical and imaging outcomes of = meningiomas=20 stratified by histological tumor grade.

METHODS:=20 The patient cohort consisted of 972 patients with 1045 = intracranial=20 meningiomas managed during an 18-year period. The series included = 70%=20 women, 49% of whom had undergone a previous resection and 5% of = whom had=20 received previous fractionated radiation therapy. Tumor locations = included=20 middle fossa (n =3D 351), posterior fossa (n =3D 307), convexity = (n =3D 126),=20 anterior fossa (n =3D 88), parasagittal region (n =3D 113), or = other (n =3D=20 115).

RESULTS:=20 The overall control rate for patients with benign meningiomas = (World=20 Health Organization Grade I) was 93%. In those without previous=20 histological confirmation (n =3D 482), tumor control was 97%. = However, for=20 patients with World Health Organization Grade II and III tumors, = tumor=20 control was 50 and 17%, respectively. Delayed resection after = radiosurgery=20 was necessary in 51 patients (5%) at a mean of 35 months. After 10 = years,=20 Grade 1 tumors were controlled in 91% (n =3D 53); in those without = histology, 95% (n =3D 22) were controlled. None of the patients = developed a=20 radiation-induced tumor. The overall morbidity rate was 7.7%. = Symptomatic=20 peritumoral imaging changes developed in 4% of the patients at a = mean of 8=20 months.

CONCLUSION: Stereotactic = radiosurgery=20 provided high rates of tumor growth control or regression in = patients with=20 benign meningiomas with low risk. This study confirms the role of=20 radiosurgery as an effective management choice for patients with = small to=20 medium-sized symptomatic, newly diagnosed or recurrent meningiomas = of the=20 brain.

Meningiomas are common = intracranial tumors=20 that may pose therapeutic challenges for patients and their = physicians.=20 During the past 80 years, craniotomy and removal of a meningioma = and its=20 dural base became the preferred treatment for symptomatic patients = (23).=20 Microsurgery and image-guidance techniques have reduced the = morbidity=20 associated with resections of smaller tumors and the mortality = after=20 resections of large tumors. Because these usually benign tumors = may be=20 associated closely with critical neural or vascular structures, = complete=20 resection may not be feasible (1,11,20,22).=20 Meningiomas adjacent to venous sinuses may be resectable only at = the risk=20 of major neurological deficits caused by venous injury. For = elderly,=20 infirm patients or those not eligible for resection, alternative = or=20 adjuvant strategies were necessary. This report reviews our = experience=20 using radiosurgery for the management of more than 1000 = intracranial=20 meningiomas, stratified by the use of radiosurgery as the primary = or=20 adjuvant care and by tumor histological grade.

PATIENTS AND METHODS TOP=20

This study was performed with the = approval of=20 the University of Pittsburgh Institutional Review Board. The = records and=20 imaging results were collected prospectively and then reviewed by = three=20 neurosurgeons (DM, JM, RM) who had not participated in the care of = these=20 patients. During an 18-year interval, 972 patients with 1045 = meningiomas=20 underwent stereotactic radiosurgery. The brain locations of these = tumors=20 are shown in Table=20 1. The decision to perform radiosurgery was made in patients = with=20 residual or recurrent smaller volume tumors after previous = resection,=20 those with symptomatic primary tumors in locations associated with = higher=20 risk for resection, those with concomitant medical illnesses or = advanced=20 age, in younger patients who chose radiosurgery over other = available=20 options, and in younger patients with minimal symptoms or who were = asymptomatic but chose against observation. Contraindications or = exclusion=20 criteria included large tumor volume (mean diameter >3.5 cm), = tumors=20 with symptomatic optic nerve or chiasmal compression, optic nerve = sheath=20 tumors with preserved vision, elderly patients with asymptomatic = tumors,=20 or tumors with atypical imaging features and no prior histological = diagnosis. The detailed results from 982 tumors (94%) were = available for=20 analysis. The mean patient age was 57 years (maximum, 90 yr). = Tumors were=20 diagnosed in 683 women (70%) and 299 men (30%). Five hundred and = four=20 patients (51%) had no previous treatment. Previous surgical = resections=20 were usually partial tumor removals (84%). A solitary tumor was = present in=20 818 patients, and multiple tumors were present in 161. = Twenty-eight=20 patients had neurofibromatosis Type 2. Tumor pathology was known = in 511=20 residual or recurrent tumors. Men were found to have a higher rate = of=20 atypical and malignant meningiomas. Of 317 tumors in men, 49 = (15.5%) were=20 Grades II or III, whereas for women, the incidence was 5.2% (38 = out of 729=20 tumors). Previous radiotherapy (RT) had been delivered to 54 = patients (48=20 after a resection and six had RT alone); two patients had = undergone=20 previous radiosurgery elsewhere. Eight patients had received = chemotherapy.=20 Twenty-five tumors (2.5%) developed after previous fractionated=20 irradiation.

TABLE 1. Locations of 1045 = intracranial meningiomas

Radiosurgery was performed under = local=20 anesthesia with mild sedation as necessary, using a Leksell Gamma = Knife=20 (Elekta Instruments, Inc., Atlanta, GA). After application of the = Leksell=20 Model G stereotactic frame, high-resolution, volume acquisition=20 stereotactic magnetic resonance imaging scans were obtained. = Before 1991,=20 we performed radiosurgery using stereotactic computed tomographyic = (CT)=20 guidance. Image integrated isodose plans were created to enclose = the=20 irregular tumor borders. A mean of 7.5 isocenters were used to = provide=20 conformal radiosurgery. The dose received by adjacent critical = structures=20 was determined, and selective beam blocking was used if necessary = to=20 restrict the dose fall-off. The maximal and marginal dose was = selected by=20 the neurosurgeon, radiation oncologist, and medical physicist. We=20 delivered a mean dose to the tumor margin of 14 Gy and a mean = maximum dose=20 of 28 Gy. The mean tumor volume in this series was 7.4 mL. The = mean volume=20 receiving more than 12 Gy was 8.4 mL. Radiation doses were = prescribed to=20 the 50% isodose volume for 886 tumors (85%). For tumors near the = optic=20 nerve or chiasm, the average maximal optic dose was 6.4 Gy. After=20 radiosurgery, patients were discharged home within 24 hours; in = recent=20 years, they were discharged on the same day. Follow-up imaging = studies=20 were initially obtained at 6 months after radiosurgery, 1-year = intervals=20 for the first 2 years, and at intervals of 3 to 4 years = thereafter. The=20 median follow-up period in this study was 4 years; 842 patients = were still=20 living (86%). Follow-up for more than 5, 7, 10, and 12 years was = obtained=20 in 327, 190, 90, and 41 patients, respectively. Clinical follow-up = was=20 obtained at our center or by the referring physicians.

Actuarial plots were created = using the Kaplan=20 and Meier method. Univariate comparisons between groups were = performed=20 using the log rank test. Forward stepwise multivariate analysis = was=20 performed using the Cox proportional hazards model. Time to tumor=20 progression was coded at the time of the imaging study that showed = progression, i.e., time of documentation rather than time of = initial=20 regrowth.

RESULTS TOP=20

Imaging studies after = radiosurgery showed=20 that 407 tumors had regressed, 454 were unchanged, and 96 had = enlarged,=20 for a raw tumor control rate of 90%. Actuarial tumor control, = survival,=20 and disease-specific survival by World Health Organization (WHO) = grade are=20 shown in Figures=20 1-3. Imaging and clinical follow-up was requested for all = patients,=20 but was not complete for all.

FIGURE 1. Graph showing = intracranial=20 tumor control after gamma knife radiosurgery, plotted = according to=20 World Health Organization (WHO) grade. Grade 0 refers to = tumors=20 without histological = confirmation.

FIGURE 2. Graph showing = tumor-specific=20 survival, with death related to tumor effects or = progression, after=20 gamma knife radiosurgery, plotted according to WHO=20 grade.

FIGURE 3. Graph showing = patient=20 survival after gamma knife radiosurgery, plotted according = to WHO=20 grade.

Adjuvant Radiosurgery TOP=20

Based on previous histopathology, = we had 424=20 WHO Grade I meningiomas in this series, 384 of which were = available for=20 study. We found that 172 tumors had regressed, 186 were unchanged, = and 26=20 had enlarged, for a tumor control rate of 93% at a median of 4 = years.=20 Ninety-one percent of the patients were either clinically improved = (n =3D=20 21) or unchanged (n =3D 341). Imaging follow-up past 8 and 10 = years was=20 obtained in 79 and 53 tumors, respectively, both with a control = rate of=20 91% (Figs.=20 4 and 5). Past ten years, 45 patients were stable, six were = improved,=20 and two were worse. For Grade I meningiomas, the 5-, 10-, and = 15-year=20 actuarial tumor control rates were 97 =C2=B1 1.2, 87.2 =C2=B1 4.4, = and 87.2 =C2=B1 4.4%,=20 respectively. Disease specific survival was 98.9 =C2=B1 0.5, 96.2 = =C2=B1 1.9, and=20 96.2 =C2=B1 1.9%, respectively.

FIGURE 4. Coronal = contrast-enhanced=20 magnetic resonance imaging scan at the time of radiosurgery = (A) and 14 years later (B) showing the response to a = residual=20 meningioma (arrow) around the = anterior=20 communicating artery complex. Radiosurgery was performed = using two 8=20 mm isocenters and a tumor margin dose of 15=20 Gy.

FIGURE 5. Axial computed = tomgraphic=20 scan at the time of radiosurgery (A) and a magnetic resonance = imaging scan 18=20 years later (B) showing = tumor=20 regression for a residual petrous ridge meningioma after = previous=20 resection.

Of 56 WHO Grade II tumors, 54 = were available=20 for review. Sixteen had regressed, 11 were unchanged, and 27 had = enlarged,=20 resulting in a tumor control rate of 50% at a median of 2 years. = During=20 the follow-up period, 72% of these patients were stable = clinically. Of 31=20 WHO Grade III tumors, 29 were reviewed. We found that four = regressed, one=20 was stable, and 24 later enlarged, resulting in a tumor control = rate of=20 17% at a median of 15 months.

Primary Radiosurgery TOP=20

There were 536 tumors that = received=20 radiosurgery as primary management without previous histological=20 confirmation. All patients had typical contrast-enhancing, dural = based=20 tumors. We were able to evaluate later serial images for 488 = tumors. We=20 found that 215 tumors had regressed, 256 were unchanged, and 19 = had=20 enlarged, resulting in a tumor control rate of 97% at a median of = 4 years.=20 Ninety-three percent of patients with these tumors either improved = neurologically (n =3D 87) or remained unchanged (n =3D 380). There = was no=20 difference in the tumor response between male and female patients. = Follow-up imaging past 8 and 10 years was obtained in 49 and 22 = tumors,=20 respectively, with control rates of 94 and 95%. Past 10 years, 16 = patients=20 were stable, three were improved, and three were worse. When = recurrence=20 after primary radiosurgery did occur, it was not typically from = the=20 contrast-enhancing dural tail adjacent to many meningiomas, = particularly=20 at the cranial base.

Subsequent surgical resection was = performed=20 in 51 patients (5.2%) due to local tumor growth or increased = symptoms at=20 an average time of 35 months. Additional fractionated radiotherapy = was=20 used in 2.9% at an average of 32 months. Further radiosurgery was=20 performed in 41 patients (4%), usually for new tumors, at an = average of 49=20 months. Eight patients later received chemotherapy (0.8%). None of = the=20 patients developed a radiation-induced tumor.

Complications TOP=20

After radiosurgery, all patients = returned to=20 their preoperative activities immediately. After radiosurgery, = nausea or=20 other immediate symptoms were rare. One patient developed = pneumonia 1 week=20 after radiosurgery and died. A complication attributed to = radiosurgery was=20 observed in 76 patients (7.7%) at an average time of 11 months. = The=20 morbidity rates for cavernous sinus location and parasagittal = locations=20 were 6.3 and 9.7%, respectively. For cavernous sinus tumors, these = included cranial nerve deficits in 12 patients. Four of these had=20 diplopia, and two had trigeminal neuropathy (one of whom had = neuralgic=20 pain). Six patients had decreased visual acuity, four of whom had = previous=20 treatment that included multiple resections (n =3D 3), multiple=20 radiosurgeries (2),=20 radiation therapy (n =3D 3), and chemotherapy (n =3D 1).

The 10- and 15-year actuarial = complication=20 rates were both 9.1%. Specifically, hydrocephalus was found in = 0.4%, a=20 cranial nerve deficit in 3.4%, headaches in 2.2%, seizures in = 2.4%, a=20 motor deficit in 1.4%, and a sensory deficit in 0.3%. A=20 ventriculoperitoneal shunt was placed in five patients (0.5%) at = an=20 average of 20 months. Complete resolution of symptoms was noted in = 35% of=20 patients who sustained morbidity. Imaging showed interval = development of=20 tumoral signal abnormalities determined by long relaxation time = magnetic=20 resonance imaging scans in 6.2% of the patients, with 4% of the = total=20 series having symptomatic imaging changes at an average of 8 = months.

Multivariate Analyses TOP=20

The results of multivariate = analyses of=20 survival, disease free survival, and local control are shown in Table=20 2. Worse overall survival significantly correlated with = increasing age=20 (P =3D 1.206 =C3=97 10^-20=20 hazard ratio [HRR] =3D 1.073 per year [95% confidence interval, = 1.057-1.089=20 per yr]), increasing WHO Grade 0 to III (0 for no tissue = diagnosis) (P =3D 3.9385 =C3=97 10^-11, HRR =3D=20 2.002 [1.629-2.460] per grade), and increasing volume (P =3D 0.0407, HRR =3D 1.0416 [1.022-1.062] = per cm3). Worse disease-specific survival = correlated with=20 WHO Grade 0 to III (P =3D 6.138 =C3=97 = 10-25, HRR =3D 5.910 [4.217-8.284] per = grade), increasing=20 age (P =3D 0.001528, HRR =3D 1.045 = [1.016-1.074] per=20 year), and with multiple meningiomas (P = =3D=20 0.02754, HRR =3D 2.208 [1.092-4.465]. Poorer intracranial tumor = control=20 correlated with increasing WHO Grade 0 to III (P=20 =3D 5.236 =C3=97 10^-27, HRR =3D 3.962 = [3.084-5.093] per=20 grade), increasing volume (P =3D = 0.1190, HRR =3D=20 1.030 [1.007-1.054] per cm³), and with = multiple=20 meningiomas (P =3D 0.03589, HRR =3D = 1.782=20 [1.039-3.058]. The actuarial plots for intracranial tumor control = and=20 disease-specific survival according to WHO grade are shown in Figures=20 1 and 2.

TABLE 2. Multivariate = analyses of=20 overall survival, disease-specific survival, and local = control=20 defined as freedom from further surgery, radiotherapy, = radiosurgery,=20 chemotherapy, or death from disease^a=20

Univariate and multivariate = analyses of=20 postradiosurgery complications and new T2-weighted imaging changes = are=20 shown in Table=20 3. Both volume and 12-Gy volume significantly correlated with = the=20 development of postradiosurgery complications and new T2-weighted = changes=20 in univariate testing (P < 0.0001), = whereas in=20 multivariate analysis, volume correlated with complications (P =3D 5.268 =C3=97 10^-7, HRR =3D=20 1.068 [1.041-1.095] per cm³) and 12-Gy = correlated with new T2-weighted changes volume (P=20 =3D 4.066 =C3=97 10^-6, HRR =3D 1.057 = [1.032-1.083] per=20 cm³).

TABLE 3. Uni- and = multivariate=20 analyses of the probability developing symptomatic = complications or=20 new imaging changes after meningioma radiosurgerya =

DISCUSSION TOP=20

Indications for Radiosurgery = TOP=20

Over the past two decades, the = indications=20 for meningioma radiosurgery have expanded to patients with newly = diagnosed=20 tumor as opposed to recurrent or residual tumors after initial = resection=20 (2,4,5,7,9,12-15,17-19,= 24-26,28,31,32).=20 Those patients undergoing primary radiosurgery had imaging = findings that=20 were typical of a meningioma. In long-term follow-up evaluation, = we found=20 that the initial imaging-based diagnosis of a benign meningioma = was in=20 error in 2.3%, usually proven to be a higher grade meningioma (6).=20 As primary management, radiosurgery is not appropriate for = patients with=20 large meningiomas, for patients with significant symptomatic mass = effect,=20 and for patients with optic nerve sheath tumors and preserved = vision.=20 Although some surgeons advocate tumor debulking in symptomatic = patients=20 who are then simply followed to see if the residual tumor = enlarges, the=20 literature substantiates high recurrence and progression rates = after such=20 management. Condra et al. (3)=20 found a 70% rate of tumor progression after subtotal resection = without=20 fractionated radiation therapy. Other groups have noted the value = of=20 postresection irradiation (8,21).=20 A recent series found a 4 mm mean annual rate of tumor growth = after=20 partial resection of a basal meningioma (10).=20 We advocate that the entire neoplasm be treated using the most = appropriate=20 modalities, when safe and feasible, including complete resection,=20 resection plus radiosurgery for residual tumors, or radiosurgery = alone for=20 small volume tumors in critical locations. We believe that this = strategy=20 will provide better long term outcomes than managing only a = portion of the=20 tumor. For these reasons, we explored the role of radiosurgery for = patients with tumors in locations not amenable to surgical cure, = locations=20 at high risk for neurological deficits, those with residual or = recurrent=20 tumors, and those with growing tumors and adverse medical risk = factors for=20 resection.

Radiosurgery was thought to have = only an=20 adjuvant role for patients with resectable meningiomas located in=20 convexity, falcine, or anterior fossa regions. However, patients = with=20 tumors in such locations often choose radiosurgery. Although=20 retrospective, we believe that our patient series proposes = radiosurgery as=20 an effective and safe option for such patients. Donald Simpson's = (30)=20 landmark article described meningioma recurrence rates based on = the degree=20 and description of the resection. He reported a 9% recurrence rate = after=20 complete resection of the tumor and its neoplastic dural base, a = 19%=20 recurrence rate when the tumor was resected and the dural base = only=20 coagulated, a 29% recurrence rate when the tumor itself was = removed but=20 the dura could not be excised or cauterized, and an approximate = 40%=20 recurrence rate when only a subtotal resection was performed. In = the=20 modern era, even higher recurrence rates have been reported (29).=20 Pollock et al. (27)=20 studied 136 patients after resection and 62 after radiosurgery = with a mean=20 follow-up period of 64 months. Their recurrence rates after = resection were=20 remarkably similar to the findings of Simpson more than 40 years = earlier.=20 Tumor recurrence was more frequent in the resection group (12 = versus 2%;=20 P =3D 0.04). There was no difference in = recurrence=20 rates for patients after a Simpson Grade I resection, but = radiosurgery=20 provided more durable control after Grade II resection (P < 0.05) or Grades III to IV resections = (P < 0.001) (27).=20 Thus, one could conclude that the results of radiosurgery for a = smaller=20 tumor are equal to or better than after a resection, depending on = the=20 degree of resection expected.

In a previous review of 5- to = 10-year=20 outcomes in 99 patients, we surveyed patients for their own = opinions=20 regarding outcomes (14).=20 Sixty-five patients answered our questions regarding employment.=20 Twenty-seven patients (42%) were employed at the time of = radiosurgery and=20 20 remained so (74%). Of 35 patients not employed at radiosurgery, = five=20 (14%) resumed employment. Patients described their overall level = of=20 activity as remaining unchanged in 65%, being increased in 8%, or=20 decreased in 27%. Radiosurgery was described as a successful = treatment by=20 67 out of 70 patients (96%) (14).=20 Patients undergoing outpatient radiosurgery have not been exposed = to the=20 risks related to an open surgical exposure, brain retraction, = anesthesia,=20 or a prolonged hospital stay.

Long-term Expectations TOP=20

How long should such tumors be = followed with=20 serial imaging? After 10 years, we request an imaging assessment = every 4=20 years. In patients with histologically confirmed Grade 1 tumors, = or those=20 without previous biopsy, the tumor control rates past 10 years = were 91 and=20 95%, respectively. Thus, the chance for late regrowth should be = low;=20 however, for patients managed with any technique, the risk for = recurrence=20 or the development of a new tumor remains. Although we have not = observed=20 the development of a secondary, radiation-induced tumor at or near = the=20 radiosurgery target volume, we caution patients over this small = risk (16).

In conclusion, stereotactic = radiosurgery is a=20 powerful biological approach for a patient with an intracranial = meningioma=20 that is well tolerated and can be performed on an outpatient = basis.=20 Excellent long-term outcomes can be expected in the majority of = patients.=20 In this large series of selected patients, the tumor response = after=20 radiosurgery for a primary or histologically confirmed benign = tumor was as=20 good as or better than that expected after any degree of = resection.=20 Radiosurgery should be considered an effective management choice = for=20 patients with smaller tumors, particularly in critical brain=20 locations.

Acknowledgments TOP=20

We thank the staff of the Center = for=20 Image-guided Neurosurgery, whose diligent work enabled the care of = patients in this study. Douglas Kondziolka, M.D., M.Sc., L. Dade = Lunsford,=20 M.D., and Ajay Niranjan, M.Ch., have a consulting agreement with = Elekta=20 Instruments, Inc.

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25. Pendl G, Schr=C3=B6ttner O, = Eustacchio S,=20 Feichtinger K, Ganz J: Stereotactic radiosurgery of skull base=20 meningiomas. Minim Invasive = Neurosurg=20 40:87-90, 1997.=20

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26. Pollock BE, Stafford SL: = Results of=20 stereotactic radiosurgery for patients with imaging defined = cavernous=20 sinus meningiomas. Int J Radiat Oncol = Biol=20 Phys 62:1427-1431, 2005.=20

[Context=20 Link]

27. Pollock BE, Stafford SL, Utter = A, Giannini=20 C, Schreiner SA: Stereotactic radiosurgery provides equivalent = tumor=20 control to Simpson Grade 1 resection for patients with small to = medium=20 size meningiomas. Int J Radiat Oncol = Biol=20 Phys 55:1000-1005, 2003.=20

[Med= line=20 Link] [CrossRef]=20 [Context=20 Link]

28. Roche PH, R=C3=A9gis J, Dufour = H, Fournier HD,=20 Delsanti C, Pellet W, Grisoli F, Peragut JC: Gamma knife = radiosurgery in=20 the management of cavernous sinus meningiomas. J=20 Neurosurg 93 [Suppl 3]:68-73, 2000.=20

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29. Sankila R, Kallio M, = J=C3=A4=C3=A4skel=C3=A4inen J,=20 Hakulinen T: Long-term survival of 1986 patients with intracranial = meningioma diagnosed from 1953 to 1984 in Finland. Comparison of = the=20 observed and expected survival rates in a population-based series. = Cancer 70:1568-1576, 1992.=20

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30. Simpson D: The recurrence of = intracranial=20 meningiomas after surgical treatment. J = Neurol=20 Neurosurg Psychiatry 20:22-39, 1957.=20

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31. Subach BR, Lunsford LD, = Kondziolka D,=20 Bissonette DJ, Flickinger JC: Stereotactic radiosurgery for = petroclival=20 meningiomas. Neurosurgery = 42:437-445,=20 1998.=20

[Fulltext=20 Link] [Medline=20 Link] [CrossRef]=20 [Context=20 Link]

32. Zachenhofer I, Wolfsberger S, = Aichholzer M,=20 Bertalanffy A, Roessler K, Kitz K, Knosp E: Gamma knife = radiosurgery for=20 cranial base meningiomas: Experience of tumor control, clinical = course,=20 and morbidity in a follow-up more than 8 years. Neurosurgery 58:28-36, 2006.=20

[Fulltext=20 Link] [Medline=20 Link] [CrossRef]=20 [Context=20 Link]

COMMENTS TOP=20

Kondziolka et al. have presented = another=20 landmark radiosurgery article that documents a very large = experience with=20 meningiomas. Over the course of 18 years, 972 patients were = treated. The=20 overall control rate for benign meningiomas was 93%. Notably, = control=20 rates for atypical and malignant meningiomas are much worse. These = lesions=20 will frequently recur despite maximal surgery, conventional = radiotherapy,=20 and/or radiosurgery. Overall morbidity was 7.7%, and no = radiation-induced=20 tumor has occurred. I agree that this study confirms the role of=20 radiosurgery as an effective management choice for many = meningiomas.

William A. Friedman

Gainesville, Florida

This is a retrospective review of = patients=20 with meningiomas (at all sites) who were treated with stereotactic = radiosurgery at a single institution. The article is well written = and=20 includes a large number of patients who were treated by this very = strong=20 Pittsburgh group. It is already well known that radiosurgery is = effective=20 against meningiomas, and this modality is commonly used in the = treatment=20 of these tumors. The control rates and the median follow-up = periods cited=20 are in line with previous reports.

The strength of this article is = the sample=20 number; however, in gaining these numbers, Kondziolka et al. = lumped=20 meningiomas from all sites. Each meningioma site (e.g., cavernous = versus=20 convexity versus tuberculum sellae) is almost like a separate = disease,=20 with a different natural history, a different set of potential=20 complications, and, consequently, a distinct treatment paradigm. = The=20 authors extrapolate carefully from this massed data to conclude = that=20 radiosurgery should be considered an effective choice in the = management of=20 meningiomas. I do not think anyone could disagree with this = statement at=20 this stage in the evolution of this powerful technique.

Philip H. Gutin

New York, New York

In this article, Kondziolka et = al. present a=20 comprehensive analysis of the safety and efficacy of gamma knife = surgery=20 for the treatment of meningiomas. As neurosurgeons, we must keep = in mind=20 that the interests of all patients may not be best served by a = gross total=20 resection. Rather, in many instances (e.g., cavernous sinus = meningiomas),=20 the tumor control that is achieved by radiosurgery may afford = optimal=20 neurological function and quality of life for the patient. In this = regard,=20 the overall control rate of 93% for the larger cohort of World = Health=20 Organization (WHO) Grade I meningioma patients demonstrates the = merits of=20 a stereotactic radiosurgical approach. The authors also note a = morbidity=20 rate of 7.7%, including a 3.4% rate of cranial nerve deficit. As = such, the=20 benefit-to-risk profile of stereotactic radiosurgery for WHO Grade = I=20 meningiomas is acceptable. For WHO Grade II and III meningiomas, = the=20 reported results indicate room for improvement. Radiosurgery = should not be=20 unduly criticized for diminished efficacy in higher-grade = meningiomas, as=20 the same is true for microsurgery and radiation therapy.

This study clearly indicates that = gamma knife=20 surgery alters the natural history of most meningiomas. Moreover, = the=20 response seems durable. Failure, if it is going to occur, = typically does=20 so within the first 3 years after radiosurgery.

All neurosurgeons must continue = to hone their=20 microsurgical skills. Whenever possible, gross total resection of = a=20 meningioma should remain the goal, provided that it can be = achieved with=20 comparable or lower morbidity and mortality to radiosurgery. = However, when=20 this is not possible, a subtotal resection followed by = radiosurgery or=20 upfront radiosurgery should be used. For WHO Grade I meningiomas = in=20 particular, we cannot make the cure worse than the disease.

Jason P. Sheehan

Charlottesville, Virginia

Over more than a decade, dozens = of=20 publications have provided convincing evidence to support the use = of=20 radiosurgery in selected patients with meningiomas. However, the = paucity=20 of published, long-term studies remains a common criticism of a = primary=20 radiosurgical approach to such slow-growing lesions. This fact, = and a=20 lingering fear of inducing secondary malignancies with ionizing = radiation,=20 has limited the acceptance of radiosurgery for many younger = meningioma=20 patients. The latter concern, i.e., the induction of new cancers, = was=20 somewhat allayed by the recent publication in NEUROSURGERY by Rowe et al. (1).=20 However, the significance of the current report is that it begins = to fill=20 the major void in long-term follow-up after radiosurgical = ablation. Given=20 the challenges in conducting such studies, the authors are to be=20 congratulated. I hope radiosurgery has now been used long enough = for us to=20 start anticipating that other radiosurgical centers will soon be = reporting=20 similar favorable experiences with meningiomas. If so, the = argument for=20 using radiosurgery to manage small meningiomas in all age groups = may prove=20 thoroughly compelling.

John R. Adler, Jr.

Stanford, California

1. Rowe J, Grainger A, Walton L, = Silcocks P,=20 Radatz M, Kemeny A: Risk of malignancy after gamma knife = stereotactic=20 radiosurgery. Neurosurgery = 60:60-66,=20 2007.=20

[Fulltext=20 Link] [Medline=20 Link] [CrossRef]=20 [Context=20 Link]

This is an excellent study from a = leading=20 radiosurgery group describing their experiences using radiosurgery = for the=20 management of intracranial meningiomas. Although retrospective, it = does=20 provide useful information that will help clinicians make = decisions=20 regarding if and when to use radiosurgery to treat = meningiomas.

Kondziolka et al. report an = overall control=20 rate for patients with benign meningiomas (WHO Grade I) of 93%, = but for=20 patients with WHO Grade II and III tumors, the control rates were = 50 and=20 17%, respectively. The overall morbidity rate was noted as 7.7%; = however,=20 the median follow-up period for patients with WHO Grade II and III = tumors=20 is short. The median follow-up periods are 2 years and 15 months,=20 respectively, and the 5-year actuarial control rate was 40% for = Grade II=20 tumors and 15% for Grade III tumors. In contrast, the 15-year = actuarial=20 tumor control rate for Grade I meningiomas was noted as 87%. The = method of=20 reporting tumor control could overestimate the success rate of=20 radiosurgery, as the cohort may have included asymptomatic = patients who=20 could have been followed with imaging for years before treatment = was=20 necessary.

I do have some concern regarding = using=20 radiosurgery as a definitive management for patients in whom there = has=20 been no biopsy. It is noted that the authors report an error of = 2.3% in=20 the diagnosis of benign meningioma. Personally, I very much doubt = that=20 radiosurgery replaces standard surgery as a primary treatment = option for=20 those tumors that can be relatively easily resected, although I = think it=20 is a useful adjuvant for the treatment of residual tumor within = the=20 cranial base or cavernous sinus after resection of larger cranial = base=20 tumors.

Nevertheless, this article = provides very=20 useful information that will help clinicians make their management = decisions for each individual patient. This will inevitably be = based on=20 the size of the tumor, its location, involvement of critical = vascular and=20 neural structures, ease of resectability, presenting clinical = features,=20 and the patient's individual characteristics, including age and=20 wishes.

Andrew H. Kaye

Melbourne, Australia

Over the last two decades, = radiosurgery has=20 flourished as a safe and effective option for selected = meningiomas. Why=20 then, do clinical studies on this topic continue to provoke = controversy?=20 Part of the problem is that contemporary studies (surgical case = series are=20 no exception to this) often serve as a referendum on which = strategy=20 deserves a designation as definitive or absolute. This logic = attempts to=20 impart supremacy to one technique over another, rather than = determining=20 the appropriate settings in which a clinical team skilled in all=20 techniques should rationally apply one versus another to best care = for=20 patients. Declaring a therapy for meningiomas as definitive can = obscure=20 the desired goal of selecting patient therapy through a measured = analysis=20 of risks and benefits that integrate complementary and often=20 interchangeable management strategies based on specific clinical=20 characteristics.

In this article, Kondziolka et = al., who are=20 among the most knowledgeable and experienced clinicians in the=20 radiosurgery field, present a retrospective review of 972 patients = with=20 1045 intracranial meningiomas that were managed with stereotactic=20 radiosurgery during an 18-year period. The series was 70% women, = 49% of=20 whom had a previous resection and 5% of whom had previous = fractionated=20 radiation therapy. An important observation from this study is the = low=20 rate of treatment-related complications and the absence of=20 radiation-induced tumors. Despite the large number of patients = treated,=20 the study is limited by its retrospective design incorporating a=20 heterogeneous mixture of patients without stratification of = clinical=20 features. Because patients with a wide range of inclusion criteria = are=20 analyzed collectively, including patients who decided against = other=20 treatments and asymptomatic patients who chose against = observation, the=20 implications for clinical decision-making are imprecise. This = creates=20 groups of patients that do not share important clinical features, = such as=20 location, likelihood of gross total resection, presence of = symptoms,=20 progressive disease, and presence of prior therapy, making it = difficult=20 for clinicians to benefit from the authors' extensive experience.=20 Additionally, most patients had a median follow-up of less than 4 = years,=20 which is insufficient for determining long-term efficacy for a = tumor type=20 that can often have an indolent natural history.

The authors' most provocative = conclusion for=20 clinical practice is that radiosurgery can be considered a primary = treatment modality for meningiomas without consideration for = location and=20 probability of surgical resection. That there are significant = benefits to=20 radiosurgery is no longer debatable, and the authors have = historically=20 been leaders in demonstrating this to an often skeptical mass of=20 neurosurgeons, but, as clinical therapies evolve, it is desirable = to match=20 appropriate treatment modalities to individual patients and = consider=20 complementary treatment strategies rather than embrace a debate = over=20 surgery versus radiosurgery (or even conservative management) as = the=20 definitive treatment for meningiomas in the absence of a carefully = defined=20 and unbiased context. A more appropriate conclusion of this study = might be=20 that radiosurgery plays an important role in selected patients and = may be=20 definitive in many patients. This includes an acknowledgment that = many=20 meningioma patients (e.g., those with small right frontal = convexity=20 tumors) could expect favorable outcomes from either radiosurgery, = surgery,=20 or conservative management and that there is considerable overlap = among=20 these target populations. Which management strategy is definitive = would=20 depend on characteristics specific to the individual patient.=20 Retrospective studies on preselected meningioma patients are not=20 sufficiently rigorous to support conclusions regarding definitive=20 management of this diverse and heterogeneous group of patients. We = hope=20 that future analyses from the valuable patient database in this = study will=20 clarify some of these important concerns.

Christopher E. Mandigo

Jeffrey N. Bruce

New York, New = York

Keywords:=20

Brain tumor; Meningioma;=20 Radiosurgery

Copyright =C2=A9 2008, Congress of Neurological Surgeons. All = rights=20 reserved.
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