THE TRANSITION FROM 2D TO 3D AND TO IMRT - RATIONALE AND CRITICAL ELEMENTS

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THE TRANSITION FROM 2D TO 3D AND TO IMRT - RATIONALE AND CRITICAL ELEMENTS ICTP SCHOOL ON MEDICAL PHYSICS FOR RADIATION THERAPY DOSIMETRY AND TREATMENT PLANNING FOR BASIC AND ADVANCED APPLICATIONS March 27 April 7, 2017 Miramare, Trieste, Italy Yakov Pipman, D.Sc.

The Radiotherapy Process in the beginning Patient Assessment and Decision to Treat with RT Treatment Delivery Target Localization Verification of Patient Position and Beam Placement Define Treatment Calculate Treatment parameters

Radiotherapy 1-D KV therapy for breast

Radiation therapy simulation a note and a diagram in the chart

Radiotherapy 1-D and 2-D

Typical dosimetric calculation = Computation of Beam- ON time for a Co-60 treatment BOT i =PD i /100 x T 100,d,FS

Planning Radiotherapy 1-D + Simple beam arrangements Prescription to a point Calculations Standard condition tables (PDD and BOT) Corrections for SSD and field size Blocked field corrections = > Equivalent Square Point of interest calculations

The Radiotherapy Process in 2-D Patient Assessment and Decision to Treat with RT Data transfer to Treatment Unit Verification of Transferred Treatment Parameters Radiation Therapy Image Acquisition Plan Check Verification of Patient Position and Beam Placement Treatment Planning Field Definitions Beam arrangement Dose Distribution Calculation Plan Approval Treatment Delivery

In 2D radiotherapy The target is defined in relation to anatomic landmarks heavy reliance on bony anatomy The extent of fields is driven by knowledge of anatomy and by disease pathways Extensive use of physical examination, palpation and physical measurements of the patient. Dose distribution information limited to single plane of major significance in order to cover the target. Energy selection is very important. Protection of critical organs set by experience

The Radiotherapy Process in 2D with Radiographic Simulation Patient Assessment and Decision to Treat with RT Block Fabrication Data transfer to Treatment Unit Radiation Therapy Image Acquisition Plan Check Verification of Transferred Treatment Parameters Anatomic measurements and contours Plan Approval Verification of Patient Position and Beam Placement Treatment Volume Localization Treatment Planning Field Definitions Beam arrangement Dose Distribution Calculation Treatment Delivery

Radiotherapy 2-D with R/F simulation Targeting Palpation Use of planar images Reference to Anatomical landmarks No Information on actual volumes Beam s eye-view of simple fields Choice of field size - usually by disease site rules Blocking Protection of critical structures rather than conformality. Based on clinical experience to avoid complications Treatment fields not conformal to target

We never treated our patients with 2D RT Our information was 2D Radiographs collapsed all the anatomy unto a 2D radiographic film We could only represent one plane at a time Our patients? All of them tri-dimensional!

The 90 s the era of 3D Perez and Brady - Principles and Practice of Radiation Oncology-1998, and others

3-D Conformal Radiotherapy (3-D CRT) The design and delivery of radiotherapy treatment plans based on 3-D image data with treatment fields individually shaped to treat only the target tissue

Tools in 3-D planning systems design beam orientations display beam s-eye-views (BEVs) design of beam weights calculate dose distribution throughout patient volume computation of 3-D dose to the PTV and PRV evaluation of the dose plan using dose volume histograms (DVH) evaluation of the biological effect of the plan using tumor control probability (TCP) and normal tissue complication probability (NTCP)

The Radiotherapy Process 3D-CRT Patient Assessment and Decision to Treat with RT 3D dose matrices and statistics DRR for setup and for field verification Treatment Delivery Radiation Therapy Image Acquisition Treatment Planning Plan Evaluation and Approval Verification of Patient Position and Beam Placement Creation of 3D data set Beam Aperture design Plan Check Verification of Transferred Treatment Parameters Target Localization and Delineation Structure Segmentation Block Fabrication or MLC file File Transfer to Accelerator

Immobilization Increasingly Important in 3D-CRT

3D-CRT high quality 3-D imaging used to define : gross tumor volume (GTV) clinical target volume (CTV) planning target volume (PTV) planning organ at risk volume (PRV)

Four fields+ 2 arcs for a small Prostate EBT Total prescription 65 Gy to Isocenter

Green Dose Cloud for four fields plus 2 arcs for the small prostate Isodose is the 65 Gy prescription

Dose Cloud for four fields plus 2 arcs for the same small prostate PTV Isodose is now 97% of isocenter prescription ( 63 Gy)

Same Green Dose Cloud for four fields plus arcs for the LARGE PTV Isodose is 97% of isocenter prescription 63 Gy

Virtual Simulation

Treatment Portal Evaluation Tools Digitally Reconstructed Radiographs (DRR) Port verification films Electronic Portal Imaging Devices (EPID) On Board Imagers (OBI) Port comparison Software

CT guided Conformal Plan One of Six fields Prescription 77.4Gy to PTV

Dose Cloud for a Six Fields CRT Prescription Isodose 77.4 Gy small PTV

Dose Cloud for Six Fields CRT Prescription Isodose 77.4 Gy LARGE PTV

Multimodality image registration Acoustic neuroma not clearly visible on CT image Mass clearly seen on reformatted MRI image after fusion with CT

Multiple beams projected on a surface rendering of the patient facilitate setting the patient up for treatment. The puckered surface represents the mask used to immobilize the patient s head in the correct treatment position. Dosimetric effects caused by couch tops and immobilization devices: Report of AAPM Task Group 176 - Med. Phys. 41 (6), June 2014

Non-coplanar beams (peach and red) aimed at a brain tumor(purple), displayed on a digitally reconstructed radiograph. The brain stem (green) and the optic chiasm (orange) are spared using conformal shaping of the beams

Thyroid Each Beam Shaped to Fit the Target Cross Section Contralateral Lung Ipsilateral Lung Contralateral Breast Ipsilateral Breast Heart TUMOR VOLUME External Beam Arrangement for 3-D conformal PBI

Dose distribution for External 3-D conformal PBI

Cranio- spinal Irradiacion

3 D Conformal RT Essential use of CT information Major increase in the use of CT information enables the construction of volumetric data sets The targets are constructed slice by slice from knowledge of anatomy and by disease pathways but aided by visualization of organs and boundaries between them and the targets. Physical examination, palpation and other tests are complemented with cross sectional images. The fields outlines are conformed to the BEV of the targets Physical measurements of the patient are substituted by digital image measurements tools. The target is still defined in relation to anatomic landmarks significant reliance on bony anatomy. Use of DRR s

3 D Conformal RT cont Dose distribution information expanded to multiple planes Multiple beam directions and non-coplanar arrangements reduce the dependence on beam energy Accounting for dose contributions from other planes is made possible by better beam models. Increased weight given to doses to critical organs New tools required to describe target and critical organ doses (DVH) and for plan evaluation DVH s of critical organs started to generate Organ dose tolerance information and partial volume dose tolerance

Comparative Dose-Volume Histograms Dose escalation for Prostate Ca.

RFS vs. DOSE - RT alone From: M.J.Zelefsky et. al.; IJROBP June 1998

RFS vs. DOSE - RT alone 657 patients treated in 1994-95 From: P. Kupelian et. al.; IJROBP Feb 2005

Dose Response From: G.E.Hanks et. al., IJROBP, June 1998

Morbidity vs. Dose From:G.E.Hanks et. al., IJROBP, June 1998

The drama of Radiotherapy We can give radiation doses so high that they can sterilize any tumor and cure any localized cancer If it were not for those inopportune organs and tissues that get in our way and prevent us from doing the best of jobs

The Radiotherapy Process - IMRT Patient selection Inverse optimization Treatment Delivery plan (dmlc, S&S, etc) Imaging studies Prescription goals Dose distribution calculation Treatment Delivery Immobilization devices Planning of Treatment and at-risk Volumes Plan evaluation and approval Verification of Patient Position and Beam Placement Target definition (anatomy, physiology and the natural history of the disease) Organs at risk delineation Treatment parameter transfer to R&V and to treatment unit control Plan test and verification

Relation between Volumes Margin Sensitive Organ I PTV CTV GTV 50% Sensitive Organ II 95% TREATED VOLUME ICRU-50 and ICRU-62

Structure Definitions Typical of an Head and Neck IMRT Treatment Design DPF, NSUH_LIJ,NY,USA

Uncertainties (ICRU 62) Combined uncertainties to define the PTV from the GTV (A)=linear addition of margins (B)=probabilistic addition of IM and SM (C)=global safety margin (empirical compromise between adequate coverage of GTV and unacceptable irradiation of organs at risk (OARs)

Immobilization is of major importance to reduce setup margins (SM)

The Radiotherapy Process - IMRT Patient selection Inverse optimization Treatment Delivery plan (dmlc, S&S, etc) Imaging studies Prescription goals Dose distribution calculation Treatment Delivery Immobilization devices Planning Treatment and at-risk Volumes Plan evaluation and approval Verification of Patient Position and Beam Placement Target definition (anatomy, physiology and the natural history of the disease) Organs at risk delineation Treatment parameter transfer to R&V and to treatment unit control Plan test and verification

A new perspective on what is the prescription Identification of the Target is a must Definition of the desired Target DVH Determine the desired DVH s for Sensitive Structures Assign Uncertainties to the Volumes Set Goals and Priorities or Penalties

The new fashion in prescriptions

DVH limits reference values Compiled and distributed without warranties - by Nathan Childress, Ph.D., through http://www.medphysfiles.com/

The Radiotherapy Process - IMRT Patient selection Inverse optimization Treatment Delivery plan (dmlc, S&S, etc) Imaging studies Prescription goals Dose distribution calculation Treatment Delivery Immobilization devices Planning Treatment and at-risk Volumes Plan evaluation and approval Verification of Patient Position and Beam Placement Target definition (anatomy, physiology and the natural history of the disease) Organs at risk delineation Treatment parameter transfer to R&V and to treatment unit control Plan test and verification

Inverse Planning Problem Dose to point i: x j D i = x 1 d 1i + + x J d Ji = x d i Objective function: F(x) = w i i (D i - P i ) 2 Minimize F(x): F(x) = 2 w i (D i - P i ) d i = 0 i i organ target

Types of Objective Functions w (D-P ) 2 l l target organ at risk (D-D c ) 2 w (D-P ) 2 u u P l P u D c

Posterior Field Intensity Profile - Prostate

Delivery Methods to Modulate the Intensity Custom physical compensators Sliding Window with d-mlc Step and Shoot with MLC Slit Arc with binary MLC (Tomotherapy) VMAT RapidArc After the optimization all require a final calculation of fluence and dose distribution!

Plan Review GTV (red), CTV (purple), Parotids (tomato), Brain Stem (green) DPF, NSUH_LIJ,NY,USA

Plan Review: Dose Volume Histograms Dose Volume Histograms of the target and critical structures must be reviewed The same as you would for a 3-D plan, but more structures

Do We Deliver the Correct Dose Distribution for Treatment the first time? Associate the d-mlc files to the fields in the Record and Verify system Verify start MLC positions for each field Verify modality and other parameters of each field against the reference plan. Measure the dose distribution (patient specific QA)

Do We Deliver the Correct Fluence for Treatment every time? Periodic QA of the d-mlc Audit the d-mlc motion history for the treatment Audit the patients electronic records

Do We Deliver the Same Treatment Every Time? With an 80 leaf MLC,there are about 2,000 parameters and 15,000 leaf positions per day, that have to be just right. every day. Record and Verify systems should be an integral part of IMRT delivery! http://www-pub.iaea.org/mtcd/publications/pdf/pub1607_web.pdf

Do We Deliver the Correct Dose Distribution for Treatment every time? For many anatomical sites we have limited control of the internal organ motion.

Effects of Intra-Fraction Organ Motion on the Delivery of IMRT with an MLC Conventional treatment Effect of organ motion on GTV is accounted for by PTV, which is always inside the beam aperture. IMRT treatment: summation of small beams No organ motion delivered = planned with organ motion delivered planned Courtesy of Dr C. S. Chui

Targeting Accuracy and Localization Targets Move Patient positioning Limits on delivery system Implication: Increased risk of complications seen with dose escalation Some Solutions Minimize Uncertainty in Target Organ Location, perhaps on a daily basis Use Image guided localization of the target or a reliable surrogate Use gated beam delivery

The great challenge! The better we can fix the target and be sure where we deliver the dose, the more we can reduce the margin required to convert CTV to PTV, and spare dose to sensitive structures! However The tighter the dose distribution, the better we must know where the target is at all times! If not We will achieve the exact opposite of our goal!

AAPM Report No. 82: Guidance Document on Delivery, Treatment Planning, and Clinical Implementation of IMRT. (2003) http://www.aapm.org/pubs/reports/rpt_82.pdf.

TECDOC No. 1588. (2008) www.pub.iaea.org/mtcd/publications/pdf/te_1588_web.pdf

Reference of References The Modern Technology of Radiation Oncology: A Compendium for Medical Physicists and Radiation Oncologists - Volume 3 - J. Van Dyk, editor. Madison, WI: Medical Physics Publishing, (2013) Chapter 16: Radiation Oncology Resources for Working, Teaching, and Learning https://medicalphysics.org/documents/vandykch16.pdf

IMRT is a powerful and sharp tool in the treatment of cancer with radiation! We must use it with great care and respect!!!