Aspetti fisici della radioterapia moderna - II: Agenzia Provinciale per la Protonterapia Trento, Italy Aspetti fisici della radioterapia moderna - II: Treatment planning, IMRT, protoni Marco Schwarz schwarz@atrep.it 23 Settembre 2010

Treatment Planning in 3D CRT

3D CRT Target defined in soft tissues on CT images Higher target/OAR doses than in 2D CRT 3D Treatment planning Safety margins must be considered while designing treatment field ICRU 50(1993) and ICRU 62(1999) set the standard for dose planning and dose reporting reference volumes.

PTV concept: pros CTV = Clinical Target Volume (visible + microscopic disease) PTV = Planning Target Volume Forced people to explicitely incorporate geometrical uncertainties into treatment planning Very appropriate tool for CRT: not too simple, not too complex.

‘Margin recipes’ Analytical solution for spherical targets (van Herk 2000) Derived/verified with simulations for real cases (e.g. Stroom 1999, Van Herk 2002) as a function of population-based data on geometrical uncertainties

Different 'recipes' according to the desired probability level PTV planning= same dose prescription for all points above a given probability of presence for target cell

PTV: cons Use of accurately defined margins still quite rare Dose homogeneity in the PTV became a must more for technical than for clinical reasons N.B. IGRT mostly aims at reducing PTV margins without radically changing PTV-based RT techniques Most important: the PTV concept works only if three assumptions are valid:

PTV - playing by the rules The PTV is a tool for dose planning and dose reporting. There are three underlying assumptions: 1. The dose distribution is invariant for (small) translations and rotations 2. The margins are chosen appropriately as a function of the geometrical uncertainties one wants to compensate for 3. The dose distribution in the PTV is as homogeneous as possible. Condition1 is granted using photons, 2 and 3 must be ensured using correct planning practices.

? + = CTV PTV expansion OAR CTV OAR As if one should prefer homogeneous doses in the wrong PTV instead of heterogenous doses in the right PTV

Treatment planning in IMRT

More degrees of freedom More need to know what you want CRT IMRT

How to tell a machine what we want from it ?

Still struggling with TP in IMRT Inst.1 Inst. 2 Inst. 3 Inst. 4 Inst. 5 Adapted from Das et al, JNCI 2007

In IMRT si hanno molti più gradi di libertà che in CRT, troppi per poter essere gestiti ‘a mano’. Gli scopi del trattamento devono essere espressi in un linguaggio comprensibile tanto dall’uomo quanto dalla macchina L’ottimizzazione in IMRT è la gestione via macchina di una serie di obiettivi intrinsecamente in contraddizione.

Funzione di costo Traduzione quantitativa delle caratteristiche del piano di trattamento in termini di Obiettivi di dose (e.g. Dmin, Dmax) Intenti del trattamento (e.g. controllare la dose vs. massimizzarla/minimizzarla) Trattamenti precedenti Informazioni biologico/funzionali Informazioni geometriche (e.g. errori di set-up) Parametri di erogazione …

The objective cost function 1. Evaluator Quantifies a relevant feature of the plan 2. Modifier A function f of the difference between the actual (E) and the desired (E0) value of the evaluator Dmean Dmin/Dmax DVHpoint # segments treatment time plan robustness …

3-step IMRT treatment planning 1. Fluence optimization Cost function minimization Up to 10^4 ‘beamlets’ Dose calc: fast but not very accurate 2. Segmentation Mechanical and dosimetrical MLC parameters are included Deterioration of the dose distribution 3. Final dose calculation No reoptimization Dose calculations: slower, but more accurate than in step 1.

Aperture based treatment planning 1. Initial fluence optimization 2. Initial Segmentation 3. Tuning of a deliverable plan Taking benefit of degeneracy --> More efficient delivery Less computational burden = Possibility of using accurate dose algorithms

What do we talk about when we talk about ? Patient specific QA

Don’t forget the big picture Huq et al, IJROBP 2008 71(1) Supp.

2-D dosimetry + gamma analysis What is patient specific in this approach? The beam setting Which aspect of the treatment chain is evaluated? The head model In most cases, field by field analysis Some techniques require whole treatment verification (e.g. VMAT)

Monte Carlo dose calculation (Tübingen) Main advantages 1)It solves the main dosimetric problem of IMRT dose calculation algorithms (source model) 2)Combined with hardware QA, it allows to come back to separate hw e sw QA, as in CRT

In-vivo dosimetry(NKI) Planning CT (3D) Planning dose (2D patient mid-plane) select mid-plane slice EPID portal dose (2D imager plane) EPID dose (2D patient mid-plane) back-projection EPID treatment image (2D) -evaluation separate fields, 2D Courtesy B. Mijnheer

Dose-based corrections protocols? Planning CT + Planned dose CBCT + In vivo dosimetry Gamma analysis: dose errors Vs anatomy changes McDermott, R&O2008

Delivery

Delivery

Tecniche ad arco. Perché? Aumento numero di campi >> aumento gradi di libertà Migliore conformazione della dose In caso di target concavi migliore risparmio degli OAR Erogazione più veloce e riduzione movimenti intra-fraction Molti parlano inoltre di migliore efficienza e riduzione MU, ma l’affermazione è discutibile From De Neve, in “Image-guided IMRT”, Springer Ed. 2007

Time/efficiency

Treatment complexity vs monitor unit s=1-Dmax/Dpresc Bakai et al, PMB 2003

2-step IMRT treatment planning 1. Fluence optimization Cost function minimization Up to 10^4 ‘beamlets’ Dose calc: fast but not very accurate 2. Segmentation Mechanical and dosimetrical MLC parameters are included Deterioration of the dose distribution 3. Final dose calculation No reoptimization Dose calculations: slower, but more accurate than in step 1.

Aperture based treatment planning 1. Initial fluence optimization 2. Initial Segmentation 3. Tuning of a deliverable plan Taking benefit of degeneracy --> More efficient delivery Less computational burden = Possibility of using accurate dose algorithms

Author Mu S- IMRT MU VMAT1 Mu VMAT2 MU CRT Time S- IMRT Time VMAT1 Time Vmat2 Palma IJROBP 2008 789 492 454 295 9.6 3.7 Verbakel IJROBP 2009 1108 439 349 Cozzi R&O 2008 479 245 15 1.7 Vanetti R&O 2009 1126 463 584 1.3 Clivio R&O 2009 1531 468 545 9.4 1.1 2.6 Nicolini Rad On 2009 1398 796 11.5 3 Shaffer IJROBP 2009 (E-pub) 363 5.1 1.8 Zhang IJROBP 2009 (E-Pub) 642 290 Shaffer Clin Oncol 2009 1819 949

Tomoterapia seriale/elicoidale Cone Beam Dose erogata in una singola/multipla rotazione del gantry Durante la rotazione la fluenza è modulata: - Variazione forma del campo(movimento lamelle MLC) - Variazione dei pesi dei campi (variazione di intensità) Fan Beam Dose erogata grazie ad un fan beam che ruota continuamente in concomitanza alla traslazione del lettino Durante la rotazione la fluenza è modulata: - Variazione forma del campo - Variazione dei pesi dei beamlets Tomoterapia seriale/elicoidale Tecniche Conformal Arc, AMOA, IMAT, VMAT

IMRT (Angoli fissi) IMAT (Archi multipli) VMAT Single arc

Tomoterapia Il gantry ruota per 360° creando 51 proiezioni Modulazione ottenuta variando il tempo di On/Off per ogni lamella Velocità di rotazione del gantry e tempo di trattamento dipendono da: dose di prescrizione, lunghezza target, dose rate

Single/Few Arc(s) vs TOMO

HT: migliore qualità piani gradiente di dose più elevati Prostata HT e IMAT: distribuzioni comparabili; IMAT: erogazione più veloce IMAT: riduzione dose integrale Canale Anale HT: migliore qualità piani; migliore copertura e omogeneità target; migliore risparmio genitali H&N HT: migliore qualità piani gradiente di dose più elevati Solid line: IMAT

Could we solve it by adding a margin ? Interplay effects Bortfeld et al, PMB 2002 Could we solve it by adding a margin ? No (Not completely) Is it that bad ? It depends

Intrafraction (‘interplay’) effects sw s&s10 s&s20 Jiang et al, PMB 2003

New treatment modalities

Radiation delivery technologies HDR 'Conventional' XRT Tomotherapy IMXT 'Conventional' p+ Heavier ions(?) Tomorrow's ideas

Where would we like to use p+ ? 3DCRT TOMO 10% Dose 35%Dose % Gy IMPT 0% Dose In principle, for all patients In practice, whenever dose sparing at all dose levels could make the difference

The Bragg peak

Protons vs photons – Version 2

Protons vs photons – version 3 1.0 0.4 Fotoni Protoni 0.5 1.0 0.2 1.0

Protons vs photons – version 4 X 3D modulation + Steep dose fall off = More degrees of freedom p+ +

Protoni vs. Fotoni – caso pediatrico IMRT IMPT G. Fava - ATreP

IMRT IMPT

IMRT IMPT Sezione assiale con aree di basse dosi

Dosimetric effects of geometrical uncertainties No errors 5mm setup 5mm setup 10 mm respiration 10mm setup M. Engelsman - MGH

X rays protons

Our choices PT center as the first module of a new public regional hospital Emphasis on availability and clinical usability No significant local development on PT technology Delivery mode: PBS only Interest in patient set up outside the treatment room First treatments: first half of 2013(?)