Adjuvant radiotherapy for atypical meningiomas

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OBJECTIVE

The aim of this paper was to evaluate outcomes in patients with atypical meningiomas (AMs) treated with surgery alone compared with surgery and radiotherapy at initial diagnosis, or at the time of first recurrence.

METHODS

Patients with pathologically confirmed AMs treated at the University of Utah from 1991 to 2014 were retrospectively reviewed. Local control (LC), overall survival (OS), Karnofsky Performance Status (KPS), and toxicity were assessed. Outcomes for patients receiving adjuvant radiotherapy were compared with those for patients treated with surgery alone. Kaplan-Meier and the log-rank test for significance were used for LC and OS analyses.

RESULTS

Fifty-nine patients with 63 tumors were reviewed. Fifty-two patients were alive at the time of analysis with a median follow-up of 42 months. LC for all tumors was 57% with a median time to local failure (TTLF) of 48 months. The median TTLF following surgery and radiotherapy was 180 months, compared with 46 months following surgery alone (p = 0.02). Excluding Simpson Grade IV (subtotal) resections, there remained an LC benefit with the addition of radiotherapy for Simpson Grade I, II, and III resected tumors (median TTLF 180 months after surgery and radiotherapy compared with 46 months with surgery alone [p = 0.002]). Patients treated at first recurrence following any initial therapy (either surgery alone or surgery and adjuvant radiotherapy) had a median TTLF of 26 months compared with 48 months for tumors treated at first diagnosis (p = 0.007). There were 2 Grade 3 toxicities and 1 Grade 4 toxicity associated with radiotherapy.

CONCLUSIONS

Adjuvant radiotherapy improves LC for AMs. The addition of adjuvant radiotherapy following even a Simpson Grade I, II, or III resection was found to confer an LC benefit. Recurrent disease is difficult to control, underscoring the importance of aggressive initial treatment.

ABBREVIATIONS AM = atypical meningioma; CTCAE = Common Terminology Criteria for Adverse Events; EOR = extent of resection; GTR = gross-total resection; KPS = Karnofsky Performance Status; LC = local control; LF = local failure; OS = overall survival; PFS = progression-free survival; SRS = stereotactic radiosurgery; STR = subtotal resection; TTLF = time to local failure.

Abstract

OBJECTIVE

The aim of this paper was to evaluate outcomes in patients with atypical meningiomas (AMs) treated with surgery alone compared with surgery and radiotherapy at initial diagnosis, or at the time of first recurrence.

METHODS

Patients with pathologically confirmed AMs treated at the University of Utah from 1991 to 2014 were retrospectively reviewed. Local control (LC), overall survival (OS), Karnofsky Performance Status (KPS), and toxicity were assessed. Outcomes for patients receiving adjuvant radiotherapy were compared with those for patients treated with surgery alone. Kaplan-Meier and the log-rank test for significance were used for LC and OS analyses.

RESULTS

Fifty-nine patients with 63 tumors were reviewed. Fifty-two patients were alive at the time of analysis with a median follow-up of 42 months. LC for all tumors was 57% with a median time to local failure (TTLF) of 48 months. The median TTLF following surgery and radiotherapy was 180 months, compared with 46 months following surgery alone (p = 0.02). Excluding Simpson Grade IV (subtotal) resections, there remained an LC benefit with the addition of radiotherapy for Simpson Grade I, II, and III resected tumors (median TTLF 180 months after surgery and radiotherapy compared with 46 months with surgery alone [p = 0.002]). Patients treated at first recurrence following any initial therapy (either surgery alone or surgery and adjuvant radiotherapy) had a median TTLF of 26 months compared with 48 months for tumors treated at first diagnosis (p = 0.007). There were 2 Grade 3 toxicities and 1 Grade 4 toxicity associated with radiotherapy.

CONCLUSIONS

Adjuvant radiotherapy improves LC for AMs. The addition of adjuvant radiotherapy following even a Simpson Grade I, II, or III resection was found to confer an LC benefit. Recurrent disease is difficult to control, underscoring the importance of aggressive initial treatment.

Meningiomas are the most commonly diagnosed primary brain tumors in adults,11 accounting for approximately one-third of these tumors.20 The incidence is increasing in the United States,4 and from 2004 to 2011 the average annual incidence was 7.6 per 100,000 persons.4 Meningiomas are thought to arise from arachnoidal cap cells in the meninges that surround the central nervous system.20 The WHO classifies meningiomas into 3 groups that predict tumor behavior: benign (WHO Grade I), atypical (WHO Grade II), and anaplastic or malignant (WHO Grade III).20 While patients diagnosed with benign meningiomas have excellent outcomes,6 atypical and malignant meningiomas are aggressive and portend a worse prognosis.7,10,11,17,20 In 2000, the WHO altered the definition of atypical meningioma (AM);2,20 retrospective data suggest that patients harboring these tumors have better outcomes than those with malignant pathology.16 These revised criteria persist in the most recent edition of the WHO Classification of Tumors of the Central Nervous System, published in 2007.18 Currently, AMs account for approximately 15%–20% of all meningiomas diagnosed. They are defined by the WHO as meeting one of the following criteria: mitotic index greater than or equal to 4 mitoses per 10 hpf, or exhibiting 3 or more of the following histological features: increased cellularity, small cells with a high nuclear-to-cytoplasmic ratio, prominent nucleoli, uninterrupted patternless or sheet-like growth, or foci of spontaneous necrosis.18 Given more recent changes in the histopathological definition of AMs, optimal treatment and outcome data for this group of patients are lacking. Consensus guidelines regarding recommendations for patients whose tumors display an atypical pathology are not definitive, suggesting that postoperative radiotherapy can be considered in appropriate cases (https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site). Retrospective data from single institutions suggest that adjuvant radiotherapy may be beneficial,2,11,12,19,24,25 and a Phase II trial to further delineate optimal treatment is ongoing (https://clinicaltrials.gov/ct2/show/NCT00895622). To investigate the role of adjuvant radiotherapy in this population, we identified all patients treated at our institution for AM as defined by the 2007 WHO criteria, comparing outcomes of patients treated with combined modality therapy (surgery followed by radiotherapy) to those treated with a single modality (surgery alone).

Methods

A retrospective review of all patients with a diagnosis of AM treated between 1991 and 2014 was performed. Patients treated prior to 2007 underwent central pathology review to confirm that they met the 2007 criteria.13,18 Assessed variables included age at diagnosis, sex, extent of resection as determined according to the Simpson grading system by a neurosurgeon, adjuvant radiotherapy, and treatment parameters. Primary outcome measures were local control (LC), time to local failure (TTLF), and overall survival (OS). Extent of resection (EOR) was defined by the Simpson grading system21 based on the operative report and postoperative images. Radiotherapy treatment parameters included whether adjuvant radiotherapy was administered in the postoperative setting, whether radiotherapy was delivered as a fractionated course or in a single fraction, and total dose administered. A separate analysis was performed in patients for whom initial treatment for an AM failed or those whose tumors recurred. Assessed variables were identical to those discussed above. The records of deceased patients were examined in further detail to determine cause of death.

Patients treated with radiotherapy underwent pretreatment imaging using high-resolution MRI with a 3D spoiled gradient–recalled T1-weighted image with gadolinium contrast administration. A noncontrast CT scan was obtained for radiotherapy planning, with the patient in a thermoplastic mask for immobilization. MR and CT images were fused, and target volumes and organs at risk were delineated on the MR images using BrainSCAN or iPlan software (Brainlab). The operative bed and/or intact meningioma was contoured, and in a postoperative case a 5-mm clinical target volume margin was added. An additional 3- to 5-mm margin was added to account for daily setup and alignment error when using a fractionated treatment plan, although with radiosurgery no planning target volume margin was added, as is our institutional standard. Treatment planning was completed to optimize tumor coverage while sparing the dose to structures at risk. Typical dose constraints for a fractionated treatment course included a maximum of 54 Gy to the optic structures, 45 Gy to the retinas, 7 Gy to the lenses, 54 Gy to the brainstem, and 45 Gy to the spinal cord. Dose constraints for radiosurgery included a maximum of 8 Gy to the optic structures and 15 Gy to the brainstem.

Local failure (LF) was defined as new evidence of tumor in the resection cavity or an increase in linear tumor size of 25% or more for intact tumors as measured by the maximal linear dimension. MRI (CT was used for 1 patient only) and clinical follow-up notes were reviewed to define LF or LC and when it occurred and Karnofsky Performance Status (KPS) before and after treatment, as well as toxicity information using the Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Vital status, defined as the patient's date of death or last followup appointment/last contact according to the electronic medical record, was used to calculate overall survival. Estimates of LC, TTLF, and OS were calculated from the date of completion of initial treatment, either resection or the day the patient completed radiotherapy if adjuvant radiotherapy was administered, using the Kaplan-Meier method with log-rank test for significance. The t-test was used for continuous variables; the chi-square and Fisher's exact tests were used for categorical variables. Significance was defined as p < 0.05. The University of Utah Institutional Review Board approved this retrospective review.

Results

Treatment at Time of Initial Diagnosis

Fifty-nine patients treated at our institution for 63 resected AMs were identified; demographics and tumor characteristics are shown in Tables 1 and 2. Thirty-three percent of tumors were treated with surgery followed by adjuvant radiotherapy, and 67% were treated with surgery alone. The majority of patients had a KPS of 70 or greater, and there was no difference in KPS between the patients treated with surgery alone and those treated with surgery plus radiotherapy. At last follow-up the majority of patients had a KPS of 70 or greater (Table 1). Of those 21 tumors treated with adjuvant radiotherapy, the majority (86%) were treated with fractionated radiation therapy with a median dose of 54 Gy (range 45–59.4 Gy). The remaining 3 tumors were treated using stereotactic radiosurgery (SRS) with a median dose of 15 Gy (range 12.5–15 Gy). SRS was used in these patients due to small-volume disease, and, in a single case, in the setting of a second meningioma in a different location. Of the 63 tumors (treated with either surgery or surgery plus radiotherapy), 57% were controlled at the time of analysis with a median follow-up of 26 months (range 3–111 months). Figure 1 displays LC for all AMs, with a median TTLF of 48 months.

TABLE 1.

Patient and treatment demographics

VariableAll Patients (%)Surgery Alone (%)Surgery & Adjuvant RT (%)p Value
Median age in yrs5354520.7
Sex0.8
  Male28/59 (47)20/42 (48)7/17 (41)
  Female31/59 (53)22/42 (52)10/17 (59)
KPS0.8
  Initial
    1005 (8)3 (7)2 (12)
    9016 (27)11 (26)5 (29)
    8022 (37)15 (36)7 (41)
    7012 (20)10 (24)2 (12)
    601 (2)1 (2)0
    502 (3)1 (2)1 (6)
    401 (2)1 (2)0
    30000
    20000
  Last follow-up
    10020 (34)
    9013 (22)
    8015 (25)
    703 (5)
    602 (3)
    502 (3)
    400
    300
    201 (2)
    NA3 (5)

FRT = fractionated radiotherapy; NA = not available; RT = radiotherapy.

TABLE 2.

Tumor characteristics

VariableAll Meningiomas (%)Surgery Alone (%)Surgery & Adjuvant RT (%)p Value
Simpson grade (EOR)0.0003
  I47/63 (75)37/47 (79)10/47 (21)
  II3/63 (5)2/3 (67)1/3 (33)
  III2/63 (3)1/2 (50)1/2 (50)
  IV11/63 (17)2/11 (18)9/11 (17)
Location
  Parasagittal10/63 (16)
  Convexity27/63 (43)
  Sphenoid ridge6/63 (10)
  Suprasellar4/63 (6)
  Posterior fossa6/63 (10)
  Olfactory groove6/63 (6)
  Middle fossa1/63 (2)
  Cerebellopontine angle3/63 (5)
  Periventricular2/63 (3)
Adjuvant RT
  Yes21/63 (33)
    FRT18/21 (86)
    SRS3/21 (14)
  No42/63 (67)

A total of 59 patients with 63 meningiomas were reviewed.

FIG. 1.
FIG. 1.

LC for all treated AMs. The median time to local failure was 48 months.

LC was then examined for treated tumors stratified by initial treatment of either surgery alone or surgery plus radiotherapy (Table 3). The median TTLF for those treated with surgery plus radiotherapy was 180 months, compared with 46 months for those treated with surgery alone (p = 0.02), as shown in Fig. 2.

TABLE 3.

Outcomes by EOR and initial treatment

OutcomeAny SG & RT (%)Any SG (%)SG I–III & RT (%)SG I–III (%)SG IV & RT (%)SG IV (%)
Controlled16 (76)20 (48)11 (92)20 (50)4 (56)0
Failed5 (24)22 (52)1 (8)20 (50)5 (50)2 (100)
Total2142124092

SG = Simpson grade.

FIG. 2.
FIG. 2.

LC for all treated AMs, stratified by initial treatment with surgery alone (S) compared with surgery and radiotherapy (S/RT). The median time to LF following surgery plus radiotherapy was significantly longer at 180 months compared with 46 months following surgery alone (p = 0.02).

EOR was defined for each tumor according to the Simpson grading system. Simpson Grade I, II, or III resection was obtained in 83% (Table 1), and the majority of these tumors (77%) were treated with surgery alone in the upfront setting, with no adjuvant radiotherapy. LC following surgery plus radiotherapy was excellent, at 92%, whereas following surgery alone LC was 50% (Table 3). Those who received surgery plus radiotherapy had a significantly better median TTLF of 180 months with only a single failure, compared with a median TTLF of 46 months following surgery alone (p = 0.002, Fig. 3). Simpson Grade IV resection was obtained in 17% of all AMs, and of these, 82% were treated with adjuvant radiotherapy. No tumors treated with Simpson Grade IV resection alone were controlled, whereas 56% of those receiving postoperative radiotherapy were controlled, although there was no significant difference in median TTLF between these groups (p = 0.41). Of those tumors controlled with postoperative radiotherapy, all had stable disease at follow-up with no significant regression appreciated.

TABLE 4.

Outcomes after salvage treatment following recurrence

OutcomeSalvage Treatment (%)
Surgery & RTRTSurgeryTotal
Controlled1 (25)3 (25)1 (10)5 (19)
Failed3 (75)9 (75)9 (90)21 (81)
Total4121026
FIG. 3.
FIG. 3.

LC for AMs treated with a Simpson Grade I, II, or III resection, stratified by initial treatment with surgery alone compared with surgery and radiotherapy. The median time to LF following surgery plus radiotherapy was significantly longer at 180 months (with only a single failure) compared with 46 months following surgery alone (p = 0.002).

At the time of analysis, 52 patients (88%) were alive. OS was not affected by initial treatment modality, EOR, or LC following initial management. Of the 7 patients who died, 4 were treated with surgery alone upfront (3 with a Simpson Grade I resection and 1 with a Simpson Grade III resection) and 3 with surgery plus radiotherapy (all following a Simpson Grade IV resection). Only one patient's tumor was controlled initially; upfront management failed in the remaining patients. The cause of death varied: 1 patient had multiple tumors at presentation; 1 developed metastatic disease to the spine; and 2 patients developed multiply recurrent disease, were treated multiple times with surgery and radiation therapy, and were known to die of their disease. One patient died after complications following anesthesia after craniotomy, another patient died of heart disease, and another died of unknown causes.

Treatment at Time of Recurrence

The 26 patients in whom initial treatment failed were analyzed separately (Table 4). Initial treatment for 23 of these 26 patients was surgery alone; only 3 patients received adjuvant radiotherapy. Following first LF, 4 were treated with surgery plus radiotherapy, 12 with radiotherapy alone, and 10 with surgery alone. The first salvage treatment failed in the majority of these patients (81%), with a median TTLF after first salvage therapy of 26 months. There was no significant difference in LC when stratified by type of salvage therapy (p = 0.87). LC was obtained in only 1 of 4 patients treated with surgery plus radiotherapy, 3 of 12 treated with radiotherapy alone, and 1 of 10 treated with surgery alone. LC after salvage was not significantly improved with the addition of radiotherapy, with a median TTLF of 25 months when salvage included radiotherapy (either radiotherapy alone or surgery plus radiotherapy), compared with 35 months when salvage was surgery alone (p = 0.96). Half of the patients who were treated with salvage radiotherapy received fractionated radiotherapy and half received SRS, with no difference in LC (p = 0.26).

LC for tumors treated at initial diagnosis was significantly better than LC for tumors treated at first recurrence with any treatment modality. The median TTLF for tumors treated at initial diagnosis was 48 months, compared with 26 months for those treated at first recurrence (p = 0.007, Fig. 4). There was no OS difference between patients treated at initial diagnosis compared with those treated at first salvage; the median time to death for patients treated after failure of initial therapy was 185 months, and this end point was not reached in the group of patients treated at initial diagnosis (p = 0.5).

FIG. 4.
FIG. 4.

LC for all AMs treated at initial diagnosis compared with at first salvage. The median time to LF for those tumors treated at initial diagnosis was 48 months, significantly longer than for those treated at first salvage, which was 26 months (p = 0.007).

Toxicity

The CTCAE grading scale was used to capture the most severe toxicity information attributed to treatment modality, surgery or radiotherapy. As shown in Table 5, there were no Grade 5 toxicities attributed to either surgery or radiotherapy. One patient developed a Grade 4 optic nerve disorder attributed to both surgery and radiotherapy. Of those patients who developed Grade 3 toxicities, 1 had undergone surgery and radiotherapy and developed meningiomatosis and had also suffered a stroke; therefore, it was difficult to determine whether the Grade 3 toxicities reported were related to treatment, disease progression, or stroke. The other Grade 3 toxicity after radiotherapy occurred in a patient who suffered radiation necrosis. Grade 3 toxicities related to surgery included optic nerve disorder, wound infection, cognitive disturbance, hematoma, and wound infection. Grade 2 toxicities related to radiotherapy included headache, alopecia, dizziness, and hearing and memory impairment in patients who underwent both surgery and radiotherapy. Grade 2 toxicities related to surgery included headache, confusion, memory impairment, cognitive disturbance, wound infection, gait disturbance, muscle weakness, cranial nerve toxicities, paresthesias, seizure, and CSF leakage. Grade 1 radiation-related toxicities included fatigue, headache, and seizure in a patient who underwent surgery and radiotherapy. Grade 1 surgery-related toxicities included cognitive disturbance, seizure, and dysesthesias. Toxicity at last follow-up was also captured and 49 patients had no reported toxicity attributed to treatment, 7 had a Grade 1 toxicity, and 3 did not have documentation either way. The Grade 1 toxicities included cognitive decline, radiation necrosis, fatigue, postoperative infection, steroid use, “clinical dementia syndrome” as diagnosed by a neurologist, and alopecia.

TABLE 5.

CTCAE toxicity

CTCAE Toxicity GradeSurgery-Related Toxicity (%)RT-Related Toxicity (%)Last Follow-Up (%)
NA3 (5)23 (39)3 (5)
031 (53)25 (42)49 (83)
13 (5)4 (7)7 (12)
215 (25)4 (7)0
36 (10)2 (3)0
41 (2)1 (2)0
5000

Any documented toxicity.

Discussion

AMs have aggressive histological features, including high mitotic indices and necrosis,20 and retrospective data show a poor prognosis with this diagnosis compared with benign meningiomas.7,10,11,17 Progression-free survival (PFS) is poor, with retrospective data showing PFS of 38%–59% at 5 years,5,9,10 and 19%–22% at 8–10 years.5,10 Patients with AMs have a much shorter median OS compared with those with benign meningiomas.10,16,19 Due to the fact that older retrospective studies group AMs and malignant meningiomas together, many of the data do not reflect outcomes for patients with solely atypical histology.15 More recently, investigators have attempted to define outcomes for this group separately, indicating that these patients have better outcomes—and should be classified separately—than those with malignant histology.16 The updated pathological definition of AMs published in 2007 by the WHO13,18 provides more specific criteria for diagnosis, differentiating these patients from those with malignant disease. Thus, this group of patients can now be specifically examined to define the clinical characteristics and behavior of this tumor.

The routine use of adjuvant radiotherapy following resection of AMs is controversial because although some series demonstrate that the addition of radiotherapy is an independent predictor of improved PFS,17,19,23 others dispute this finding and recommend against the routine use of adjuvant radiotherapy.3,14,23 One retrospective study, examining 108 patients with AM and gross-total resection (GTR), showed 100% LC in 8 patients with the addition of adjuvant radiotherapy, compared with a 48% recurrence rate at 10 years after GTR alone.2 The authors encouraged immediate postoperative radiotherapy for patients with AM, irrespective of the EOR.2 Similarly, other retrospective data identify LC of 92% in 13 patients with AM treated with GTR and radiotherapy, whereas LC was only 59% with GTR alone.12 One large single-institution study examined more than 200 patients with AM, and for those with GTR, LC was 100% when treated with adjuvant radiotherapy, either SRS or fractionated radiotherapy. However, there were only 16 patients total in this group, and the LC benefit was not significant compared with GTR alone;8 therefore, these authors argue that observation following GTR is a reasonable approach. A recent study from Taiwan examining 28 patients with skull base AMs reported 100% LC in 3 patients after GTR and adjuvant radiotherapy, as well as an LC benefit with the addition of radiotherapy following subtotal resection (STR).25 A retrospective review of 75 patients with AM and 13 patients with malignant meningioma also showed a significant improvement in OS with the addition of radiotherapy.19 It is clear that prospective studies and randomized data are necessary to confirm these findings, as population-based studies have not clearly defined optimal treatment strategies.22 Retrospective studies provide an important perspective on outcomes, helping guide treatment decision making while we await 2 ongoing studies that are currently enrolling patients.

Our data demonstrate an improvement in LC outcomes with the addition of radiotherapy after Simpson Grade I, II, or III resection, although no OS benefit was shown. Specifically, following a Simpson Grade I, II, or III resection, surgery plus radiotherapy failed in only 1 of 12 (8.3%) as opposed to surgery alone failing in 20 of 40 patients (50%). These findings support those of other retrospective reviews, providing additional data demonstrating the utility of adjuvant radiotherapy in providing an LC benefit after a Simpson Grade I, II, or III resection. In contrast to other studies, we did not show a statistically significant improvement in LC with the addition of radiotherapy following a subtotal (Simpson Grade IV) resection. This could be explained by the fact that only 11 tumors in our study were treated with a Simpson Grade IV resection, as opposed to 52 treated with a Simpson Grade I, II, or III resection. OS was not affected by type of initial therapy, EOR, or LC, which is consistent with other series.

LC following recurrence is difficult to attain, and outcomes are generally worse for these patients, with a reported 10-year OS of only 69%.2 There is no standard treatment paradigm for salvage therapy, and the patients are managed with surgery or radiotherapy alone or in combination. A recent publication from France that included 27 patients treated for recurrent AM with SRS reported a 1-year LC of 75%, but only 40% at 3 years, with regional control of 75% and 33% at these time periods, respectively.1 Another retrospective study of atypical and malignant meningiomas treated at recurrence with radiotherapy showed a significant benefit in PFS compared with those managed without radiotherapy,19 although a separate series demonstrated that SRS had less efficacy when patients had multiple failures prior to treatment with SRS.3 It remains unclear whether SRS or fractionated radiotherapy is superior in the salvage setting. One of the largest single-institution studies did not show a difference, although numbers were small.8 Our series demonstrates poor outcomes after salvage treatment, with a median TTLF of 26 months and a median time to death of 186 months. These patients had a significantly shorter interval between first salvage therapy and failure when compared with patients treated at initial diagnosis. These poor outcomes demonstrate the importance of controlling disease at diagnosis.

This study is limited in that it is a retrospective review of patients treated at a single institution. The use of adjuvant radiotherapy was not studied in a prospective manner, but at the discretion of the treating physician. Due to the retrospective nature of this study, the use of adjuvant radiotherapy could have been biased and given more often to patients with a suboptimal resection; however, we would expect this selection bias to skew the results in favor of surgery alone. Historically, adjuvant radiotherapy was recommended more often for AMs following STR at our institution. Currently, it is recommended that all patients with AM receive adjuvant radiotherapy, irrespective of EOR. Additionally, radiotherapy dose recommendations have changed over the time course of this study. We currently recommend fractionated radiotherapy doses of 54 Gy or 59.4 Gy following GTR or STR, respectively, and SRS doses of 18–20 Gy, usually in the setting of multiple or recurrent tumors. Strengths of this study include a relatively large sample size compared with what has been published in the literature, as well as in-house review of all pathology specimens to confirm the atypical histology for all patients included in this analysis.

Conclusions

Standard management of AMs has yet to be defined. While it is widely accepted that EOR plays an important role, adjuvant radiotherapy is controversial. Our data support the use of upfront adjuvant radiotherapy following even a Simpson Grade I, II, or III resection. Aggressive initial management should be offered to all patients, as failure is difficult to salvage and the interval between treatment and subsequent failure becomes significantly shorter.

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Disclosures

Dr. Jensen reports that he is a consultant for Medtronic, Varian, and Pharmaco-Kinesis.

Author Contributions

Conception and design: Shrieve, Bagshaw, Jensen, Palmer. Acquisition of data: Bagshaw, Burt, Jensen, Palmer. Analysis and interpretation of data: Shrieve, Bagshaw, Jensen, Suneja. Drafting the article: Shrieve, Bagshaw, Jensen, Suneja, Palmer, Couldwell. Critically revising the article: Shrieve, Burt, Jensen, Suneja, Palmer, Couldwell. Reviewed submitted version of manuscript: Shrieve. Approved the final version of the manuscript on behalf of all authors: Shrieve. Statistical analysis: Shrieve, Bagshaw. Administrative/technical/material support: Shrieve. Study supervision: Shrieve.

Supplemental Information

Previous Presentations

This paper was presented orally at the 57th Annual Meeting of the American Society for Radiation Oncology, October 18–21, 2015, San Antonio, Texas, and it was presented at the “Best of ASTRO” meeting November 13–14, 2015, San Diego, California.

Article Information

INCLUDE WHEN CITING Published online September 9, 2016; DOI: 10.3171/2016.5.JNS152809.

Correspondence Dennis C. Shrieve, Department of Radiation Oncology, University of Utah, Huntsman Cancer Institute, 1950 Circle of Hope, Rm. 1570, Salt Lake City, UT 84112. email: dennis.shrieve@hci.utah.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    LC for all treated AMs. The median time to local failure was 48 months.

  • View in gallery

    LC for all treated AMs, stratified by initial treatment with surgery alone (S) compared with surgery and radiotherapy (S/RT). The median time to LF following surgery plus radiotherapy was significantly longer at 180 months compared with 46 months following surgery alone (p = 0.02).

  • View in gallery

    LC for AMs treated with a Simpson Grade I, II, or III resection, stratified by initial treatment with surgery alone compared with surgery and radiotherapy. The median time to LF following surgery plus radiotherapy was significantly longer at 180 months (with only a single failure) compared with 46 months following surgery alone (p = 0.002).

  • View in gallery

    LC for all AMs treated at initial diagnosis compared with at first salvage. The median time to LF for those tumors treated at initial diagnosis was 48 months, significantly longer than for those treated at first salvage, which was 26 months (p = 0.007).

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