Institute of Oncology & Radiobiology. Havana, Cuba. INOR 1
Transition from 2-D 2 D to 3-D 3 D conformal radiotherapy in high grade gliomas: : our experience in Cuba Chon. I, MD - Chi. D, MD - Alert.J, MD- Alfonso. R, PhD.- Ropero. R, MD. Department of Radiotherapy Institute of Oncology & Radiobiology. Havana, Cuba.
The aims of 3D-CRT are to achieve conformity of the high dose region to the target volume and consequently to reduce the dose reaching the surrounding normal tissues. This should reduce both acute and late morbidity. If the adverse effects of treatment can be reduced in this way, the dose of the target volume can be increased with the expectation of improving survival. It is now the standard practice in developed countries, treating many types of tumours with curative intent. 3
THE GOALS OF THE PRESENT STUDY ARE: Firstly, to compare the effects of radiation dose- escalation in adult patients, treated with third dimension conformal radiation therapy (3-D D CRT) with those patients who had just the second dimension radiation therapy (2-D D RT). All patients have high grade gliomas. Secondly, to show the benefits of third dimension conformal radiation therapy (3-D D CRT) as the treatment of choice for malignant gliomas in the postoperative stage. 4
Patients and Methods: A total of 45 patients with supratentorial high grade gliomas were included from 2004 to 2007. The treatments were performed in our radiotherapy department. The inclusion/exclusion criteria were: -Anaplastic Astrocytoma (AA) and Glioblastoma Multiforme (GBM) histology. -Karnofsky Performance Score (KPS) 70. -18-65 years old. -Total or subtotal macroscopic surgical resection. -No previous chemotherapy/ inmunotherapy treatment. -Informed consent obtained. 5
Control Group DTT : 60 Gy (2 Gy x 5d / wk during 6 weeks) The total treated volume was: : tumor + oedema +3-4cm of margins 2D Conventional Radiotherapy (local fields) 7
Prospective Group DTT : 66-70 Gy (1,8 Gy x 5d/wk during 7-8 weeks) Treatment Volumes (ICRU 50 & 62): *GTV: enhanced contrast lesion defined by CT or MRI. *CTV 1: enhanced contrast lesion + the perilesional edema + 3-4 cm of margins. *CTV 2: enhanced contrast lesion + 2cm of margins. *PTV 1: CTV1+ + 10-15mm 15mm margins when technique is uncertain. *PTV2: CTV2 + margin of 10-15mm 15mm when technique is uncertain. Level 2 (the( Radiotherapy European Dynarad Consortium) of 3D Conformal 8
2D CONVENTIONAL RADIOTHERAPY. Conventional Simulator (Beam geometry determined by fluoroscopic simulation) Immobilization: Velcro strap, head support 2D treatment planning systems: Theraplan Plus (Basic, non image based) Treatment Machine : Co 60 Theratronics Phoenix 9
3D Conformal Radiotherapy Imaging Equipment (multi-slice CT- Scanner) Immobilization: thermoplastic mask 3D image based treatment planning systems: Theraplan Plus (Advanced) PrecisePLAN V. 2.12 Treatment Machine 2 Elekta Precise linacs (MLC & EPID) Network R&V System and Networking 10
2-D 3-D Treatment portals were determined based on bony landmarks, where the target was the tumor and peritumoral tissue. Critical structures were avoided or not. Limited information was obtained about isodose distributions such as the minimum and the maximum tumor and normal tissues doses received Evaluation plan consisted only in the examination of one or a very few cross-sectional sectional images. 2-D treatment was verified comparing port films with simulator films. Treatment planning is based on 3-D anatomy, designing beam geometries and treatment portals according to the extension of target and risk structures. The plan evaluation was done through the 2D isodose curves for Multiple Plannar Reconstruction (MPR), 3D isosurface and Dose Volumen Histogram (DVH). 3-D treatment is verified comparing DRR (from( the 3D CT data), with the portal images acquired by films or EPIDs. 11
CLASSIFICATION OF CONFORMAL THERAPY ACCORDING TO THE METHODOLOGY AND TOOLS ASSOCIATED WITH EACH STEP OF THE PROCEDURE (IAEA TECDOC 1588)
3D-CRT 1. Patient data acquisition (level 2 reached) Immobilization Imaging system Reference marks for setup Critical organs Inhomogeneities Gross tumour volume-gtv Clinical target volume-ctv Customized thermoplastic masks. Non dedicated, multi-slice CT-scanner Digital fluoroscopic simulator, MR optional (provided by external institution) Radio-opaque opaque marks, ARPLAY frame optional 3D segmentation provided by TPSs Voxel based correction, automated for bone, manual contouring optional Contouring every slice or interpolated. Expanded from GTV using auto-margin tools Internal target volume (ITV) Non relevant for intra-cranial targets 13
3D-CRT Accounting for beam setting uncertainty Type of radiation and beam modifiers Beam incidence Isocentre Beam limiting device PTV CTV margin 2-Beam definition (level 2 reached) 3D margins based on evaluation of setup errors by repeated simulator and portal l images Photon beams, 6 MV, motorized wedges. Several (including non coplanar) beams SAD technique (auto centred on target) Elekta MLCi,, 80 leaves Only setup margins considered, based on immobilization device and verification images 14
3. Dose calculation and optimization (level 2 reached) Calculation model Pencil beam with inhomogeneity Evaluation of treatment plans Treatment plan optimization Isodoses in MPR, isosurface on 3D rendered volumens and DVHs Trial & error, PTV coverage, forward planning 4. Treatment verification and execution (level 2 reached) Verification simulation Immobilization Aids for positioning Patient positioning Verification reference image Record and Verify system Conventional digital views simulator used,, ortogonal Same as during patient date acquisition, Thermoplastic Mask. Isocentre Lasers Displacements from anatomical landmarks DRR and initial Electronic Portal Images Elekta Precise Desktop+iViewGT In vivo measurements PTW Si-diodes 15
3-D CONFORMAL RADIOTHERAPY 16
2D 3D 17
2D Conventional Radiotherapy. 3D Conformal Radiotherapy 18
Fig. 1 Overall Survival Function CNS High Grade Gliomas. INOR 2004-2007 1,0,9,8 Acumulated Survival,7,6,5,4,3,2,1 0,0 0 5 10 15 20 25 30 35 40 TIME (MONTHS) Mean = 15 95% CI (11, 18) months Median= 7 95% CI (5, 9) months
2D RT Mean = 10 95% CI ( 6,13) Median = 6 95% CI (5,7) 3D RT Mean = 18 95% CI (13, 23) Median = 18 95% CI (7, 29)
DISTRIBUTION OF COMPLICATIONS IN PATIENTS RECEIVING 2D AND 3D RT 20 18 F R E Q U E N C Y 16 14 12 10 8 6 4 2 2D 3D 0 COMPLICATIONS
Cox Regression. Prognostic Factors in High Grade Gliomas p Exp(B) Lower 95,0% CI Upper Female 0,004 0,218 0,077 0,614 Age (39-50) 0,259 Age (51-60)) 0,327 2,016 0,496 8,203 Age (61 and older) 0,130 3,306 0,703 15,561 A. A. Histology 0,820 0,894 0,341 2,343 Complete Surgery 0,000 0,110 0,035 0,349 3D RT Technique 0,000 0,085 0,031 0,239 22
RESULTS AND DISCUSSION Median age was 54 years Median survival (Kaplan-Meier method): 3-D D CRT patients: 16 months 2D RT patients: 9 months ( p<0,0001). Survival at 1 and 2 years for 3D group was 51% and 28% respectively; 28% and 16% for 2-D 2 D RT. No significant toxicities were observed, only mild acute. 23
CONCLUSIONS Patients with total resection and 3D CRT had a better median survival. Escalating doses we can increase local control and potentially improve i global survival. It could help to change the treatment approach in some CNS tumours,, attaining a better control and maybe a potential cure. High-dose 3D CRT had a better tolerance and no severe side-effects effects compared to 2D group. There is evidence of a dose-response relationship for hemispheric high grade gliomas. Intensification of local radiotherapy with dose escalation is feasible for some selected patients with GBM or AA. 24
Thank you! 25