distinguishing grade 1 meningioma from higher grade meningiomas without biopsy

2
looked for ongoing trials at clinicaltrials.gov and controlled-trials.com. Referenced studies cited in published guidelines for prostate cancer as well as in reviews and other relevant articles identified in the search were also assessed for eligibility. The systematic review was conducted following a pre-established protocol. RCTs comparing intermittent (IAD) versus continuous (CAD) androgen deprivation therapy (any regimen) for patients with prostate cancer (any stage) were considered eligible. Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival (biochemical and/or clinical), time to castration resistance, skeletal-related events and side effects. Duration of off-treatment inter- vals and testosterone levels were also considered for the IAD group. Two reviewers performed study selection, data abstraction and risk of bias assessment, independently. Hazard ratios using random effect models were conducted with generalized inverse variance method. Heterogeneity was assessed using I2 statistic. Results: Among 8280 references, 14 studies were eligible. All studies presented an unclear or high risk of bias for the two primary outcomes. There was no significant difference between IAD and CAD in terms of overall survival (HR 1.02, 95% CI: 0.93-1.13; 5 studies, 4239 patients), cancer-specific survival (HR 1.00, 95% CI: 0.76-1.32; 3 studies, 1318 patients), and progression-free survival (HR 0.95, 95% CI: 0.78-1.14; 4 studies, 2704 patients). In 10 trials providing data on quality of life, 8 used different version of the EORTC QLQ-C30 questionnaire and 2 used other questionnaires. These studies observed variable results. No difference between the two interventions was observed for hot flashes, gynecomastia, depression, erectile dysfunction, decreased libido, and cardiovascular death. Conclusions: In our systematic review, we did not observe a difference in overall survival between IAD and CAD. Although quality of life outcomes were evaluated in most studies, firm conclusions cannot be made due to differences in questionnaires used and inconsistent results. Author Disclosure: S. Magnan: None. L. Pilote: None. L. Bernier: None. V. Fradet: None. E ´ . Vigneault: None. A.F. Turgeon: None. 1024 Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy W.C. Jackson, 1 S.B. Johnson, 1 C. Foster, 1 D. Li, 1 H.M. Sandler, 2 G.S. Palapattu, 1 D.A. Hamstra, 1 and F.Y. Feng 1 ; 1 University of Michigan, Ann Arbor, MI, 2 Cedars-Sinai, Los Angeles, CA Purpose/Objective(s): Concurrent/adjuvant androgen deprivation therapy (ADT) is known to improve survival for patients receiving radiation therapy (RT) as a primary treatment for localized prostate cancer. The optimal duration of ADT with RT varies by prostate cancer risk stratifi- cation. Short-term (4-6 months) concurrent ADT is considered for those with intermediate-risk disease, and long-term (2-3 years) ADT is recom- mended for those with high-risk disease. Less in known regarding the optimal duration of ADT in patients who receive either adjuvant or salvage RT (ART or SRT) for a rising prostate-specific antigen (PSA) following radical prostatectomy (RP). We sought to assess if the duration of ADT use influences clinical outcomes for patients receiving RT post-RP. Materials/Methods: Six hundred eighty patients who received ART or SRT at a single institution post-RP were retrospectively reviewed in an IRB approved analysis. We assessed the impact of ADT duration on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM) using Kaplan-Meier and Cox Proportional Hazards models. Results: One hundred forty-four patients (17%) received concurrent/ adjuvant ADT with post-RP RT. One hundred thirteen patients received SRT and 31 received ART. No difference existed between the mean duration of ADT in SRT and ART (p Z 0.6). Median follow-up post-RT was 57.4 months. Median ADT duration was 12 months (interquartile range [IQR] 6.0-23.7). Patients receiving ADT were dichotomized using median ADT duration. Patients who received <12 months of ADT were at an increased risk for BF (hazard ratio [HR]: 2.3, p Z 0.003) and DM (HR: 2.5, p Z 0.03) as compared to patients receiving >12 months of ADT. 5- year rates of DM were 6% and 23% for those receiving >12 months, and <12 months of ADT, respectively. On multivariate analysis, when controlling for pre-RT PSA, Gleason score, seminal vesicle invasion, extracapsular extension, presence of positive surgical margins, and the use of ART vs SRT, each month of ADT was associated with a 1.1-fold decrease in risk of BF (p Z 0.01), DM (p Z 0.01), PCSM (p Z 0.04), and OM (p Z 0.04). Thus, patients who received 6 months of ADT had a 1.8 fold decrease in risk of BF, DM, PCSM, and OM, whereas patients who received 24 months of ADT had a 9.8-fold decrease in risk of BF, DM, PCSM, and OM. Conclusions: For patients receiving concurrent/adjuvant ADT with post- RP RT, the duration of ADT impacts clinical outcomes. Each month of ADT was associated with a statistically significant decrease in BF, DM, PCSM, and OM. Our findings suggest that for patients receiving concur- rent/adjuvant ADT with post-RP RT, an extended course of ADT may be preferable. This is consistent with the hypothesis that patients experience BF after post-RP RT because of subclinical metastatic relapse rather than failure of RT to eradicate pelvic disease. Author Disclosure: W.C. Jackson: None. S.B. Johnson: None. C. Foster: None. D. Li: None. H.M. Sandler: None. G.S. Palapattu: None. D.A. Hamstra: None. F.Y. Feng: None. 1025 Distinguishing Grade 1 Meningioma From Higher Grade Meningiomas Without Biopsy M. Pavelic, 1 C. Specht, 2 D. Timik, 2 J. Liao, 1 S. Kanekar, 2 S. Sogge, 1 M. Glantz, 1 J. Sheehan, 3 and J. Varlotto 1 ; 1 Penn State Hershey Cancer Institute, Hershey, PA, 2 Penn State Hershey Medical Center, Hershey, PA, 3 Penn State Hershey Neuroscience Institute, Hershey, PA Purpose/Objective(s): Many meningiomas are identified radiographi- cally, assumed to be Grade I tumors, and are followed. The purpose of our investigation is to find clinical or radiographic predictors of WHO Grade II/III tumors(Gr II/III) in order to distinguish them from WHO Grade I. Materials/Methods: Patients with a pathologic diagnosis of meningioma from 2002-2009 were included if they had pre-operative MRI studies and pathology for review. Thirty of the 82 tumors were classified as Gr II/III. All pathology was reviewed and classified by WHO 2007. All Brain MRI imaging was reviewed and tumors were assessed for brain invasion, volume, maximum diameter, herniation, apparent diffusion coefficient, necrosis, vascularity (quantified by degree of enhancement, 1-4), associ- ated bleed, and cystic change. Clinical factors analyzed included symp- toms, age, sex, medications, smoking status, body mass index (BMI), Charlson comorbidity index, and diabetes. Pathology and Radiology reviews were blinded from each other and from clinical course. Univariate and Multivariate logistic regressions were used to find predictive factors for Gr II/III. Results: Univariate analysis demonstrated that the following factors were associated with Gr II/III: Brain Invasion, degree of vascularity, and volume of lesion (at p value < 0.05). Our multivariate logistic model contains predictors of tumor vascularity (p Z 0.038, Odds Ratio Z 1.83 for unit increase of vascularity), and brain invasion (p Z 0.065, Odds Ratio Z 2.48). 64% of tumor associated with grade 4 vascularity (n Z 17) had a Gr II/III compared to 27.7% of tumors with less vascularity. Brain invasion was seen in 32 patients, 50.0% of which had Gr II/III as compared to 28.3% without brain invasion. A total of 88.8% tumors with both grade 4 vascularity and brain invasion (N Z 9) were Gr II/II. Conclusions: Tumors without high-grade vascularity and brain invasion are more likely to be Grade I meningiomas. Clinical and radiographic surveillance rather than immediate surgery may be considered for these patients. Volume 87 Number 2S Supplement 2013 Digital Poster Discussion Abstracts S157

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Page 1: Distinguishing Grade 1 Meningioma From Higher Grade Meningiomas Without Biopsy

Volume 87 � Number 2S � Supplement 2013 Digital Poster Discussion Abstracts S157

looked for ongoing trials at clinicaltrials.gov and controlled-trials.com.

Referenced studies cited in published guidelines for prostate cancer as

well as in reviews and other relevant articles identified in the search were

also assessed for eligibility. The systematic review was conducted

following a pre-established protocol. RCTs comparing intermittent

(IAD) versus continuous (CAD) androgen deprivation therapy (any

regimen) for patients with prostate cancer (any stage) were considered

eligible. Primary outcomes were overall survival and quality of life.

Secondary outcomes were cancer-specific survival, progression-free

survival (biochemical and/or clinical), time to castration resistance,

skeletal-related events and side effects. Duration of off-treatment inter-

vals and testosterone levels were also considered for the IAD group. Two

reviewers performed study selection, data abstraction and risk of bias

assessment, independently. Hazard ratios using random effect models

were conducted with generalized inverse variance method. Heterogeneity

was assessed using I2 statistic.

Results: Among 8280 references, 14 studies were eligible. All studies

presented an unclear or high risk of bias for the two primary outcomes.

There was no significant difference between IAD and CAD in terms of

overall survival (HR 1.02, 95% CI: 0.93-1.13; 5 studies, 4239 patients),

cancer-specific survival (HR 1.00, 95% CI: 0.76-1.32; 3 studies, 1318

patients), and progression-free survival (HR 0.95, 95% CI: 0.78-1.14; 4

studies, 2704 patients). In 10 trials providing data on quality of life, 8 used

different version of the EORTC QLQ-C30 questionnaire and 2 used other

questionnaires. These studies observed variable results. No difference

between the two interventions was observed for hot flashes, gynecomastia,

depression, erectile dysfunction, decreased libido, and cardiovascular

death.

Conclusions: In our systematic review, we did not observe a difference in

overall survival between IAD and CAD. Although quality of life outcomes

were evaluated in most studies, firm conclusions cannot be made due to

differences in questionnaires used and inconsistent results.

Author Disclosure: S. Magnan: None. L. Pilote: None. L. Bernier: None. V.

Fradet: None. E. Vigneault: None. A.F. Turgeon: None.

1024Duration of Androgen Deprivation Therapy Influences Outcomes forPatients Receiving Radiation Therapy Following RadicalProstatectomyW.C. Jackson,1 S.B. Johnson,1 C. Foster,1 D. Li,1 H.M. Sandler,2

G.S. Palapattu,1 D.A. Hamstra,1 and F.Y. Feng1; 1University of Michigan,

Ann Arbor, MI, 2Cedars-Sinai, Los Angeles, CA

Purpose/Objective(s): Concurrent/adjuvant androgen deprivation therapy

(ADT) is known to improve survival for patients receiving radiation

therapy (RT) as a primary treatment for localized prostate cancer. The

optimal duration of ADT with RT varies by prostate cancer risk stratifi-

cation. Short-term (4-6 months) concurrent ADT is considered for those

with intermediate-risk disease, and long-term (2-3 years) ADT is recom-

mended for those with high-risk disease. Less in known regarding the

optimal duration of ADT in patients who receive either adjuvant or salvage

RT (ART or SRT) for a rising prostate-specific antigen (PSA) following

radical prostatectomy (RP). We sought to assess if the duration of ADT use

influences clinical outcomes for patients receiving RT post-RP.

Materials/Methods: Six hundred eighty patients who received ART or

SRT at a single institution post-RP were retrospectively reviewed in an IRB

approved analysis. We assessed the impact of ADT duration on

biochemical failure (BF), distant metastasis (DM), prostate cancer-specific

mortality (PCSM), and overall mortality (OM) using Kaplan-Meier and

Cox Proportional Hazards models.

Results: One hundred forty-four patients (17%) received concurrent/

adjuvant ADT with post-RP RT. One hundred thirteen patients received

SRT and 31 received ART. No difference existed between the mean

duration of ADT in SRT and ART (p Z 0.6). Median follow-up post-RT

was 57.4 months. Median ADT duration was 12 months (interquartile

range [IQR] 6.0-23.7). Patients receiving ADT were dichotomized using

median ADT duration. Patients who received <12 months of ADTwere at

an increased risk for BF (hazard ratio [HR]: 2.3, p Z 0.003) and DM (HR:

2.5, p Z 0.03) as compared to patients receiving >12 months of ADT. 5-

year rates of DM were 6% and 23% for those receiving >12 months, and

<12 months of ADT, respectively. On multivariate analysis, when

controlling for pre-RT PSA, Gleason score, seminal vesicle invasion,

extracapsular extension, presence of positive surgical margins, and the use

of ART vs SRT, each month of ADT was associated with a 1.1-fold

decrease in risk of BF (p Z 0.01), DM (p Z 0.01), PCSM (p Z 0.04), and

OM (p Z 0.04). Thus, patients who received 6 months of ADT had a 1.8

fold decrease in risk of BF, DM, PCSM, and OM, whereas patients who

received 24 months of ADT had a 9.8-fold decrease in risk of BF, DM,

PCSM, and OM.

Conclusions: For patients receiving concurrent/adjuvant ADT with post-

RP RT, the duration of ADT impacts clinical outcomes. Each month of

ADT was associated with a statistically significant decrease in BF, DM,

PCSM, and OM. Our findings suggest that for patients receiving concur-

rent/adjuvant ADT with post-RP RT, an extended course of ADT may be

preferable. This is consistent with the hypothesis that patients experience

BF after post-RP RT because of subclinical metastatic relapse rather than

failure of RT to eradicate pelvic disease.

Author Disclosure: W.C. Jackson: None. S.B. Johnson: None. C. Foster:

None. D. Li: None. H.M. Sandler: None. G.S. Palapattu: None. D.A.

Hamstra: None. F.Y. Feng: None.

1025Distinguishing Grade 1 Meningioma From Higher GradeMeningiomas Without BiopsyM. Pavelic,1 C. Specht,2 D. Timik,2 J. Liao,1 S. Kanekar,2 S. Sogge,1

M. Glantz,1 J. Sheehan,3 and J. Varlotto1; 1Penn State Hershey Cancer

Institute, Hershey, PA, 2Penn State Hershey Medical Center, Hershey, PA,3Penn State Hershey Neuroscience Institute, Hershey, PA

Purpose/Objective(s): Many meningiomas are identified radiographi-

cally, assumed to be Grade I tumors, and are followed. The purpose of our

investigation is to find clinical or radiographic predictors of WHO Grade

II/III tumors(Gr II/III) in order to distinguish them from WHO Grade I.

Materials/Methods: Patients with a pathologic diagnosis of meningioma

from 2002-2009 were included if they had pre-operative MRI studies and

pathology for review. Thirty of the 82 tumors were classified as Gr II/III.

All pathology was reviewed and classified by WHO 2007. All Brain MRI

imaging was reviewed and tumors were assessed for brain invasion,

volume, maximum diameter, herniation, apparent diffusion coefficient,

necrosis, vascularity (quantified by degree of enhancement, 1-4), associ-

ated bleed, and cystic change. Clinical factors analyzed included symp-

toms, age, sex, medications, smoking status, body mass index (BMI),

Charlson comorbidity index, and diabetes. Pathology and Radiology

reviews were blinded from each other and from clinical course. Univariate

and Multivariate logistic regressions were used to find predictive factors

for Gr II/III.

Results: Univariate analysis demonstrated that the following factors

were associated with Gr II/III: Brain Invasion, degree of vascularity, and

volume of lesion (at p value < 0.05). Our multivariate logistic model

contains predictors of tumor vascularity (p Z 0.038, Odds Ratio Z1.83 for unit increase of vascularity), and brain invasion (p Z 0.065,

Odds Ratio Z 2.48). 64% of tumor associated with grade 4 vascularity

(n Z 17) had a Gr II/III compared to 27.7% of tumors with less

vascularity. Brain invasion was seen in 32 patients, 50.0% of which had

Gr II/III as compared to 28.3% without brain invasion. A total of 88.8%

tumors with both grade 4 vascularity and brain invasion (N Z 9) were

Gr II/II.

Conclusions: Tumors without high-grade vascularity and brain invasion

are more likely to be Grade I meningiomas. Clinical and radiographic

surveillance rather than immediate surgery may be considered for these

patients.

Page 2: Distinguishing Grade 1 Meningioma From Higher Grade Meningiomas Without Biopsy

International Journal of Radiation Oncology � Biology � PhysicsS158

Author Disclosure: M. Pavelic: None. C. Specht: None. D. Timik: None. J.

Liao: None. S. Kanekar: None. S. Sogge: None. M. Glantz: None. J.

Sheehan: None. J. Varlotto: None.

1026Benefit of Adjuvant Radiation Therapy (RT) in Management ofRecurrent Atypical Meningioma (AM)S.E. Braunstein, M. Dayal, C. Tinkle, J. Chang, G. Kaur, A. Perez-

Andujar, C. Chuang, L. Ma, A. Parsa, and I.J. Barani; University of

California San Francisco, San Francisco, CA

Purpose/Objective(s): AM (WHO grade II) comprise a broad class of

brain tumors stratified between benign and anaplastic meningiomas,

characterized by heterogeneous pathologic characteristics. Several series

have demonstrated high recurrence risk of AM, with 10 yr recurrence rates

(RR) approaching 50% after gross total resection, associated with modest

overall survival. Adjuvant RT is associated with lower RR, although the

role of RT remains unclear. Given the high rates of recurrence in the setting

of varied multimodal approaches to initial AM management, we investi-

gated the role of RT in treating recurrent AM.

Materials/Methods: We performed a retrospective review of 94 patients

with AM, seen at UCSF from 1995 through 2012, for which we identified

35 patients with recurrence by imaging and treatment records. Patient and

treatment characteristics at initial diagnosis were noted, including age,

tumor location, extent of surgery, adjuvant RT, and symptomatic response.

Successive features were analyzed after recurrence along with subsequent

progression free survival (PFS).

Results: For the cohort of 35 patients who recurred, mean age at diag-

nosis was 59 yrs (range, 18 - 79 yrs). Gender distribution was 17 male

and 18 female patients. Incidence by anatomic site was: 12 convexity, 10

parasagittal, 6 sphenoid, 3 posterior fossa, 3 midline anterior fossa, and 2

other. Seventeen patients received gross total resection (GTR), and 18

had subtotal resection (STR) at initial surgery. Six patients received

adjuvant RT (2 post-GTR; 4 post-STR). Mean time to initial recurrence

was 29 mos (range, 1 mo to 96 mos). Forty percent (14 of 35) of patients

received interval resection (2 GTR; 12 STR), with evidence of

progression to WHO Grade III in 1 patient. Twenty-seven patients

received adjuvant RT: 17 with EBRT to median dose of 59.4 Gy in 33 fx;

9 with SRS to median dose of 15 Gy in 1 fx; and one implant of 3.8 mCi

I-125. For patients receiving RT, subsequent actuarial PFS was 58.5% at

2 yrs, and 29.2% at 5 yrs over a median follow-up period of 19 mos from

first recurrence. Overall survival was 74.3% at 5 yrs from initial diag-

nosis (87.5% with RT vs 37.5% without RT at recurrence, p Z 0.007).

Further analysis showed no PFS association with age, sex, location, or

RT modality at recurrence.

Conclusions:With RTOG 0539 pending, these data confirm the high RR of

AM and support adjuvant RT in their subsequent management. Short

interval to recurrence, with modest overall survival, is consistent with prior

studies. Moreover, single fraction SRS may yield local control comparable

to EBRT in select patients. Current efforts are directed towards further

resolving dose-volume relationships and RT modality for effective

management.

Author Disclosure: S.E. Braunstein: None. M. Dayal: None. C. Tinkle:

None. J. Chang: None. G. Kaur: None. A. Perez-Andujar: None. C.

Chuang: None. L. Ma: None. A. Parsa: None. I.J. Barani: None.

1027Patterns of Failure for Grade 2/3 Meningioma Treated WithReduced Margin Intensity Modulated Radiation TherapyR.H. Press,1 R.S. Prabhu,2 C.L. Appin,2 D.J. Brat,2 H.G. Shu,2

C. Hadjipanayis,2 J.J. Olson,2 N.M. Oyesiku,2 W.J. Curran,2

and I. Crocker2; 1Emory University School of Medicine, Atlanta, GA,2Emory University Winship Cancer Institute, Atlanta, GA

Purpose/Objective(s): The standard of care for grade II and III menin-

giomas is surgical resection and adjuvant radiation therapy (RT). Typical

clinical target volume (CTV) expansions for microscopic disease extension

are 1 - 2 cm. Additional planning target volume (PTV) expansions of 0.5

cm to 1 cm bring the standard total expansion to 1.5 to 3 cm. Previous

studies have generally used a variety of RT techniques with standard CTV

margins. The purpose of this study was to evaluate intracranial control and

patterns of local recurrence (LR) for grade II and III meningiomas treated

with intensity-modulated radiation therapy (IMRT) with predominantly

limited total margins of �10 mm.

Materials/Methods: The records of patients with neuropathologist diag-

nosis of grade II or III meningioma who underwent IMRT between 2003

and 2012 were reviewed. Exclusion criteria included follow-up period <4

months. Information recorded included pt and tumor characteristics,

surgical and radiation details, and tumor control. Actuarial rates were

determined by the Kaplan-Meier method from the end of RT. LR was

defined as in-field if �90% of the recurrence was within the prescription

isodose, out-of-field if �90% outside of prescription isodose, and both if

neither.

Results: Between 2002 and 2012, 59 consecutive patients underwent

IMRT for grade II/III meningioma with a median imaging follow-up

period of 26 months (range, 4 - 107 months) for alive patients. Fifty-six

patients (95%) and 3 patients (5%) had grade II and III meningiomas,

respectively. IMRT was adjuvant after surgery for 51 patients (86%) and

was definitive therapy for 8 patients (14%). The median dose for frac-

tionated IMRT was 59.4 Gy (range, 49.2 - 61.2 Gy). The median CTV,

PTV, and total margins were 5 mm, 3 mm, and 8 mm, respectively, with

unknown margins in 3 patients. Of patients with known margins (n Z 56),

81% had total margin �10 mm. LR occurred in 13 patients (22%), with 2-

year and 5-year actuarial LR of 5% and 45%, respectively. Eleven of 13

patients (85%) had a known pattern of LR. Seven patients, 2 patients, and 2

patients had in-field only, out-of-field only, and both patterns of LR. Of the

2 patients with out-of-field only LR, total margins were 25 mm and 3 mm,

respectively. Two-year and 5-year overall survival (OS) was 85% and 69%,

respectively.

Conclusions: The LR rate and OS in this series using IMRT only with total

margins (CTV + PTV) predominantly �10 mm is similar to other pub-

lished studies using standard margins. Most recurrences occur >3 years

after RT. Of the 48 patients who had margins �10 mm, only 1 failed out-

of-field only. RTOG 05-39 recommends CTV margins of 1 - 2 cm

depending on grade and extent of resection. These results support the

efficacy of treating patients with grade II and III meningiomas with

reduced margins without excess risk of out-of-field failure. Reduced

margins may be associated with lower toxicity, but further studies are

needed.

Author Disclosure: R.H. Press: None. R.S. Prabhu: None. C.L. Appin:

None. D.J. Brat: None. H.G. Shu: None. C. Hadjipanayis: None. J.J. Olson:

None. N.M. Oyesiku: None. W.J. Curran: None. I. Crocker: K. Stock;

Velocity Medical Systems. Q. Leadership; Velocity Medical Systems.

1028Mixed Proton and Photon Therapy for Benign Meningiomas: Long-term Results of a Prospective Randomized Dose Escalation StudyH.A. Shih, N.N. Niu, E. Pan, J. Daartz, B.Y. Yeap, J.E. Munzenrider,

and J.S. Loeffler; Massachusetts General Hospital, Boston, MA

Purpose/Objective(s): Optimal dose for management of benign menin-

giomas is unclear. Proton therapy permits for consideration of safer dose

escalation and was delivered at two different doses with the objective to

assess outcomes of progression free survival (PFS), overall survival (OS),

and treatment-related toxicity.

Materials/Methods: Patients with recurrent or subtotally resected benign

meningiomas were enrolled on a prospective trial of mixed proton and

photon therapy with randomization to 55.8 Gy (RBE) versus 63 Gy (RBE).

All patients received 80% of their radiation with proton therapy. Photon

radiation was delivered once weekly.