Neurosurgical FOCUS - 24(5):E7

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May 2008 Volume 24, Number = 5

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Radiation-induced = meningioma

Felix=20 Umansky, M.D., Yigal = Shoshan,=20 M.D., Guy Rosenthal,=20 M.D., Shifra Fraifeld, = M.B.A., and Sergey = Spektor,=20 M.D., PH.D.

Department of=20 Neurosurgery, Hadassah=96Hebrew University Medical = Center,=20 Jerusalem, Israel

Abbreviations used in=20 this paper: CT =3D computed tomography; MR = =3D magnetic=20 resonance; RIM =3D radiation-induced meningioma; SM = =3D=20 spontaneous meningioma; WHO =3D World Health = Organization.

Address correspondence = to: Felix=20 Umansky, M.D., Department of Neurosurgery, = Hadassah=96Hebrew=20 University Medical Center, POB 12000, Jerusalem, = Israel 91110.=20 email: umansky@hadassah.org.il=20 or umansky@netvision.net.il.

DOI: 10.3171/FOC/2008/24/5/E7

Figures = and Tables=20

Abstract	IntroductionRadiation-Induced = Meningi...Clinical = PresentationManagement of RIMConclusionsDisclaimerReferences

3D""=20 The long-term or delayed side = effects of=20 irradiation on neural tissue are now known to include = the=20 induction of new central nervous system neoplasms. = However,=20 during the first half of the 20th century, human = neural tissue=20 was generally considered relatively resistant to the=20 carcinogenic and other ill effects of ionizing = radiation. As a=20 result, exposure to relatively high doses of x-rays = from=20 diagnostic examinations and therapeutic treatment was=20 common.

In the present article the authors = review the=20 literature relating to radiation-induced meningiomas = (RIMs).=20 Emphasis is placed on meningiomas resulting from = childhood=20 treatment for primary brain tumor or tinea capitis, = exposure=20 to dental x-rays, and exposure to atomic explosions in = Hiroshima and Nagasaki. The incidence and natural = history of=20 RIMs following exposure to high- and low-dose = radiation is=20 presented, including latency, multiplicity, = histopathological=20 features, and recurrence rates. The authors review the = typical=20 presentation of patients with RIMs and discuss unique = aspects=20 of the surgical management of these tumors compared = with=20 sporadic meningioma, based on their clinical = experience in=20 treating these lesions.

Keywords:=20 ionizing radiation; radiation-induced meningioma; = tinea=20 capitis.

Introduction	AbstractIntroduction = <<Radiation-Induced = Meningi...Clinical = PresentationManagement of RIMConclusionsDisclaimerReferences

The discovery of = roentgen=20 rays, or x-rays, is credited to Wilhelm Conrad = Roentgen, who=20 noticed in November 1895 that a fluorescent screen on = a nearby=20 table began to glow when free electrons were generated = in a=20 vacuum tube. Roentgen's discovery created a furor. = During 1896=20 alone, the use of x-rays was described in nearly 1000 = articles=20 in leading scientific journals, textbooks on x-rays = and=20 radioactivity, and newspapers worldwide.³⁸

Within months, Henry Becquerel attributed fogging = on=20 unexposed photographic plates in his lab to an = invisible=20 emission from uranium. Marie and Pierre Curie = discovered other=20 radioactive elements and developed techniques to = purify radium=20 from pitchblende. Many other brilliant scientific = discoveries=20 followed=97more than 20 Nobel prizes were awarded for = research=20 relating to x-rays and radiation during the 20th = century. With=20 the discovery of the phenomenon of nuclear fission in = Germany=20 in 1938, and the first demonstration at the University = of=20 Chicago during the 1940s, the nuclear age began.

Roentgen's discovery quickly led to the invention = of x-ray=20 machines to image structures in the body and treat = health=20 conditions. Broad diagnostic and therapeutic benefits = were=20 apparent immediately. For many years, radiation was = used=20 freely for medical applications in very large doses, = with no=20 protection for patients, physicians, or auxiliary = personnel=20 (Fig.=20 1). For example, at least as late as 1930, women = were=20 exposed to radiation during pregnancy for the = treatment of=20 pelvic disease. A high incidence of anomalies was = later=20 reported among children who were thus irradiated in=20 utero.¹⁹

View=20 larger version = (138K)

Fig. 1. = Left:=20 Photograph of Mihran Kassabian, director = of the=20 Roentgen Ray Laboratory at the = Philadelphia=20 Hospital. He performed x-ray examinations = in more=20 than 3000 patients. Right: He = photographed=20 and documented damage to his hands, = including=20 progressive necrosis and serial = amputations. He=20 died of radiation-induced cancer in 1911. = Used=20 with permission of the copyright holder, = Radiology=20 Centennial, Inc.

Radium also became a marketer's dream, and products = such as=20 bottled radium water, toothpaste, suppositories, and = glowing=20 radium cocktails were popular.¹¹

There was early evidence that x-rays could harm = tissue.=20 Many radiography workers developed skin lesions and = even lost=20 their fingers. Thomas Edison, a prolific American = inventor and=20 businessman, is credited with designing and producing = the=20 first commercially available fluoroscope. His basic = design is=20 still in use, but he abandoned his work with x-rays in = 1903=20 after his own eyesight was damaged and his assistant, = Clarence=20 Dally, lost an arm, fingers, and eventually his life = due to=20 extensive experiments with x-rays (Fig. 2). = Edison=20 said at the time, =93Don't talk to me about x-rays, I = am afraid=20 of them.=94¹⁵

View=20 larger version = (90K)

Fig. 2. = Thomas Edison=20 (left), credited with invention of = the=20 fluoroscope, abandoned his work with = x-rays after=20 his own eyesight was damaged. His = assistant,=20 Clarence Dally (center), lost = fingers, then=20 an arm, and eventually his life to = metastatic skin=20 cancer. Fluoroscopists tested the = calibration of=20 their instruments by placing their hands = in the=20 rays' path (right). Used with = permission of=20 the copyright holder, Radiology = Centennial,=20 Inc.

Precautionary measures were suggested in Germany as = early=20 as 1913.²³ In=20 several British studies examining the effects of = total-body=20 irradiation on radiologists, investigators reported = relatively=20 shorter life spans in those entering the specialty = before=20 exposure standards were established in the United = Kingdom in=20 1921.³⁴ Formal=20 guidelines were established in the US during the = 1930s.²³ Over the=20 years, there has been a trend toward more rigorous = protection=20 standards after the recognition of the long-term = health=20 effects due to exposure to radiation.²⁵

Additional evidence of risk from x-ray exposure = emerged in=20 1927, when Hermann Joseph Muller (1890=961967), a = founder of=20 20th century genetics, published evidence in = Science=20 that x-ray exposure produced a 150-fold increase in = the=20 natural mutation rate of fruit flies and that the rate = of=20 mutations was proportional to the dose.⁴⁰ He=20 showed that x-rays broke apart and rearranged the = genes. In=20 1946, this research was recognized with the Nobel = Prize in=20 Medicine. Muller spoke against needless exposure to = x-rays in=20 medicine and urged protection for individuals = routinely=20 exposed to ionizing radiation.

Neurological tissue was long considered relatively=20 resistant to damage from x-rays,^16,24,45 and some=20 authors suggested that higher doses allowed longer = survival in=20 patients with glioblastoma multiforme.^6,61 In 1938,=20 Davidoff et al.¹³=20 described the clinical and histological effects of = delivering=20 10=9650 Gy in a single exposure, or 48=9672 Gy in 2 = fractions,=20 applied directly to the brains and spinal cords in = monkeys.=20 The authors observed profound physiological and = morphological=20 changes, which were especially marked in the glia and = nerve=20 tissues. The intensity of histological change was = determined=20 primarily by x-ray dose and, to a lesser extent, by = the time=20 lapsed between irradiation and autopsy. Clinical and=20 histological changes were progressive. Other authors = also=20 documented pronounced degenerative effects on nerve = tissue=20 from exposure to ionizing radiation.^31,46,79

However, only after atomic bombs were dropped on = Nagasaki=20 and Hiroshima, and atomic tests were performed during = the=20 1950s, did the general public and much of the medical=20 community became aware of risks from exposure to = ionizing=20 radiation.^4,34,43 In 1956,=20 the Committee on Biological Effects of Atomic = Radiation of the=20 National Academy of Sciences introduced the concept of = regulating the overall dose to the general population, = suggesting a 0.1-Gy limit during the reproductive = years, a=20 span averaging 30 years.⁴⁴

Today we know that exposure to ionizing radiation = overcomes=20 the binding energy of electrons orbiting atoms and = molecules.=20 In biological material, hydroxyl radicals formed by = x-ray=20 interaction with water molecules cause strand breaks = or base=20 damage in nearby DNA. The x-rays may also ionize DNA = directly.=20 While most radiation-induced damage to DNA is repaired = by=20 mechanisms within the cell, double-strand breaks are = more=20 difficult to repair, and occasional misrepair can = result in=20 point mutations, chromosomal translocations, and gene = fusions,=20 all of which have the potential for induction of=20 cancer.¹⁰

Radiation-induced changes to neural tissue are now = known to=20 include visual deterioration, hearing loss, hormonal=20 disturbances, vasculopathy, brain and bone necrosis, = atrophy,=20 demyelination, calcification, fatty replacement of = bone=20 marrow, and induction of central nervous system=20 neoplasms,^3,55 and are=20 increasingly evident radiologically.⁵⁵ A dose=20 effect has been documented for many changes, including = tumor=20 induction.^{34,53,62,63,71,72}

Both x-rays and gamma rays are forms = of ionizing=20 radiation, which is defined as radiation that has = sufficient=20 energy to displace electrons from molecules. Free = electrons=20 can damage human cells. At very high doses, the damage = inflicted on tissues is evident within days of = exposure.=20 Late-onset effects such as cancer and other neoplasms, = however, may develop even with exposure to relatively = low=20 doses.

Radiation-Induced = Meningioma	AbstractIntroductionRadiation-Induced Meningi...=20 <<ConclusionsDisclaimerReferences

Radiation-induced meningioma is the most common = brain=20 neoplasm known to be caused by ionizing = radiation.^3,28 Harrison=20 et al.²⁴ grouped=20 RIMs into 3 categories: those due to high-dose (> = 20 Gy),=20 intermediate-dose (10=9620 Gy), and low-dose (< 10 = Gy)=20 radiation. Other authors define doses > 10 Gy as=20 high.^42,78

High-Dose RIMs=20

In 1953, Mann et al.³³=20 described a meningioma in a 4-year-old girl who had = undergone=20 radiation treatment for optic nerve glioma. The = child's=20 meningioma eventually became malignant. Several = authors have=20 summarized up to 126 cases of high-dose RIMs reported = in the=20 literature between 1953 and 2002.^{4,17,42,66,67,78,81} The=20 radiation doses ranged from 22 to 87 Gy, and the = majority of=20 patients had undergone radiotherapy as children. The = mean=20 latency from irradiation to diagnosis of the = meningioma was ~=20 19 years,^42,67 with a=20 tendency for shorter latency in patients treated with = higher=20 doses and those who had undergone radiotherapy at = younger=20 ages.^{2,17,24,32,42,78}

Low-Dose RIMs=20

The increased incidence of meningiomas following = exposure=20 to low-dose radiation has been reported in patients = who, as=20 children, had undergone radiation treatment for tinea = capitis,=20 those whose heads and necks were exposed to medical = and dental=20 x-rays at a young age, and survivors of the atomic = explosions=20 in Hiroshima and Nagasaki.

Irradiation for Tinea Capitis=20

Prior to the introduction of griseofulvin in = 1960,^18,27,60,82 the=20 world standard for treatment of tinea capitis was = scalp=20 irradiation.^5,7,22,59=20 Treatment for tinea capitis was administered using the = Adamson=96Keinbock technique, which was designed to = irradiate=20 the entire scalp as uniformly as possible through = exposure to=20 5 overlapping treatment areas.¹ = Phantom=20 studies using this technique showed that the radiation = dose to=20 the scalp was 5=968 Gy, the surface dose to the scalp = was 5=968=20 Gy, the surface dose to the brain was 1.4=961.5 Gy, = and the=20 skull base received an average of 0.7 Gy.⁵ = In 1966,=20 Albert et al.⁵ = reported a=20 substantial increase in cancer, mental disease, and = permanent=20 damage to scalp hair in 1908 patients in whom = radiotherapy was=20 performed for tinea capitis at the New York University = Medical=20 Center between 1940 and 1958, compared with 1801 = patients=20 treated for tinea capitis without radiotherapy during = the same=20 years. Other reports followed.^{7,20,24,41,59,76}

In 1974, Modan and colleagues³⁷ at the=20 Sheba Medical Center in Tel Aviv published a = retrospective=20 cohort study showing a significantly higher risk of = malignant=20 and benign head and neck tumors among ~ 11,000 Israeli = adults=20 treated for tinea capitis as children. This major=20 epidemiological work is widely credited as proving the = causal=20 role of radiation in the development of meningiomas in = some=20 patients. Follow-up studies of the Israeli cohort = showed that=20 a radiation dose of only 1=962 Gy administered during = childhood=20 led to a 9.5-fold increase in meningioma = incidence.⁵⁷=20 Continuing follow-up⁶³⁶⁵ shows that elevated risk = of brain=20 tumor, including meningioma, is positively associated = with=20 dose, with excess relative risk for benign meningioma = rising=20 to 18.82 for doses > 2.6 Gy.⁶³ These=20 studies showed a higher prevalence of calvarial tumors = and=20 multiple meningiomas, and higher recurrence rates in = RIMs than=20 SMs. The mean latency was ~ 36 years.

Low-Dose RIM Due to Dental Radiographic = Examination=20

In 1953, Nolan alone⁵⁰ and with=20 Patterson⁵¹=20 published studies in which significant blood changes = occurred=20 in patients exposed to 1.15=962.8 Gy during full-mouth = radiographic examinations. Nolan observed that = full-mouth=20 series delivered converging lines of radiation, with = high=20 points near the meninges. In 1980, nearly 30 years = later,=20 Preston-Martin et al.⁵⁴ noted a=20 higher incidence of meningioma in women with a history = of=20 full-mouth dental x-rays. The risk in this cohort = study was=20 higher in patients who had undergone radiographic = examinations=20 as children or teenagers and in those in whom = radiographic=20 examinations were conducted before 1945, when doses = were=20 higher. The majority of tumors were located in the = tentorial=20 or subtentorial region. The authors of more recent=20 case-control studies in Sweden⁵⁶ and the=20 US²⁹ have=20 found that dental radiographic examinations performed = during=20 the adult years may also increase the risk of=20 meningioma.

Radiation-Induced Meningiomas in = Survivors of=20 Atomic Bombs Dropped on Hiroshima and Nagasaki=20

The increased incidence of meningiomas = among=20 survivors of the 1945 atomic explosions in Japan was = shown=20 only in 1994, when Shibata et al.⁷⁰=20 demonstrated a higher incidence of meningiomas in = survivors of=20 the bombing in Nagasaki. In 1997 Shintani et = al.^71,72=20 published similar findings after studying data = obtained in=20 Hiroshima survivors. Due to the relatively low-dose = exposure=20 to ionizing radiation among these survivors compared = with=20 those undergoing radiotherapy for tinea capitis, the = average=20 latency was greater in the Japanese studies. The risk = of=20 meningioma induction was shown to increase with closer = proximity to the bombs' epicenters and in those = exposed during=20 childhood.⁵³

Clinical = Presentation	AbstractIntroductionRadiation-Induced = Meningi...Clinical Presentation=20 <<ConclusionsDisclaimerReferences

Radiation-induced meningiomas typically display = female=20 preponderance, although the difference between sexes = may be=20 less distinct compared with SMs.^{32,42,53,56,64,67,80} Strojan=20 et al.⁷⁸ reported=20 female predominance of 1.33:1 in a survey of 126 cases = of=20 high-dose RIMs. In a review of the incidence of = central=20 nervous system tumors among survivors of the atomic = bombs in=20 Hiroshima and Nagasaki, Preston et al.⁵³ found=20 that excess relative risk for RIMs is higher in men = than in=20 women.

Scanty hair, or alopecia, and an atrophic scalp are = hallmarks of irradiation.^24,55,59,73 We are=20 also of the impression that microcephaly is increased = in=20 patients with low-dose RIMs compared with the general=20 population, although no evidence has been reported in = the=20 literature. Microcephaly most likely results from = premature=20 closure of the skull sutures when radiation is = administered to=20 the head in young children.

The location of the RIM is primarily related to the = site of=20 exposure. The authors of several large studies = conducted in=20 Israel have documented a primarily calvarial location = in=20 patients treated for tinea capitis.^59,64,75 Ghim et=20 al.¹⁷ found=20 that 11 of 13 pediatric patients with high-dose RIMs = had=20 calvarial meningiomas, whereas skull base meningiomas = were=20 found in 4=9619% of patients with RIM in whom there = was a=20 history of high-dose irradiation for primary brain=20 tumors.^39,59,67,76=20 Epidemiological studies of patients with RIM linked to = full-mouth dental x-rays have shown that skull base=20 meningiomas are more common following this type of = radiation=20 exposure.⁵⁴

The latency period between exposure and clinical = diagnosis=20 of meningioma varies with radiation dose and age at = initial=20 treatment. Sadetzki et al.⁶⁴ reported=20 a 36.3-year average latency (range 12=9649 years) in = the Israeli=20 low-dose cohort study. In a thorough review of the = literature,=20 Harrison et al.²⁴=20 calculated that a mean of 35.2 years elapsed between = low-dose=20 irradiation (< 10 Gy) and diagnosis, whereas a mean = of 26.1=20 and 19.5 years, respectively, elapsed in patients = receiving=20 moderate (10=9620 Gy) and high-dose (> 20 Gy) = treatment. In=20 their survey of reported cases of RIM in patients = exposed to=20 high-dose radiation, Strojan et al.⁷⁸ observed=20 average latency of 18.7 years and also noted shorter = latency=20 in patients in whom radiation treatments were = administered at=20 younger ages. Ghim et al.¹⁷ found a=20 mean latency of only 10.8 years (range 5=9615.5) in a = study of=20 13 pediatric high-dose RIM patients with mean age at = diagnosis=20 13 years (range 6=9618). These patients had been = treated for=20 brain tumors at an average age of 2.5 years. A = 14-month=20 latency period was reported in an 11-year-old boy = following=20 high-dose irradiation for a tumor in the posterior=20 fossa.¹²

Radiation-induced meningioma differs from SM in = patient age=20 at presentation and in the multiplicity, = aggressiveness, and=20 rate of tumor recurrence. Mean age at presentation is = reported=20 as 29.2=9637.9 years in patients exposed to high-dose=20 radiation^{2,14,24,41,66,67,75} and=20 45=9658 years in those who received low-dose = treatment,^{2,24,52,59,76} whereas=20 SM generally arises in the 5th or 6th decade of = life.

The incidence of multiple lesions is elevated in = both=20 patients with low- and high-dose RIMs, and it ranges = from 4.6=20 to 18.7% of cases.^59,76=20 Multiplicity has been reported in 15.8% of patients = with RIMs,=20 compared with 2.4% of those with SMs in the Israeli = cohort=20 study.⁶⁴

Protocols for MR and CT imaging of RIM and SM are=20 comparable. The appearance of RIM on MR and CT images = is=20 comparable with SM; thus, the differential diagnosis = cannot be=20 based on imaging studies. The presence of multiple = meningiomas=20 in a patient with a history of head irradiation, as = well as=20 typical skin changes, raises the suspicion of RIM (Fig.=20 3).

View=20 larger version = (72K)

Fig. 3. = Multiplicity=20 is elevated in RIM.

Meningotheliomatous, transitional, and fibroblastic = histological subtypes are the most common in = RIM.^2,76=20 Histological features are distinctive compared with = SM. Soffer=20 et al.⁷⁶ have=20 noted high cellularity, nuclear pleomorphism, an = increased=20 mitotic rate, focal necrosis, bone invasion, and tumor = infiltration of the brain in a series of 42 patients = with=20 low-dose RIM. Rubinstein et al.⁵⁹ reported=20 several findings: a high degree of cellularity; = pleomorphic=20 nuclei with great variation in nuclear size, shape, = and=20 chromatin density; numerous multinucleated and giant = cells;=20 and nuclei with vacuolated inclusions. They also noted = frequent mitoses, psammoma bodies, foam cells, and = thickened=20 blood vessels that did not stain for amyloid. Louis et = al.³⁰ found=20 that RIMs were more often atypical, or aggressive and=20 multifocal, with higher proliferation indices than = SMs. Musa=20 et al.⁴² reported=20 a 23% incidence of atypia or malignancy among 79 cases = of=20 high-dose RIM.

Radiation-induced meningiomas may also exhibit more = aggressive clinical behavior than SMs,^{20,24,52,59,67,76}=20 including high recurrence rates following surgery and=20 radiotherapy. Rubinstein et al.⁵⁹ noted a=20 25.6% recurrence rate in 43 patients with RIM, and = 11.6% of=20 this group experienced multiple recurrences, compared = with an=20 11.4% recurrence rate in 258 patients with SMs in = their=20 series. Both groups were followed for only 4 years. = Higher=20 recurrence rates in patients with RIMs than those with = SMs=20 have also been reported elsewhere.^64,76

In a preliminary investigation, we = found=20 evidence of increased recurrence rates similar to = those seen=20 in other studies, but there was a significantly higher = rate of=20 multiplicity and much higher frequency of atypical = (WHO Grade=20 II) and anaplastic (WHO Grade III) histopathology in = patients=20 with RIMs compared with SMs treated in our institution = (F.=20 Umansky et al., unpublished data).

Management of RIM	AbstractIntroductionRadiation-Induced = Meningi...Clinical = PresentationManagement of RIM = <<ConclusionsDisclaimerReferences

Surgical Intervention=20

Surgical removal is the treatment of choice for = most cases=20 of RIM, although complete and safe resection may not = be=20 possible due to the lesion's frequent multiplicity,=20 involvement of osseous structures and vessels, and = aggressive=20 nature. Paradoxically, stereotactic radiosurgery or=20 fractionated stereotactic radiosurgery may be = appropriate=20 adjuncts to surgery or may be performed in lieu of = surgery in=20 some patients, despite the radiation-related origins = of RIMs.=20 In some patients, angiography may be appropriate for=20 visualization of the tumor's vascular anatomy and=20 pre-operative embolization.

The first consideration when planning the surgical = approach=20 for resection of RIM is often scalp atrophy, followed = by=20 multiplicity and the high rate of recurrence. The = scalp may be=20 slightly or severely atrophic and poorly vascularized, = depending on the radiation dose received. In some = patients,=20 the thickness of the entire galeal/skin flap may reach = only=20 1.5=962 mm, necessitating careful planning and = meticulous=20 technique to avoid cerebrospinal fluid leakage and = skin flap=20 dehiscence. The risk of these complications increases = in=20 patients with an atrophic scalp who require multiple=20 craniotomies, which is a common scenario in the RIM = population=20 (Fig.=20 4). In such cases, it may be appropriate to = include a=20 plastic surgeon on the team.

View=20 larger version = (153K)

Fig. 4. = Photograph of=20 a patient with an RIM and related alopecia = and=20 scalp atrophy.

A large percentage of RIMs are located at the = calvaria, and=20 in cases of parasagittal or falcine meningiomas = preoperative=20 assessment of the superior sagittal sinus is critical = in=20 planning surgery (Fig. 5). = We prefer=20 the use of MR imaging with MR venography for = assessment of=20 patency, although angiography may be required in rare = cases.=20 In patients with highly vascular tumors, preoperative=20 embolization may be beneficial.

View=20 larger version = (80K)

Fig. 5. = Studies=20 obtained in a 56-year-old woman who had = undergone=20 radiotherapy for tinea capitis at age 6 = years. A:=20 In recent years she had detected a growing = lump on=20 her scalp and had recently developed = difficulty=20 walking. B and C: Axial and sagittal CT = scans=20 revealed a large parasagittal meningioma. = Magnetic=20 resonance imaging had also shown an = additional=20 small, parasellar meningioma (data not = shown).=20 Note the presence of alopecia, a hallmark = of=20 radiation to the scalp.

If healthy skin is available at the periphery of = the=20 irradiated, atrophic scalp, it should be used.⁴² In our=20 experience, skin damage is often less severe in the = low=20 forehead, low temporal, or occipital areas compared = with the=20 convexity and vertex. When skin in these basal areas = is indeed=20 healthier and better vascularized, incisions may be = made more=20 inferiorly than usual. Use of hemostatic clamps or = coagulation=20 is not advised as they may further damage this fragile = skin=20 and may cause drying or shrinkage of the skin edges. = Straight=20 or slightly curved incisions are preferred to = horseshoe=20 contours, and flap size should be held to the = minimum.

Given the aggressive nature and high recurrence = rates of=20 RIMs, wide resection margins in the involved dura = mater are=20 vital.^8,9,26,74,80 In cases=20 in which the tumor involves under- or overlying bone, = the=20 osseous portion of the tumor should be radically=20 removed,^{24,59,76,77,80} because=20 osseous invasion has been linked to higher rates of = tumor=20 recurrence.^26,74 When we=20 find bone flap invasion or suspect it has occurred, we = autoclave the flap or replace it with acrylic graft.=20 Recurrence rates are higher among patients with tumors = involving the skull base or a major cranial sinus, = where wide=20 resection margins are often impossible to = achieve.^4,36,74

Fragile skin conditions frequently = necessitate=20 special considerations when closing the wound. = Multilayer=20 closure may be impossible, especially in convexity=20 meningiomas, since the atrophic scalp may not accept=20 additional sutures. In patients with a very thin = scalp, we=20 close the skin and galea aponeurosis with a single = layer of=20 running 3-0 sutures, with or without locking, using = nylon, not=20 Vicryl. This closure should be performed carefully to = provide=20 a single, watertight layer, capable of preventing=20 cerebrospinal fluid leakage; however, if the stitches = are=20 closed too tightly, skin necrosis may result and cause = potentially serious consequences. Staples are not = suitable for=20 closure in these patients. They provide poor = approximation,=20 without hermetic closure, and can easily damage a = fragile,=20 atrophic scalp.

Stereotactic Radiosurgery and = Fractionated=20 Stereotactic Radiotherapy=20

Surgery may be followed by = radiotherapy in=20 patients with RIMs if radical excision cannot be = achieved.=20 When patients have already received the maximum = tolerable dose=20 of radiation, stereotactic radiotherapy or = stereotactic=20 radiosurgery may be preferable to conventional = radiotherapy.=20 Adjuvant conventional conformal radiation is generally = recommended following surgery or radiosurgery to treat = viable=20 tumor cells that remain along the dura and in brain = parenchyma=20 in patients with atypical (WHO Grade II), anaplastic = (WHO=20 Grade III), or malignant (WHO Grade IV) = meningiomas.^8,9,80 Careful=20 consideration should be given to original doses and = treatment=20 fields when planning new therapeutic = irradiation.

Other Therapies=20

Systemic treatment with = tamoxifen²¹ and=20 hydroxyurea^{35,4749,58,68,69} has been=20 attempted as an adjuvant therapy in patients with = recurrent,=20 unresectable SMs. In the past, we have used both of = these=20 agents in selected RIM patients with recurrent tumors = when=20 surgery and radiotherapy failed, with no measureable = response.=20 In our experience, these agents did not provide = measurable=20 clinical benefit for the management of=20 meningioma.

Conclusions	AbstractIntroductionRadiation-Induced = Meningi...Clinical = PresentationManagement of RIMConclusions = <<DisclaimerReferences

Exposure to ionizing radiation has been shown to=20 significantly increase the risk of meningioma, a solid = tumor=20 arising from cells of the meningeal coverings of the = brain.=20 The risk of meningioma formation increases, and the = latency=20 period between exposure and tumor development = decreases, with=20 higher doses of radiation; however, exposure to even = low=20 radiation doses has been shown to significantly = increase the=20 risk of meningioma.^53,62,6972

The Israeli experience has shown that even low-dose = radiation in children leads to a high and significant = increase=20 in the risk of developing meningioma. This risk should = be=20 considered when decisions are made to use radiation in = routine=20 imaging examinations, such as CT scanning,¹⁰ or to=20 administer higher doses of radiation for treatment of = benign=20 tumors during childhood, adolescence, and young=20 adulthood.^{24,17,42,78,81}

Radiation-induced meningiomas are = characterized=20 by marked changes to the scalp, including alopecia, = atrophy,=20 and poor vascularization. Patients with RIMs = frequently=20 present with multiple tumors. Compared with SMs, a = higher=20 proportion of RIMs are atypical or anaplastic, and = recurrence=20 rates are higher. Poor skin condition may necessitate=20 adjustment of the surgical approach and skin flap = placement.=20 Paradoxically, stereotactic radiotherapy may be used = to treat=20 patients with unresectable or residual/recurrent=20 tumors.

Disclaimer	AbstractIntroductionRadiation-Induced = Meningi...Clinical = PresentationManagement of RIMConclusionsDisclaimer <<

The authors did not receive outside = support for=20 research or preparation of this article. Furthermore, = the=20 authors have no conflicts of interest relating to = companies=20 mentioned or relevant to its subject.

References	AbstractIntroductionRadiation-Induced = Meningi...Clinical = PresentationManagement of RIMConclusionsDisclaimerReferences = <<

1.	Adamson H: A simplified = method of x-ray=20 application for the cure of ringworm of the = scalp:=20 Keinbock's method. Lancet = 1:1378=961380,=20 1909
2.	Al-Mefty O, Kadri PA, = Pravdenkova = S,=20 = Sawyer=20 JR, =20 Stangeby C, Husain M: = Malignant = progression in=20 meningioma: documentation of a series and = analysis of=20 cytogenetic findings. J = Neurosurg=20 101:210=96218, 2004
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