Pet And Radiotherapy For Head And Neck

PET and Radiotherapy for Head and Neck Cancer: today and tomorrow… Vincent GREGOIRE, M.D., Ph.D. Head and Neck Oncology Program, Radiation Oncology Dept., & Center for Molecular Imaging and Experimental Radiotherapy, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium MAESTRO Jan. 2007

Potential added-value of PET in oncology S / RxTh / CH Work-up-staging prognostic evaluation GTV/CTV Selection/delineation Functional Image-guided IMRT Early response FDG evaluation C-methionine EF3 - F-miso - CuATSM Final response BFU - FLT evaluation … Early detection of recurrence MAESTRO Jan. 2007

Imaging in radiotherapy: … today and tomorrow … • Selection of Target Volumes with FDG-PET • Delineation of GTV with FDG-PET • Selection / delineation of CTV MAESTRO Jan. 2007

The use of FDG-PET for the selection of Target Volume: setting the scene Laryngeal SCC: T2-N1-M0 Q: unilateral vs bilateral neck irradiation? A: highly sensitive examination MAESTRO Jan. 2007

Detection of metastatic disease in the neck • N=106 patients • oral cavity tumors • Neck dissection for all patients (2196 lymph nodes) Sensitivity Specificity Accuracy NPV PPV PET 70% 82% 75% 71% 81% CT 66% 69% 70% 66% 74% MRI 64% 69% 66% 62% 71% US 84% 68% 76% 79% 75% MAESTRO Jan. 2007 Stuckensen et al., 2000

Potential added-value of PET in oncology Comparison between CT and FDG-PET for nodal staging. Site Sensitivity Specificity CT FDG-PET CT FDG-PET Head and neck cancer 36-86% 50-96% 56-100% 88-100% NSC lung cancer 45% 80-90% 85% 85-100% Cervix carcinoma 57-73%1 75-91% 83-100%1 92-100% Esophageal cancer 11-87% 30-78% 28-99% 86-98% 1 CT or MRI MAESTRO Jan. 2007 Grégoire, 2004

Potential added-value of PET in oncology Comparison between PET and PET/CT for N staging (n=260) Sensitivity (%) Specificity (%) PPV NPV PET/CT 92 93 88 94 PET+CT 88 89 83 92 PET 85 88 82 90 CT 64 83 70 79 MAESTRO Jan. 2007 Antoch et al., 2004

Target MAESTRO Jan. 2007 J. John, 1974

The Gross Tumor volume (GTV) MAESTRO Jan. 2007 Daisne et al., Radiology, 233: 93-100, 2004

The Gross Tumor volume (GTV) MAESTRO Jan. 2007 Daisne et al, 2004

From PET image to tumor: a fixed threshold? GTV (ml) Patient Surgical 40% 50% Specimen 1 8.3 23.3 11.8 55.1 2 5.2 10.9 6.7 55.7 3 30.9 29.7 21.7 38.6 4 4.1 8 5.3 57 5 5.6 37.9 19.2 70.9 6 8.6 9.7 6.6 43.2 7 17.3 35.9 25.5 59 8 15.4 41.8 28.3 67.5 9 24.3 39.9 30 56.5 mean 13.3 26.5* 17.2 55.9 MAESTRO Jan. 2007 Geets et al, 2006

Functional imaging and automatic segmentation Volume delineation based on automatic thresholding with 18F-FDG MAESTRO Daisne et al, 2003 Jan. 2007 Geets et al, 2004

Imaging modalities, TVs and dose distribution MAESTRO Jan. 2007

Image-Guided Radiation Therapy in HNSCC Impact of imaging modality on CTV/PTV delineation Larynx/hypopharynx (n=9) Oropharynx (n=10) 200 Average (± sem) volume (cc) CT-scan 250 CT-scan Average (± sem) volume (cc) FDG-PET FDG-PET 150 200 ANOVA: p<0.05 ANOVA: p<0.01 150 100 100 50 50 0 0 GTV CTV PTV GTV CTV PTV MAESTRO Jan. 2007 Geets et al, 2003

Image-Guided Radiation Therapy in HNSCC Impact of imaging modality on dose distribution MAESTRO Jan. 2007 Geets et al, 2006

Conformal radiotherapy and IMRT in Head and Neck Tumors DAHANCA: http://www.dshho.suite.dk/dahanca/guidelines.html EORTC: http://www.eortc.be/home/ Radio/EDUCATION.htm MAESTRO RTOG: http://www.rtog.org/hnatlas/main.htm Jan. 2007

CT-based delineation of lymph node levels in the neck: Brussels- Rotterdam consensus guidelines Level II Ant. submandibular gland post. belly of digastric m. Post. sternocleidomastoid m. LII Lat. sternocleidomastoid m. Med. paraspinal m. int. carotid artery LV Cra. lateral process of C1 Cau. hyoid bone MAESTRO Jan. 2007

Imaging in radiotherapy: … today and tomorrow … • Atlases • Adaptive Target Volume delineation • Non-rigid registration • Adaptive dose distribution • Other PET tracers MAESTRO Jan. 2007

H&N IMRT practice heterogeneity Atlases? MAESTRO Jan. 2007 Harari et al., 2005

CT MRI (T2) FDG-PET PRE-R/ (Week 2) WEEK 3 (Week 4) WEEK 5 MAESTRO Jan. 2007

Biological adaptive IMRT Before R/ Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 R/ start Images acquisitions CT MR T2 FS MR T2 FDG-PET Anatomic imaging Dynamic FDG-PET • 10 patients with stage III-IV pharyngo-laryngeal SCC treated by CT -RT • Images acquired before R/ and during RT after means doses of 14, 25, 35 and 45 Gy. MAESTRO Jan. 2007 Geets, 2006

PET image segmentation during RxTh UG 4mm Raw image SBR Image processing Image segmentation MAESTRO Jan. 2007 Lee & Geets 2006

PET image segmentation during RxTh UG 4mm SBR Raw image Image processing Image segmentation BG 6mm + deconvolution W&C MAESTRO Jan. 2007 Lee & Geets 2006

PET image segmentation Patient Surgical Threshold- Gradient-based No specimen based method method  Phantom images 1 4.1 8.7 4.7  Synthetic phantom images 2 5.2 7.4 5.5  Jaszczak phantom (6 spheres) 3 5.6 16.3 8.2  Patient images 4 15.4 37.2 19.7  Total laryngectomy 5 17.3 35.4 25.3 (surgical specimen is frozen, frozen, 6 24.3 34.1 25 sliced, 7 30.9 33.4 27.8 digitized, delineated, and registred) mean 14.7 24.7* 16.6** * in comparison with surgical specimens, p = 0.014 (Student’s t-test) ** in comparison with surgical specimens, p = 0.19 (Student’s t-test) MAESTRO Jan. 2007 Lee & Geets 2006

Impact on TV delineation P<0.001 MAESTRO Jan. 2007 Geets, 2006

Impact on TV delineation Classic CT-based planning Adaptive PET-based planning P<0.001 Planning V10 V50 V80 V90 V95 V100 Classic CT-based 100% 100% 100% 100% 100% 100% Adaptive CT-based 99% 100% 100% 85% 80% 66% Classic PET-based 99% 99% 98% 83% 82% 81% Adaptive PET-based 99% 100% 98% 73% 67% 58% MAESTRO Jan. 2007 Geets, 2006

Image registration… Reference image Rigid registration Non-rigid registration MAESTRO Loeckx & Maes Jan. 2007 ESAT, 2004

Image registration… Week 0 Week 3 30 Gy SIB MAESTRO Jan. 2007 Parraga, Castadot & Lee, 2006

Image registration… Differential dysplay MAESTRO Jan. 2007 Parraga, Castadot & Lee, 2006

Image registration… Week 3 Week 3 on week 0 Non-rigid Registration (Samba) MAESTRO Jan. 2007 Parraga, Castadot & Lee, 2006

Dose registration… Time 1 (t1) Deformed checkerboard showing the non- rigid Deformed dose at t1 transformation from t1 to t2 Deformed contour on CT at t2 Time 2 (t2) MAESTRO Jan. 2007 Lee, 2006

Other PET tracers… Hypoxia: 18F-EF3 Metabolism: 18F-FDG 11C-Met Proliferation: 76Br-BFU MAESTRO Jan. 2007

From microscopy to PET images… CT-scan MRI µPET-scan Autoradiography MAESTRO Jan. 2007 N. Christian, 2006

Conclusions: future challenges … • Target Volume selection and delineation • Adaptive IMRT: geometrical, biological & dosimetrical •which imaging modalities?? •which biological pathways?? •which volume/dose registration algorithms?? •how frequently?? • Clinical validation MAESTRO Jan. 2007

Acknowledgements • Communication and Remote Sensing Lab. Alois du BOIS d’AISCHE, Eng. Pierre-François d’HAESE, Eng. Benoit MACQ,Eng., Ph.D. • ENT and Head & Neck surgery Marc HAMOIR, M.D. Philippe ROMBAUX, M.D. • Imaging 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. Jean-François DAISNE, M.D., Ph.D. Xavier GEETS, M.D. John LEE, eng., Ph.D. Pierre SCALLIET, M.D., Ph.D. MAESTRO Jan. 2007 Milan TOMSEJ, M. Sc.

Acknowledgements • KULeuven, Radiation Oncology Karin HAUSTERMANS, M.D., Ph.D. Sarah ROELS, M.D. Tom DEPUYDT, Ph.D. Pieter SLAGMOLEN, Eng. • KULeuven, ESAT Frederic MAES, Eng., Ph.D Frederic LOECKX, Eng. MAESTRO Jan. 2007

Target selection and delineation Betrayal of images This is not an apple… R. Magritte MAESTRO Jan. 2007

MAESTRO Jan. 2007 R. Wouters, 1915

Image-Guided Radiation Therapy in HNSCC Impact of imaging modality on dose distribution CT-based target volume FDG PET-based target volume MAESTRO Jan. 2007

IMRT in Head and Neck Tumors Left parotid Hypopharyngeal SCC PTVs T4-N0-M0 Dose: 25 x 1.8 Gy bid Spinal cord Right parotid MAESTRO Jan. 2007

Watershed & Clustering segmentation 1.Raw images 2.Image denoising 3.Image deblurring 4.TAC distances c/s c/s c/s Bil. PSF XYZ D T XYZ XYZ T Image improvement 5.Watersheds D XYZ 9.Segmented images 8.Cluster Analysis 7.TAC distances 6.Wat.sh. mean TACs c/s c/s XYZ D T T T MAESTRO Jan. 2007

Image-Guided Radiation Therapy in HNSCC The 4th dimension … FDG-PET 0 Gy 50 Gy MAESTRO Jan. 2007 Geets et al, 2003

Bayesian terminology for diagnostic imaging studies Disease status “-” “+” Test “-” TN FN NPV = TN/TN+FN “+” FP TP PPV = TP/TP+FP Sensitivity = TP/TP+FN Specificity = TN/TN+FP Disease Disease “-” “+” “-” “+” “-” 48 2 NPV = 96% “-” 25 25 NPV = 50% Test “+” 20 30 PPV = 60% Test “+” 4 46 PPV = 92% Sensitivity = 94% Sensitivity = 65% MAESTRO Specificity = 70% Specificity = 86% Jan. 2007

From microscopy to PET images… Mean minimal distance Mean angle (°) between two skew lines MR-CT: 0.21 0.06 mm 2.23 0.31 PET-CT: 0.23 0.11 mm 2.52 0.74 PET-MR: 0.28 0.07 mm 2.47 0.46 PET-AR: 0.18 0.04 mm 3.53 0.39 MAESTRO Jan. 2007 N. Christian, 2006

Work in progress: other tracers… PET-FLT FLT ? FDG 0 Gy 20 Gy Before surgery MAESTRO Jan. 2007 Lee & et al, HaustermansGeets 2006

Gradient Intensity Image Image saturation (window level) Raw image Grad. Int. image MAESTRO Boundaries do not move! Lee & Geets 2006 Jan. 2007

Pet And Radiotherapy For Head And Neck

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