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High Grade Glioma; What Else? El-Ghoneimy E (M.D.) – Moustafa M (M.D.) Abdulla M (M.D.) Department of Clinical Oncology Kasr El-Aini School of Medicine.

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Presentation on theme: "High Grade Glioma; What Else? El-Ghoneimy E (M.D.) – Moustafa M (M.D.) Abdulla M (M.D.) Department of Clinical Oncology Kasr El-Aini School of Medicine."— Presentation transcript:

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2 High Grade Glioma; What Else? El-Ghoneimy E (M.D.) – Moustafa M (M.D.) Abdulla M (M.D.) Department of Clinical Oncology Kasr El-Aini School of Medicine Cairo University Barcelona – March, 2002

3 Neurological Deficits Already Present at Time of Diagnosis Lack of Tissue Repair Following Surgical Trauma Current Therapeutic Modalities are Lacking The Appropriate Effectiveness *2% of all malignant Diseases *Disproportionate Morbidity & Mortality * 3 rd cause of cancer related mortality

4 Why Poor Prognosis? Incompatible with life even at a relatively small burden. Symptomatic at a size between gms (3-6 X cells). Fatal when reaching about 100 gms (10 11 cells). Lack of draining lymphatics; impedes removal of necrotic debris; life- threatening ++ ICT; death of patient.

5 Survival Issues of Malignant Glioma (Huncharek & Muscat, 1998)

6 Biological Associations: P-53 mutations RB mutation mdm-2 overexpression bcl-2 mutation PDGFR,PDGF-A overexpression EGFR overexpression Mitotic Activity Invasion. Vascularization. Chemoresistance Radioresistance.

7 Complete Surgical Removal is Impossible Due to Surrounding Vital Regions. Infiltrative Nature of The Lesion. Limitations of Radiation Dose Delivery Because of Tolerance. Chemo-resistance & Lack of Drug Concentration within The Lesion

8 Dose Escalation & Altered Fractionation Schedules Conformal Radiation, Radiosurgery with the advent of Mutlileaf Collimators and IMRT. The Use of Radiation Therapy

9 Nitrosureas: Marginal Benefit. PCV Regimen: Minimal Improvement in TTP only in Anaplastic Astrocytoma not in G.M. Investigational: CPT-11, Platinum Compounds, Taxanes….etc The Use of Chemotherapeutics:

10 Basic Requirements for Investigational Therapies of Malignant Gliomas: è Non Invasive. è Least Morbidity. è No further affection of Neurological Insult. è Not associated with further deterioration of performance status.

11 Single Institution Experience

12 NEMROCK EXPERIENCE; : Ongoing Whole Brain + Boost RTh vs Localized Rth in GM & AA. Hypofractionated Rth in GM. Lomustine/Platinum X 2 + Radical Rth Vs Radical Rth in GM & AA. SRS Single Fraction vs Lomustine+VCR X3-6 in Recurrent or Residual GM & AA. The Use of TEMOZOLOMIDE in High Grade Gliomas at Relapse. Adjuvant P.O. SRT vs Conventional Rth in Low Grade Glioma

13 NEMROCK patients with high grade glioma Arm A 29 Pts CCNU/Platinum Radical Irradiation Arm B 31 Patients No Cth Radical Irradiation The Role of Neoadjuvant Cth

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16 Temozolomide at Relapse:

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20 TEMOZOLOMIDE X 6 Courses

21 Survival & Response Parameters: Median Time to Progression = 32.6 Weeks. Survival Range: Months Median Survival: 17.3 months Actuarial 12-month OAS = 63.7% Temozolomide at Relapse:

22 The Use of TEMOZOLOMIDE ADEQUATE SAFETY PROFILE NO G III-IV MORBID EVENTS + VE SUBJECTIVE EFFECT IN THE MAJORITY OF PATIENTS + VE OBJECTIVE RESPONSE

23 Future Directions Adjuvant Basis Metaststic Disease Concurrent Use with Rth Temozolomide at Relapse:

24 Rational For High Precision External Beam RT: Dose Reduction To Normal Tissue Dose Escalation To CTV

25 Biological Considerations: Significant Improvement in Tumor Coverage + Significant Reduction to Normal Tissue Dose Dose Escalation to CTV Maximum Locoregional Tumor Control ? Improved Survival

26 Radiosurgery at Relapse:

27 Headring and Mask System Headring and Mask System Localizer box Localizer box Couchmount Couchmount QA Hardware QA Hardware Target Positioner box Target Positioner box Conical Collimator Set Conical Collimator Set Conformal blocks Conformal blocks Headring and Mask System Headring and Mask System Localizer box Localizer box Couchmount Couchmount QA Hardware QA Hardware Target Positioner box Target Positioner box Conical Collimator Set Conical Collimator Set Conformal blocks Conformal blocks NEMROCK BrainSCAN Hardware consists of:

28 Head ring For flexible patient fixation and referencing For single fraction & consists of: For flexible patient fixation and referencing For single fraction & consists of: Carbon fiber post - variable angle and position - maximum vertical length for Deep seated lesions. Carbon fiber post - variable angle and position - maximum vertical length for Deep seated lesions. Robust and lightweight frame ( Positioned at least 2 cm below lesion) Robust and lightweight frame ( Positioned at least 2 cm below lesion) Two torque wrenches for pressure adjustment of pins Artifact-free fixation pins for CAT scan with ceramic tips (S.C local anesthesia is applied at fixation site) Artifact-free fixation pins for CAT scan with ceramic tips (S.C local anesthesia is applied at fixation site)

29 CT Localization Treatment Planning Steps Automatic Image Fusion (if required) Outlining of lesion and critical organs Treatment planning Dose Verification - Isodose Lines and Dose-Wash - DVH - 3D Dose representations

30 First radiological assessment among 40 patients with residual or recurrent brain tumorsFirst radiological assessment among 40 patients with residual or recurrent brain tumors (Most of the patient in both groups experienced PR followed by SD and CR)(Most of the patient in both groups experienced PR followed by SD and CR) (NEMROCK, April 1999-April 2001)(NEMROCK, April 1999-April 2001) (P-value: 0.603)(P-value: 0.603)

31 First clinical and neurological assessment among 40 patients with residual or recurrent brain tumorsFirst clinical and neurological assessment among 40 patients with residual or recurrent brain tumors (Most of the patient in both groups experienced improvement followed by persistence)(Most of the patient in both groups experienced improvement followed by persistence) (NEMROCK, April 1999-April 2001)(NEMROCK, April 1999-April 2001) (P-value: 0.41)(P-value: 0.41)

32 PFS dating end of Chemotherapy & date of SRS showed insignificant survival benefit in the Chemotherapy arm (P- value: 0.1)

33 Overall survival dating initial diagnosis showed insignificant survival benefit in favor of the SRS arm. (P- value: 0.19)

34 Immediate Post-SRS & SRT Side Effects

35 Establishment of SRS & SRT. > 300 Cases Cranial & Extra- Cranial Targets are Treated. Ongoing Research. Committee Decision Upgrading. Current Situation:

36 Why to Irradiate More if we can Irradiate Less?


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