IMRT - the physician s eye-view Cinzia Iotti Department of Radiation Oncology S.Maria Nuova Hospital Reggio Emilia
The goals of cancer therapy Local control Survival Functional status Quality of life
Causes of the local failure with conventional RT Radiation resistance of tumor stem cells and clonogens to conventional dose levels of 60 to 70 Gy The radiosensitivity of the surrounding normal tissue limiting the dose to the target
The goal of the radiation oncologist To deliver an effective dose to the tumor To do it without causing severe injuries to adjacent healthy tissue
The Past CT introduction in RT planning The Present?? FIELD FIRST TUMOR SECOND The New Paradigm TUMOR FIRST FIELD SECOND
The Present 3 Dimensional Conformal Radiation Therapy (3DCRT) The 3DCRT is a high definition technique that conforms the spatial dose distribution to 3D target volume while reducing exposure of healthy tissue to a minimum
The Present Intensity Modulated Radiation Therapy (IMRT) Is an advanced form of 3D-CRT in which the beam intensity of each field is modulated in a rather complex way
Intensity Modulated Radiation Therapy Generates dose distributions highly tailored to the shape of the tumor in 3D with steep gradients around it, with reduction of normal tissue high dose irradiation
Benefits of IMRT Allows delivery of conventional doses with decreasing risk of acute and chronic toxicity Reduction of xerostomia (head & neck cancer) Reduction of rectal bleeding (prostate cancer) Allows better coverage of tumor adjacent critical structures
Benefits of IMRT Allows dose escalation without increasing risk of normal tissue damage Allow re-irradiation of locally recurrent tumors
Benefits of IMRT Allows the simultaneous irradiation of multiple targets with different doses per fraction
Benefits of IMRT The inhomogeneity of IMRT can be exploited to accelerate dose fractionation even with once-daily fractionation - SIB Simultaneous Integrated Boost -
Nominal doses corresponding to normalized total doses Target NTD (Gy) Nominal dose in 25fx Nominal dose/fx for 25fx Nominal dose in 30fx Nominal dose/fx for 30fx Nominal dose in 35fx Nominal dose/fx for 35fx Electively treated nodes 50.0 50.0 2.00 54.0 1.80 57.8 1.65 Regional disease 60.0 56 2.24 60.0 2.00 64.0 1.83 Primary 70.0 61.7 2.47 66.0 2.20 70.0 2.00 Primary 80.0 67.3 2.69 71.7 2.39 75.9 2.17 Primary 90.0 73.0 2.92 77.5 2.58 81.8 2.34 Isoeffect calculation utilized α/β= 20 and doubling time =4 day
SMART Simultaneous Modulated Accelerated Radiation Therapy CTV2 CTV1 CTV3 CTV1 CTV2 CTV3 CTV2 CTV3 T2N1 oropharynx 60/2.4Gy CTV1 56.25/2.25Gy CTV2 50/2Gy CTV3
Advantages of SMART More conformal More efficient: same plan for all fractions Shorter treatment duration (fewer fractions) Biologically more effective: higher dose/fx to the target volume Less toxic for normal tissues: higher conformality means lower total dose and lower dose/fx to normal tissues outside the target volumes
The dose-painting Chao IJROBP, 2001 The hypoxia is one of the most important factors affecting the radiation response The knowledge of hypoxic regions allows to plan overwhelming treatment strategies 80Gy/35fx to hypoxic sub-volume 70Gy/35fx to GTV 60Gy/35fx to CTV
IMRT - current status IMRT users are treating a wide variety of disease sites Most common site are head & neck tumors and prostate cancer
Is this enthusiasm truly justified? Dosimetric studies demonstrate that IMRT planning tissue sparing and equivalent (or better) target coverage in nearly all tumor sites Clinical outcome studies demonstrate that IMRT treatment treatment toxicity in a wide variety of tumor site and, in select site, tumor control
IMRT literature While both dosimetric and outcome studies are promising #patients remains small Outcome in most series is short (<24mos) None are randomized Longer follow-up and patients needed to assess the full benefits and risks of IMRT
Approaches to IMRT Devote time and energy A new way to plan and treat patients Requires a major commitment of time and energy IMRT is not a panacea Not the solution to all difficult cases Not all patients should nor can receive IMRT IMRT new problems and challenges
Approaches to IMRT Be flexible IMRT is a work in progress Target design, plan optimization etc have not been standardized for any tumor site What we do today may change tomorrow Take an active approach Experts don t have all the answers Necessity to investigated methods of immobilization, positioning, etc.
1 Positioning and immobilization 2 Image acquisition Chain of IMRT process 3 Structure segmentation 4 IMRT treatment planning and evaluation 5 File transfer and management 7 Position verification 6 Plan validation 8 IMRT treatment delivery and verification
Step 1 Patient Selection Not all patients can nor should receive IMRT Ideal patients Cooperative/not in pain Not too obese Understanding physicians
Ideal sites Irregularly shaped Regular shaped targets are well treated with 3DCRT Immobilizable parts of the body Head/neck > abdomen, pelvis Proximity to critical normal structures Otherwise well treated with 3DCRT Requiring high doses
Step 2 Positioning and immobilization Positioning: should be comfortable due to possibly longer treatment times Immobilization: due to the rapid dose gradients, setup uncertainty must be minimized Success of the IMRT process begins with proper setup and immobilization!
Step 3 Simulation Contrast: recommended (particularly useful in the delineation of lymph node sites) Scanning: image the entire external contour and all the organs of interest!! Without the entire external contour, IMRT planning can not be done Without the entire organ, DVHs can not be calculated nor interpreted
Step 4 Target and tissues delineation Very time-consuming for the physician A gross tumor volume (GTV), clinical target volume (CTV) and all normal tissues have to be contoured on all axial CT slices
GTV Usually the simplest of the two volumes. Sometimes, not so obvious Take advantage of all available imaging studies (MRI, PET etc) Develop a close relationship with the radiology colleagues
If you can t t see it, you can t t hit it. If you can t t hit it, you can t t cure it
CTV The clinician s target volume In some tumors it may be quite simple (e.g. localized prostate cancer) In others, it may be quite complex (e.g. gastric or cervical cancer) Requires considerable knowledge of anatomy, sites of disease spread and patterns of failure
CTV design Decide what to include (GTV + sites A,B,C etc) Decide how to contour them
CTV design Select the sites is only 1/2 the battle! While two physicians may agree on the components of the CTV, they most likely disagree on how to contour them
CTV design
3DCRT: tumoricidal dose coverage goes beyond the target IMRT: tumoricidal doses track targets Target: not delineated, not treated Critical structures: not delineated, not avoided
WHAT TO SHOOT A major potential pitfall of IMRT is the failure to select and delineate the targets accurately
Step 5 Treatment planning Identification of the planning target volume (PTV) The physicist s target volume accounts for patients setup uncertainty and organ motion The PTV is the target that is used in IMRT planning Unless the PTV is covered by the prescription dose, the CTV is not
PTV PTV design is not a trivial process Optimal PTV design requires Knowledge of the clinic s setup uncertainty The impact of internal organ motion PTV normal tissues dose toxicity PTV tumor dose tumor recurrence
Step 5 Treatment planning Dose prescription To define dose-volume constraints for the PTV and normal organs Constraints define desired dose-volume histograms (DVH) for PTV and normal organs Since few physicians think in terms of DVHs, this process can be frustrating
Dose prescription PTV Prescription dose % volume that can receive > prescription % volume that can receive < prescription Minimum and maximum acceptable doses Normal tissues Dose limit % volume that can receive > limit Maximum acceptable dose Don t ask for the impossible!
H&N - OARs constraints spinal cord Dmax < 46 Gy expanded spinal cord Dmax < 50 Gy parotid gland Dmean < 26 Gy or V 30Gy < 50% mandible Dmax < 70 Gy optic pathways Dmax < 56 Gy larynx V 40Gy < 50%
Prostate - OARs constraints rectum V 65Gy <35% and V 70Gy <25% and V 74Gy <5% bladder V 65Gy < 35% femoral heads Dmax< 50 Gy
An inverse planning system tries to give what it thinks is the best answer to the problem we have posed To change the answer, we have to change our question
Step 6 Plan evaluation Requires considerable time and attention A major principle of IMRT is the trade-off between conformity and homogeneity Conformity Homogeneity
Step 6 Plan evaluation Highly conformal plans will thus always include hot and cold spots Three questions to ask about all hot and cold spots Magnitude? Volume? Location?
Step 7 Treatment and follow-up IMRT treatments are more sensitive to geometric uncertainties They introduce sharp gradients near the perimeter of both the PTV and the OARs During a single fraction IMRT techniques treat only a portion of the PTV at any instance IMRT treatments typically take longer than conventional radiation therapy or 3DCRT
Step 7 Treatment and follow-up Look for unexpected side effects Dose is being distributed differently than we are used to, so be alert for possible new toxicities The effect of altered dose fractionation is unknown and potentially dangerous
72 Gy 56.8 Gy Nasopharynx T1N2
54 Gy/2Gy + 26 Gy/2Gy Nasopharynx T1N1
bellagamba LarynxT3N2b 54Gy/2Gy + 26 Gy/2Gy
Larynx T3N2c 66/2.2Gy CTV1 54/1.8Gy CTV2
CTV1o CTV2 CTV2 CTV1h Larynx T1N0 Hypofarynx T1N0 66/2.2Gy CTV1 spinal cord 46Gy 54/1.8Gy CTV2 parotid gland 26Gy
Oropharynx T2N2a (IVA) CTV1 66Gy/2.2Gy CTV2 60Gy/2.0Gy CTV3 54Gy/1.8Gy
CONCLUSIONS The IMRT plan should be sufficiently better to justify the decreased departmental efficiency The IMRT is a high-precision technique and it requires a very rigorous approach throughout the treatment process, from acquisition of anatomic data until the dose delivery
Mistakes happen when you do not look carefully first
Thank you for the attention