• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Brain Tumors
 

Brain Tumors

on

  • 390 views

Comprehensive overview of brain Cancers: diagnosis, and treatment

Comprehensive overview of brain Cancers: diagnosis, and treatment

Statistics

Views

Total Views
390
Views on SlideShare
390
Embed Views
0

Actions

Likes
0
Downloads
38
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Brain Tumors Brain Tumors Presentation Transcript

    • Ahmed Zeeneldin
    • žA patient 40 years oldž Headache of one month durationž Seen by many doctors and received different treatments with no improvement but rather worseningž CT revealed a brain mass 3x3 cmž What is your approach? Ahmed Zeeneldin 10/09 2
    • ž We suspect brain tumor?ž Could it be something elsež What it could be?ž How to differentiate?ž How to reach a definitive diagnosis?ž What is the prognosis?ž What are the treatment options?ž What are the expected results? Ahmed Zeeneldin 10/09 3
    • ž Could it be something else? Ahmed Zeeneldin 10/09 4
    • ž Could it be something else? ¡ Abscess ¡ Congenital remnants ¡ Hemorrhage ¡ Thrombosis Ahmed Zeeneldin 10/09 5
    • ž Is it common to see BT Ahmed Zeeneldin 10/09 6
    • ž Is it common to see BTž USA in 2008: ¡ 21,810 new cases ¡ 13,070 deaths.ž Egypt in 2003: ¡ Mortality? ¡ New cases: Gharbia NCI Ahmed Zeeneldin 10/09 7
    • Ahmed Zeeneldin 10/09 8
    • ž Primaryž Secondaryž What is the commonest? Ahmed Zeeneldin 10/09 9
    • ž Primaryž Secondary: commonest ¡ 10 times that of PBT ¡ 20-40% of patients with systemic will develop brain metastases. ¡ lung, breast, an unknown primary, and melanoma Ahmed Zeeneldin 10/09 10
    • Ahmed Zeeneldin 10/09 11
    • ž Do age and sex matter? Ahmed Zeeneldin 10/09 12
    • ž Do age and sex matter?ž Age: ¡ Young: 1ry ¡ Old: 2ryž Sex: ¡ Male: lung, pancreas ¡ Female: breast, thyroid Ahmed Zeeneldin 10/09 13
    • ž Does the clinical picture of the SOL differ? Ahmed Zeeneldin 10/09 14
    • ž Does the clinical picture of the SOL differ?ž Triad: ¡ Headache ¡ Vomiting ¡ Blurring of vision /papilledemaž Site specific symptoms/signs: ¡ Frontal: thinking and emotions ¡ Parietal: sensory /motor ¡ Temporal: hearing ¡ Occipital: vision ¡ Cerebellum: equilibrium and coordination ¡ Deep centers ¡ Cranial nerve compression ¡ Two sides Ahmed Zeeneldin 10/09 15
    • ž Doesthe clinical picture of the SOL differ?ž MULTIPLICITY ¡ Imaging ¡ Clinical: ¢ Bilateral focal presentation ¢ Unilateral multiple focal symptoms Ahmed Zeeneldin 10/09 16
    • ž Source:ž Whatare the diseases that commonly metastasize to brain? Ahmed Zeeneldin 10/09 17
    • ž Source:ž Whatare the diseases that commonly metastasize to brain? Ahmed Zeeneldin 10/09 18
    • ž Source:ž How to identify the source? Ahmed Zeeneldin 10/09 19
    • ž Source:ž How to identify the source? ¡ Clinical: Hx, Exam and Investigations ¢ Hx: — Breast mass — Cough — Pains — Symptoms : GI, Urinary ¢ Exam : Ahmed Zeeneldin 10/09 20
    • ž Source:ž How to identify the source? ¡ Clinical: Hx, Exam and Investigations ¢ Investigations: — Labs: ¤ Routine: CBC, LFT, KFT, urine ¤ Others: tumor markers ¤ BM — Imaging: ¤ CXR ¤ US ¤ CT ¤ MRI ¤ others Ahmed Zeeneldin 10/09 21
    • ž How to reach a diagnosis? Ahmed Zeeneldin 10/09 22
    • ž How will you do?ž Pathological diagnosisž Staging (IV)ž Prognosisž Treatment: ¡ Primary: colon, leukemia, lymphoma ¡ Other mets: Liver or lung ¡ CNS Mets: ¢ Local: surgery (if solitary, resectable.. lung), RT (multiple) ¢ Systemic therapy: BBB Ahmed Zeeneldin 10/09 23
    • ž What will you do? Ahmed Zeeneldin 10/09 24
    • ž What will you do?ž Biopsy ¡ Open: surgical ¡ Closed: imaging guided ¡ Not feasible Ahmed Zeeneldin 10/09 25
    • ž Yougot the pathology reportž What are the histological types of PBT? Ahmed Zeeneldin 10/09 26
    • ž Yougot the pathology reportž What are the histological types of PBT? Ahmed Zeeneldin 10/09 27
    • Ahmed Zeeneldin 10/09 28
    • ž No staging system.ž Can CNS tumors metastasize? Ahmed Zeeneldin 10/09 29
    • ž Whatare the essentials that should be at hand before you think of treatment? Ahmed Zeeneldin 10/09 30
    • ž What are the essentials that should be at hand before you think of treatment?ž Respectable pathology reportž Reliable imaging Ahmed Zeeneldin 10/09 31
    • ž Whatfactors you will consider when planning treatment? Ahmed Zeeneldin 10/09 32
    • ž What factors you will consider when planning treatment?ž Tumor sitež Tumor numbersž Tumor sizež Tumor typež The patientž The available therapies and expertise Ahmed Zeeneldin 10/09 33
    • ž What factors you will consider when planning treatment?ž Tumor site ¡ Deep seated tumors and near vital structures vs inert areas Ahmed Zeeneldin 10/09 34
    • ž What factors you will consider when planning treatment?ž Tumor numbers: ¡ Single: surgery ¡ Multiple: RT Ahmed Zeeneldin 10/09 35
    • ž What factors you will consider when planning treatment?ž Tumor size ¡ Small ¡ large Ahmed Zeeneldin 10/09 36
    • ž What factors you will consider when planning treatment?ž Tumor type ¡ Low grade vs high grade Ahmed Zeeneldin 10/09 37
    • ž Include: ¡ Grade III astrocytomas (anaplastic astrocytoma) ¡ Grade IV astrocytomas (glioblastoma multiforme)ž Incidence: ¡ most common PBT in adults ¡ Age : 45-55 yearsž Behaviour ¡ diffusely infiltrate surrounding tissues ¡ frequently cross the midline Ahmed Zeeneldin 10/09 38
    • ž Clinical picture ¡ ICP: HVB ¡ Seizures: direct, indirect ¡ Focal neurological signs: ¢ Tumor size and site ¢ Edema (can be extensive) ¢ Usually NO he or calcification Ahmed Zeeneldin 10/09 39
    • ž Prognostic factors: ¡ histologic diagnosis, ¡ age, ¡ PS, ¡ type and duration of symptoms, and ¡ extent of surgical resection(Curran et al. J Natl Cancer Inst 1993;85:704-710.) Ahmed Zeeneldin 10/09 40
    • ž What factors you will consider when planning treatment?ž The patient ¡ Fit ¡ Unfitž Availability: ¡ neurosurgeon, ¡ RT techniques, ¡ Systemic therapy Ahmed Zeeneldin 10/09 41
    • ž Essential role ¡ Complete excision ¡ Minimum morbidity ¡ Accurate diagnosis Ahmed Zeeneldin 10/09 42
    • ž Decision of surgery (1) age and performance status (2) proximity to “eloquent” areas of the brain; (3) feasibility of decreasing the mass effect with aggressive surgery; (4) resectability of the tumor (number and location of lesions); and (5) For recurrent disease, the time since the last surgery Ahmed Zeeneldin 10/09 43
    • ž Aims in HGA ¡ diagnosis, ¡ alleviate symptoms of ^ ICT or compression, ¡ decrease the need for corticosteroids, and ¡ increase survivalž Extensive Surgery vs. Biopsy ¡ ^ OS esp in >50 & PS 1 ¡ Both in do-no-vo and recurrent cases Ahmed Zeeneldin 10/09 44
    • ž Type of surgery ¡ stereotactic biopsy, ¡ open biopsy or ¡ debulking procedure, ¡ subtotal resection, or ¡ gross total tumor resection ¡ microneurosurgical techniques Ahmed Zeeneldin 10/09 45
    • ž Results of Surgery alone in HGA Ahmed Zeeneldin 10/09 46
    • ž Results of Surgery alone in HGA ¡ MOS: 4 months Ahmed Zeeneldin 10/09 47
    • ž Type of surgery Stereotactic biopsy: ¡ Head ring ¡ Imaging ¡ Localization ¡ Skull hole ¡ Guided needle biopsy Ahmed Zeeneldin 10/09 48
    • ž Technique: ¡ Brachytherapy (BT), ¡ External beam (EB): ¢ Fractionated EBRT is the most common approach. ¢ stereotactic radiosurgery (Gamma Knife). ¢ stereotactic fractionated RT,ž Field: ¡ Gross tumor volume and 1-2 cm margins. Ahmed Zeeneldin 10/09 49
    • ž Technique: ¡ Fractionated EB RT is standard ¡ Brachytherapy (needles) & radiosurgery are of no added benefitsž Results: ¡ Increases OS of BSC and BCNU alone ¡ RCT, HGG, post surgery ¡ 1. Walker et al J Neurosurg. 1978 Sep;49(3):333-43. ¡ 2. Roa et al, J Clin Oncol 2004;22:1583-1588 Surgery+ BSC BCNU (carmustine) RT CRT ref 80 mg/SM D1-3 q 42-48 D 50-60 Gy MS (W) 14 18 35 35 1 1-y OS (%) 3 12 24 2 Ahmed Zeeneldin 10/09 50
    • ž Radio-chemotherapy ¡ Nitrosureas (BCNU vs MeCCNU) ¡ No much benefit in ~500 ptsž 1. Walker et al, N Engl J Med. 1980 Dec 4;303(23):1323-9 Surgery+ Semustine RT RT+ RT+ re (MeCCNU) Carmustine Semustine f (BCNU ) 1.5-Y OS Better (NS) 1 Ahmed Zeeneldin 10/09 51
    • ž Radio-chemotherapy ¡ PCV combination (procarbazine, lomustine [CCNU], and vincristine) ¡ procarbazine 100 mg/m2 days 1 to 10, lomustine 100 mg/m2 day 1, and vincristine 1.5 mg/m2 (max 2 mg) day 1 ¡ No benefit in > 600 Ptsž 1. MRC, J Clin Oncol. 2001 Jan 15;19(2):509-18.Surgery+ RT RT+ (PCV q 6 w x 12) refMS (Months) 9.5 10 1 Ahmed Zeeneldin 10/09 52
    • ž Radio-chemotherapy ¡ Meta-analysis (1993)of > 3000 pts ¡ CT is mainly nitrosureas ¡ Modest benefit in OSž 1. Fine et al, Cancer. 1993 Apr 15;71(8):2585-97 Surgery+ RT CRT ref Absolute gain in MS (%) at 1-Y +10% 1 Absolute gain in MS (%) at 2-Y +8% Ahmed Zeeneldin 10/09 53
    • ž Radio-chemotherapy ¡ Meta-analysis (2002) of > 3000 pts ¡ Small but defnitive benefit in OSž 1. GMT, Cochrane Database Syst Rev. 2002;(4):CD003913. Surgery+ RT CRT ref MS (%) at 1-Y 40% 46% 1 Absolute gain in MS (Months) at 1-Y +2m Ahmed Zeeneldin 10/09 54
    • ž Stereotactic radiosurgery (Gamma Knife):ž ONE TIME ONLY ¡ Head ring ¡ Imaging ¡ Planning ¡ Fixation to machine ¡ Radiation Ahmed Zeeneldin 10/09 55
    • ž Alkylating agentž Indicated in ¡ Newly diagnosed & Recurrent GM ¡ Recurrent anaplastic astrocytomaž Oral capsules Ahmed Zeeneldin 10/09 56
    • ž Key study byStupp et al, N Engl J Med. 2005 Mar 10;352(10):987-96.ž RCTž ~600 pts, new GBM ¡ RT: 60 Gy (2x30/6W 5D/W) ¡ CRT: RT+ Temo ¢ During RT: 75 mg/SM during RT (7D/W) ¢ After RT (D1-5 q 4 W for6 months): — 1st : 150 mg/SM — 2nd-6th : 200 mg/SM Ahmed Zeeneldin 10/09 57
    • ž Key study by Stupp et al, N Engl J Med. 2005 Mar 10;352(10):987-96.ž Results RT RT+TemoMS (months) 12 14.62-Y OS 10% 26%G3-4 Hemato toxicity 7% Ahmed Zeeneldin 10/09 58
    • Stupp et al, N Engl J Med. 2005 Mar 10;352(10):987-96.Ahmed Zeeneldin 10/09 59
    • ž Key study byStupp et al, N Engl J Med. 2005 Mar 10;352(10):987-96.ž Comments: ¡ What caused the benefit? ¢ The concomitant OR ¢ The adjuvant OR ¢ Both ¡ O-6-methylguanine-DNA methyltransferase (MGMT): ¢ DNA repair enzyme confers resistance to alkylating agents ¡ chromosomal loss of 1p or combined 1p19q loss: confers sensitivity to alkylator chemotherapy ¡ PCP prophylaxis Ahmed Zeeneldin 10/09 60
    • ž RCT study byž Levin et al, Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4.ž Arms ¡ RT+ CCNU: 257 pt ¡ RT+ PCV : 175ž Results RT+CCNU RT+PCVGBM TTP Longer (NS) OSAnaplastic Astrocytoma TTP Longer (S) OS Almost doubled Retrospcetive analysis later on showed that there is no survival benefit for PCV Pardos et al, J Clin Oncol. 1999 Nov;17(11):3389-95. Ahmed Zeeneldin 10/09 61
    • ž Radio-chemotherapy ¡ PCV combination (procarbazine, lomustine [CCNU], and vincristine) ¡ procarbazine 100 mg/m2 days 1 to 10, lomustine 100 mg/m2 day 1, and vincristine 1.5 mg/m2 (max 2 mg) day 1 ¡ No benefit in > 600 Pts ž MRC, J Clin Oncol. 2001 Jan 15;19(2):509-18. RT RT+ (PCV q 6 w x 12)MS (Months) 9.5 10 Ahmed Zeeneldin 10/09 62
    • ž Temozolamide: 1st line GBMž Nitroseurreas: may be in AAž Second line ¡ PCV ¡ Procarbazine ¡ Irinotecan ¡ Ciaplatin and carboplatin in single or combinations ¡ Temp+cisplatin ¡ Avastin (Beva)+ irinotecan Ahmed Zeeneldin 10/09 63
    • ž Biodegradable Polymer impregnated With BCNUž Placed intraoperativež In surgical cavityž After Frozen pathology suggestive of HGGž Up to 8 pieces can be usedž Active for 3 weeksž It is a form of topical or interstitial chemotherapyž Remnants can be seen on MRI Ahmed Zeeneldin 10/09 64
    • ž Indications: ¡ High-grade glioma ¡ New or recurrent ¡ After surgery ¡ Before EBRTž Benefits: ¡ Increased OS ¡ Decreased recurrences ¡ Can replace or complement systemic chemotherapy Ahmed Zeeneldin 10/09 65
    • ž Key study by Westphal et al Neuro Oncol. 2003 Apr;5(2):79-88.ž RCT, 240 pts with de no vo GBM ¡ After surgery ¢ BCNU wafer ¢ Placebo Wafer ¡ Then EB RT Placebo wafer BCNU waferMS (Months) P=0.03 11.6 13.9CSF leak 1% 5%Intracranial 2% 9%hypertension Ahmed Zeeneldin 10/09 66
    • ž Decision based on:ž Age, PS, Histology, response to initial Tx, Time to recurrence, pattern of recurrence. ¡ Local tumor: re-surgery +/- re-wafer +/- re-RT ¡ Surgery not feasible: chemotherapy (Temo, PCV, others) +/- RT ¡ BSC Ahmed Zeeneldin 10/09 67
    • ž Include ¡ fibrillary, ¡ protoplasmic, ¡ gemistocytic types ¡ other rare ¢ pleomorphic xanthoastrocytoma, ¢ subependymal giant cell astrocytoma, and ¢ subependymoma. Ahmed Zeeneldin 10/09 68
    • ž Clinically ¡ Seizures ¡ headache, ¡ weakness.ž Age: younger than HGA, 37 years.ž Survival: ¡ Children: 80% at 10 y ¡ Over 40y: MS of 5 Yž Possible Transformation to HGA in 5-10 Y Ahmed Zeeneldin 10/09 69
    • ž Imaging (CT, MRI):ž nonenhancing, low- attenuation lesions. Low grade tumors with enhancement: ganglioglioma (left) and pilocytic astrocytoma (right) Oligodendroglioma with calcification GBM T2MRI, enhancement Ahmed Zeeneldin 10/09 70
    • ž Treatmentž Maximum possible surgery: ¡ Exclude areas of HGA ¡ Prevents transformation to HGA ¡ Enhance RT effectsž Then EBRT Immediate Delayed RT RT OS at 5y 63% 66% MOS 7.4 y 7.2 y DFS at 5y 44% 37% P=0.02 Seizures Less more Suits Young Older (>45 y) Ahmed Zeeneldin 10/09 71
    • ž Rarež Survival: ¡ LG: ~10 y ¡ HG: 3-5 yž Treatment: ¡ Maximum possible surgery ¡ EBRT ¢ Immediate : HG and LG in older (>45 y) pts ¢ Delayed: LG young and completely resected ¡ Chemotherapy (temo or PCV): ¢ loss of 1p or 1p19q confers sensitivity ¢ May be given wit RT or at recurrence Ahmed Zeeneldin 10/09 72
    • ž Affectsadults and childrenž Treatment: ¡ Maximum possible surgery ¡ EBRT ¢ LG: limited field ¢ HG : larger field ¡ Chemotherapy : no defined role and may be used on recurrence (VP16, Temo, NU, Platinum) Ahmed Zeeneldin 10/09 73
    • ž Primaryž Secondary: commonest ¡ 10 times that of PBT ¡ 20-40% of patients with systemic will develop brain metastases. ¡ lung, breast, an unknown primary, and melanoma Ahmed Zeeneldin 10/09 75
    • ž Hematogenous spreadž Site: ¡ junction of grey and white matter (Narrow vessels) ¡ Cerebral (80%), cerebellar (15%), brain stem (5%) ¡ Multiple lesions (70%)ž Evident primary in 80%ž Associated lung mets in 60% Ahmed Zeeneldin 10/09 76
    • ž Diagnosisž Clinically ¡ As primary BT ¡ + Primaryž Brain Imaging: ¡ MRI ¡ CTž Primary detection: ¡ chest x-ray or CT, ¡ abdominal & pelvic CT, or ¡ FDG-PET : 2-3 lesions, and no detectable primary ¡ If no other readily accessible tumor is available for biopsy, a stereotactic or open biopsy resection is indicated to establish a diagnosis Ahmed Zeeneldin 10/09 77
    • ž Treatment decision:ž Extent: ¡ Limited : 1-3 ¡ Multiple: >3 lesionsž Primary disease status and treatment options: Ahmed Zeeneldin 10/09 78
    • A. Treatment of limited metastasesž 1. Controllable primary ¡ Brain mets resectable: ¢ Surgery (for largeT) then WBRT ¢ Sterotactic radiosurgery then WBRT( for small single met) ¢ Sterotactic radiosurgery alone ¡ Brain mets irresectable: ¢ WBRT and/or radiosurgery can be used Ahmed Zeeneldin 10/09 79
    • A. Treatment of limited metastasesž 2. uncontrollable primary: ¡ Rapidlly Progressive primary ¡ Expected poor OS (<3 months) ¡ WBRT alone Ahmed Zeeneldin 10/09 80
    • Ahmed Zeeneldin 10/09 81
    • B. Treatment of multiple (>3)metastases¡ WBRT¡ Rarely surgery:¡ Life threatening mass effect, hge,hydrocephalus Ahmed Zeeneldin 10/09 82
    • Neoplastic Meningitis (NM):ž Definition: multifocal seeding of the leptomeninges by malignant cells: ¡ From solid tumor: carcinomatous NM ¡ From lymphoma: lymphomatous NMž Rare but serious (OS in weeks if untreated)ž Route of access to CSF: ¡ Hematogenous ¡ Direct spreadž Primaries: Breast, lung cancer, and melanoma.ž CSF cycle: ventricles, foramen of Magendie & Luschka, spinal canal, cortical convexities, arachnoid granulations Ahmed Zeeneldin 10/09 83
    • Neoplastic Meningitis (NM):ž Treatment: ¡ Fractionated EBRT ¡ Intrathecal chemotherapy ¢ Liposomal Ara-c, high dose Mtx, thiotepa ¡ Primary cancer treatment: e.g. breast Ahmed Zeeneldin 10/09 84
    • ž PBT are commoner than SBTž Presents by ^ ICT, focal signsž Suggested by imaging CT, MRIž Biopsy is essentialž Many factors decide the plan of managementž Maximum surgical resection is advisablež RT is crucialž BCNU wafers in surgical cavityž Temozolamide during RT and adjuvant for 6 months for HGGž PCV can be used for AA or recurrent diseasesž Second linesž In SBT: see if primary is controllable or notž In SBT: see if brain lesions are limited or not Ahmed Zeeneldin 10/09 85