4D-IMRT. The facts, the needs and the solutions. Adaptive radiotherapy in the head and. neck: what is the clinical significance?

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1 Adaptive radiotherapy in the head and neck: what is the clinical significance? Vincent GREGOIRE, MD, PhD, Hon. FRCR Radiation Oncology Dept. Head and Neck Oncology Program & Center for Molecular Imaging and Experimental Radiotherapy, Université catholique de Louvain, St-Luc University Hospital, Brussels, Belgium Adaptive radiotherapy in the head and neck: what is the clinical significance? The facts, the needs and the solutions Adaptive radiotherapy in the head and neck: what is the clinical significance? 4D-IMRT The Cathedral of Rouen C. Monet, 1894

2 Geometric 4D-IMRT CT MRI (T2) FDG-PET PRE-R/ (Week 2) MVCT WEEK 3 (Week 4) kvct WEEK 5 Vaandering, 2006 Variation in GTVs during RT-CH (70 Gy 3 courses on w1, w4, w7) Variation in therapeutic CTVs during RT-CH (70 Gy 3 courses on w1, w4, w7) GTV N, CT GTV T, CT CTV N 70 Gy, CT CTV T 70 Gy, CT Mean slope: -2.15% / treat day (p<0.05) Medial shift: 0.95mm after 25# (p<0.05) Mean slope: -3.18% / treat day (p<0.05) Lateral shift: 1.26mm after 25# (p<0.05) Mean slope: -1.46% / treat day (p<0.05) Medial shift: 0.91mm after 25# (p<0.05) Mean slope: -2.55% / treat day (p<0.05) Lateral shift: 1.52mm after 25# (p<0.05)

3 Variation in prophylactic tumor CTVs during RT-CH (70 Gy 3 courses on w1, w4, w7) Variation in prophylactic nodal CTVs during RT-CH (70 Gy 3 courses on w1, w4, w7) CTV T 50 Gy, CT Heterolateral CTV N 50 Gy, CT Homolateral CTV N 50 Gy, CT Mean slope: -0.63% / treat day (p<0.05) No shift Mean slope: -0.47% / treat day (p<0.05) No shift Mean slope: -0.41% / treat day (p<0.05) Medial shift: 1.76mm after 25# (p<0.05) Variation in parotid volumes during RT-CH (70 Gy 3 courses on w1, w4, w7) Homolateral parotid Heterolateral parotid Variation in parotid and TV during RT Authors Imaging Parotid Gland Target Volume COM Volume COM Volume Mean slope: -0.93% / treat day (p<0.05) Medial shift: 3.21mm after 25# (p<0.05) Mean slope: -1.03% / treat day (p<0.05) No shift Barker, 2004 EXaCT 3.1 mm 0.6% / day 3.3 mm 1.8% / day medial Hansen, 2006 kvct % % - - at 36 Gy Robar, 2007 kvct mm 4.9% / week - - / w Han, 2008 MVCT - 1.1% / day - - Vasquez- Osorio, 2008 kvct 3 mm medial 17% loss at 46 Gy - -

4 Impact on dose distribution 0 14Gy 14 25Gy 25 35Gy 35 45Gy 45 69Gy Classic CT-based planning Adaptive PET-based planning + + w2 w0 w3 w0 SIB-IMRT 30x2.3 Gy 30x1.85 Gy + + w4 w0 w5 w0 Total Dose really received by each volume element of the patient Planning Classic CT-based Adaptive CT-based Classic PET-based Adaptive PET-based V 10 99% 99% 99% V 50 99% V 80 98% 98% V 90 85% 83% 73% V 95 80% 82% 67% P<0.001 V % 81% 58% Geets, 2007 Dose distribution after adaptive RT-CH (n=5) Biological heterogeneity Homolat Parotid D mean (Gy) Heterolat Parotid D mean (Gy) SC D 2 (Gy) Larynx D 5 (Gy) Oral cavity D mean (Gy) Mandible D 2 (Gy) Homolat Submax gl D mean (Gy) Heterolat Submax gl D mean (Gy) «Classical» «Classical» «Real» «Real» Adaptive Adaptive CT-based PET-based CT-based PET-based CT-based PET-based [ 18 F]-FDG TEP Registered autoradiography Skin V 65Gy (cc) V 95% (cc) Résolution 2.3 mm Résolution 0.1 mm N. Christian, 2007

5 Dose painting by number Flat dose Survival is non-flat (higher in resistant areas) Mean Tumor Dose = 2 Gy Far more efficient use of dose Non-flat dose More similar survival across entire tumor Adaptive radiotherapy in the head and neck: what is the clinical significance? Courtesy of D. De Ruysscher Tumor Control Probability (TCP) Dose-response curve for neck nodes 3 cm 120 Complication probability after parotid gland irradiation Complication = stimulated flow rate 25% of the pre-rt rate at 12 months Tumor control (%) , Total dose (Gy) Bataini et al, 1982 From Eisbruch, 1996

6 Clinical impact of the TLD QA program of the EORTC assessed by biological modeling HeadSTART trial: OS (analysis by ITT) 65 high-energy treatment units have been checked : 22 underdosing 41 overdosing 3.3% 7% loss of local control 10% 23.7% excess mild to moderate complications Bentzen, R & O, 48 (S1): 728, 1998 Peters, 2009 HeadSTART trial: DFS as a function of compliance to protocol HeadSTART trial: LR-DFS for the compliant patients Patients who had received at least 60 Gy of RT to PTV Patients who had received at least 60 Gy of RT to PTV % alive and failure-free Compliant/No mod Compliant/Mod Non-compliant/No TCP dev Non-compliant/TCP dev % locoregional failure-free CIS CIS/TPZ Hazard ratio 95% CI 10 P < P = Years from end of RT Years from end of RT Peters, 2009 Peters, 2009

7 Adaptive radiotherapy in the head and neck: what is the clinical significance? A clinical trial? IMRT >< geometrical adaptive IMRT? Geometric adaptive IMRT >< biological adaptive IMRT? Site / TNM stage PTV2 PTV3 PTV4 PTV5 PTV2 PTV1 PTV1 PTV1 PTV1 But still a long way to go My vision of Radiation Oncology in 2009 and beyond RO will be (even more) multidisciplinary RO will be conformal (e.g. IMRT, proton, hadrons) RO will be tailored (based on imaging and molecular profiling) and adaptive RO will be associated with targeted agents Harari et al., 2005

8 Challenges in Head & Neck loco-regional treatment The reality Image-Guided Radiation Therapy in HNSCC Adaptive IMRT: geometrical, biological & dosimetrical which imaging modalities?? The Bridge at Argenteuil which biological pathways?? which volume/dose registration algorithms?? how frequently?? C. Monet, 1874 Acknowledgements Communication and Remote Sensing Lab. Adriana PARRAGA, Eng. Benoit MACQ,Eng., Ph.D. ENT and Head & Neck surgery Imaging Marc HAMOIR, M.D. Emmanuel COCHE, M.D. Thierry DUPREZ, M.D. Max LONNEUX, M.D. Oral & Maxillo-Facial surgery Pierre MAHY, M.D. Hervé REYCHLER, M.D., D.M.D. Pathology Birgit WEYNAND, M.D. PET laboratory Anne BOL, Ph.D. Daniel LABARE, Ph.D. Radiation Oncology Nicholas CHRISTIAN, M.D. Pierre CASTADOT, M.D. Xavier GEETS, M.D., Ph.D. John LEE, eng., Ph.D. Pierre SCALLIET, M.D., Ph.D. My vision of Radiation Oncology in 2009 and beyond

9 Challenges in Head & Neck loco-regional treatment Target selection and delineation Adaptive IMRT: geometrical, biological & dosimetrical which imaging modalities? which biological pathways? which volume/dose registration algorithms? how frequently? Concomitant association with drugs and/or small molecules H&N IMRT practice heterogeneity among Dutch Radiation Oncologists Rasch et al., 2007 Tumor Control Probability (TCP) Geometric 4D-IMRT Alternate week MVCTs: CTV-PTV s Effect E ΔE ΔD CTV to PTV 18,00 16,00 14,00 12,00 10,00 8,00 6,00 4,00 2,00 0, ,00 12,00 10,00 8,00 6,00 4,00 2,00 0,00 Medio-lateral direction Antero-posterior direction Initial CTV- PTV Corrected CTV-PTV 4m m Initial CTV- PTV Corrected CTV-PTV 4m m 14,00 12,00 10,00 8,00 6,00 4,00 2,00 0,00 Cranio-caudal direction Initial CTV- PTV Corrected CTV-PTV 4m m 75 patients total of 1481 MVCT CTV-PTV: (2*Σ + 0.7σ) D Dose Vaandering, 2007

10 Parotid gland sparing in IMRT for HNSCC Parotid gland sparing in IMRT for HNSCC Parotid gland sparing in IMRT for HNSCC