Alessandra Gorgulho, MD, MSc

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Manejo do Meningioma que compromete o seio cavernoso: quando eu irradio Alessandra Gorgulho, MD, MSc Chefe Clínico-Científica Centro HCor de Neurociências Professora Visitante, Departamento de Neurocirurgia, UCLA Presidente Sociedade Brasileira de Radiocirurgia V Congresso Internacional de Neuro- Oncologia - 28-29 de Abril 2017, São Paulo

Meningiomas Most frequent primary CNS tumor (34%) Simpson Grade Grade I Complete with attached dura 9% Grade II Complete with 19% dural coagulation Grade III Partial resection Grade IV Biopsy 29% 40% Recurrence Rate of III and IV is high: 50-90%

SRS Simpson I

SKULL BASE Meningioma Location difficulty to achieve Simpson Grade I in skull base lesions. Simpson grade of resection is more important than location of the lesion. Keep in mind that SRS results DO NOT depend on the level of resectability of a skull base meningioma! Radiosurgery is a BETTER option for non-resectable small to medium size SKULL BASE meningiomas (i.e., WITHOUT mass effect)!

Sphenoid Wing Meningioma Treatment? Microsurgery or Radiosurgery

Sphenoid Wing Meningioma with Cavernous Sinus Invasion Treatment? Radiosurgery

Mass Effect! Treatment? Decompressive Microsurgery SRS or SRT to the residual

This is NOT Decompressive Microneurosurgery!

Cavernous Sinus Lesions When Histological confirmation is necessary? Mandatory to have histological diagnosis: Atypical presentation: pain, fever, rapid progression, malignancy elsewhere Atypical radiological findings: rapid progression, edema and necrosis Surgical Options: Foramen Ovale Needle Biopsy Endoscopic or Open Surgery Diagnosis obtained: 86% cases Sensitivity = 0.83 Specificity = 1

UCLA Grading System for Para-sellar and other locations Meningiomas* Grade I: Restricted to the cavernous sinus/parasellar region (<3cm) Grade II: Expansion to the clivus/petrous region Grade III: Compression of the optic structures (>3cm) Grade IV: Compression of the Brainstem Grade V: Bilateral involvement of the cavernous sinus Grade VI: Optic Sheath *Modified from De Salles et al 2001 Grade I: Tumors smaller than 3 cm in largest diameter (14 cc) in any locations Grade III: Tumors larger than 3 cm in largest diameter (14 cc) in any locations

Cavernous Sinus Meningiomas Eligibility to Single Fraction Grade I: safety to - Optic Apparatus - Cranial Nerves (within cavernous sinus) - Brainstem Torres, Frighetto, De Salles et al - NS Focus 2003

Axial Sagittal Coronal Grade II 3D SRS 13 Gy 1.3 cc > 9.0Gy

Dose Constrains to II, III, IV, V and VI NN OA: 8 Gy III, IV,V & VI: Up to 40 Gy

Dose Constrains to Optic Apparatus GK, retrospective, 222 pts, cv meningioma (143), pit adenoma (72), craniopharyngioma (7) mean clinical fup: 83 mo (7y), mean radiological fup: 123 mo (10y) Visual Preservation using Single Dose (SRS) Maximum Radiation Dose OA RION 8 Gy 0% >8 to 10 Gy 0% >10 to 12 Gy 0% 12 Gy 10% Maximum Dose Point of 10 Gy : RION of < 1% Leavitt et al IJROBP 2013

SRT Treatment 3 years post-srt 4 years post-srt GRADE III = SRT 58y, female, blind on the left Tumor involving the chiasm SRT to preserve vision on the right ON & Chiasm 50.4 Gy, 28fx, 1.8 Gy/fx

IMRT PLAN: 50.4 Gy, 28 Fx GRADE III Involvement OA 7 IMRT Beams PTV=90.11cm 3 GTV=65.79cm 3 SRT

Axial Sagittal Coronal 12cc > 40Gy 3D 4cc > 50Gy 47 y, female, Optic and Brainstem compression 50.40 Gy, 29 cc, IMRT plan, 2 mm margin PLAN: COVERS THE TAIL GRADE IV SRT

Visual Preservation in Stereotactic Radiation Tolerance of the Optic Apparatus Total Dose Incidence of Optic Neuropathy Dose per fraction 1.8 Gy > 1.8 Gy < 59 Gy 0/87 (0%) 0/8 (0%) 59 Gy 5/61 (8%) 10/25 (40%) Parsons IJROBP 30:755-763, 1994; Mayo et al IJROBP 2010

SRT as primary treatment modality Incomplete resection: difficulty to define the target - postoperative changes vs. residual tumor Mistarget: local tumor control Overcome with fractions (larger margins) GRADE V SRT 46.8 Gy, 1.8 Gy/26 fx 5 dynarcs, 2mm margin 28.40 cc

Optic Nerve Meningioma GRADE VI SRT 50.40 Gy 28 Fx of 1.8 Gy Preservation and Improvement of Vision

115 cases, 40% had previous surgery Median dose: 16Gy, median fup: 89 mo LTC: 99% at 5 years and 93% at 10 years Cranial Nerve Deficits Improvement: 42/136 (31%) Primary SRS : improvement = 41% With Prior Surgery = 20% (p <0.01) Permanent Complications: 14/114 (12%) TN dysfunction: 9 Diplopia: 2 Ischemic Stroke: 2 Hypopituitarism: 1 Multivariate Analysis: predictor of complications - larger tumor volume 9.3 cc = 3% vs. > 9.3 cc = 21% JNS 119:675, 2013

LTC: 99% at 5 years 93% at 10 years 2-year, 5-year, and 10-year rates of complications were 7%, 10%, and 15% Cranial Nerve Improvement: 42/136 (31%)

LINAC SRS Spiegelman et al J NeuroOncol 2010 102 Cavernous Sinus Meningiomas, Mean Fup: 68 months (12 180 mo) Actuarial 5-year control rate = 98% Radiological Outcome: 59pts (58%) reduction of 20 95% 41 pts (40%) stable tumor Tumor Volume Reduction: < 5y f-up: 43% Onset time prior to SRS: 2 (2%) tumors grew (36 & 84mo after SRS) >5y f-up: 65% (p=0.05 chi square test) <1 year prior to SRS = 43 cranial neuropathies Resolution/ Improvement: 21 (49%) Overall Improvement or Resolution = 32% > 1 year prior to SRS = 58 cranial neuropathies Improvement = 11 (19%) (p= 0.03 chi square test)

5300 Meningiomas

254 pts North American Gamma Knife Consortium 140 pts: upfront SRS 114 pts: w/ prior surgery Mean follow-up: 71.1 mo (range: 6 252 months) PFS at 3, 5, 8, 10, 12 ys = 97, 93, 87, 84, 80 % respectively Clinical Response: 93.6 % of patients = no change or improvement 6.4 % = progression of neurological symptoms Radiological Response: Tumor Volume Increased = 9 % Stable = 52 % Decreased = 39 % Complications: 7 shunts (1 tu progression), 7 resections, 1 SRT (all tu progression)

Oct 1992 At 75 y Jun 2004 At 87 y Several previous operations for a large petroclival meningioma First resection: 25 years before, at age 50 SRS 12 Gy Conventional radiation therapy Neurological examination: R side facial numbness hearing loss MRI Fup: tumor growth 87 years old 12 Years Fup Karnofsky 90 Dizziness

45 pts, 44 with cranial neuropathies Compression OA: 30 pts Mean Vol: 14.4cc (3.8cm) Median Dose: 50.4 Gy Median fup: 36 mo LTC: 97.4% at 3 years Tumor Growth: 1 (2%) at 18 mo post SRT Tumor shrinkage: 18% CRANIAL NERVES FUNCTION: Diplopia: 4/9 Visual deficit: 3/14 Facial numbness: 1/9 Headache: 1/6 No New Deficits Cranial NN Improvement: 20% (80% stable) During SRT: 4 HA, 3 fatigue, 1 retroorbital pain 12 mo post SRT 51 y, female 48.6 Gy, 24.62 cc

2001: SRT 50.4 Gy, 28 fr, 17.86 cc 2005: 4y post SRT 42y, female 1996: HA & vision MRI: multiple meningiomas 2000: resection of a cavernous sinus meningioma. Postop: R eye blindness, recovered a little bit overtime GRADE V: Bilateral CS & Chiasm

SRS SRS & SRT Series SRT

A.1) Date of SRS B.1) 3 Mo Post SRS A.2) 3 Mo Post -SRS A.3) 5 Mo Post -SRS A.4) 7 Mo Post -SRS B.2) 5 Mo Post -SRS B.3) 7 Mo Post -SRS B.4) 29 Mo Post -SRS 66 y female, 2 cm sphenoid wing meningioma in relation to the sphenoid venous drainage Treatment: SRS with 16 Gy, 4.2 cc, 4 dyn arcs Seizure and mental confusion - Management: steroids (2mo) & anticonvulsivants

Carotid Artery Obliteration 66-y, female, diplopia, 10 iso, 16.8 cc lesion, 16Gy (max= 32 Gy) 39 mo later: Stroke -hemiparesis and expressive aphasia Roche et al: 1 patient w/ temporary central facial palsy 14 mo after SRS & shown to have occlusion of her intracavernous internal carotid artery. Dose to the artery: 36Gy Caution: attempt to minimize the radiation dose to major arteries whenever possible Pollock et al IJROBP 2005

SRS Date 5 years post-srs Dura Tail FAILURE! Grade IV - 45y female, status postop + post SRS with 12 Gy Tail no standard guidelines: Encompass some of the tail into the target volume

Literature Review - Surgery/SRS/SRT

Summary SRS/SRT Results for CV Meningiomas Established treatment modality: - Adjuvant to partial resection - Primary tt for lesions not amenable to complete resection - LOCAL TUMOR CONTROL (LTC) SRS = 97% LTC in 5 y & 93% LTC in 10 y SRT = 97.5% LTC in 5 years and 90% LTC in 10 y Improvement of Previous Cranial Deficits: 20-42% Complications: Cranial nerve deficits Post radiation peri-tumoral edema Motor deficit/vascular occlusion Hydrocephalus

Small & Asymptomatic: Follow up MRI Convexity: Resection: goal = GTR SRS/SRT: adjuvant if needed advanced age, bad clinical status Skull Base: Small & Symptomatic or Growing: SRS Large: Surgery: DECOMPRESSION SRT Combination

HCor Neurosurgery, Radiation Oncology & Medical Physics: Antonio De Salles, MD, PhD Alessandra Gorgulho, MD, MSc Bruno Fernandes, MD João Vitor Salvajoli, MD, PhD Bernardo Salvajoli, MD Crystian Saraiva, PhD Anderson Pássaro, MD Paula Toledo, NP Research Team: Camila Lasagno, Coordinator Lucas Petri Damiani, PhD 7 Congresso SBRC 3 Congresso Íbero- Americano RC Nov 2018 ISR S