April 2008 An Introduction to Head & Neck Radiotherapy. 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 April 2008 Myths and facts in Oncology: the challenge of local therapies Chemotherapy Surgery Surgery + radiotherapy Radiotherapy not cure (local recurrence) not cure (distal recurrence) 37% 18% 5% 22% 6% 12% April 2008 Myths and facts in Oncology: the challenge of local therapies in …HNSCC… Chemotherapy Surgery Surgery + radiotherapy ± chemo/biological modifiers Radiotherapy ± chemo/biological modifiers not cure (local recurrence) not cure (distal recurrence) ≈10-15% ≈25-35% 0% 22% >6% >>12% April 2008 Bataini et al, 1982 , 45 55 65 75 85 95 Total dose (Gy) 0 20 40 60 80 100 120 Tumor control (%) Dose-response curve for neck nodes ≤ 3 cm Tumor Control Probability (TCP) April 2008 Human Monkey Baumann et al., Strahlenther Onkol 170: 131-139, 1994 Normal Tissue Control Probability (NTCP) April 2008 Unacceptable normal tissue damage Tumour control Uncomplicated tumour control Effect Dose Uncomplicated tumor control: Therapeutic Ratio
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April 2008
An Introduction to Head & Neck Radiotherapy.
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
April 2008
Myths and facts in Oncology: the challenge of local therapies
Chemotherapy
Surgery
Surgery + radiotherapy Radiotherapy
not cure (local recurrence)
not cure (distal recurrence)
37%
18%
5%
22%
6% 12%
April 2008
Myths and facts in Oncology: the challenge of local therapies in …HNSCC…
Chemotherapy
Surgery
Surgery + radiotherapy ± chemo/biological
modifiers
Radiotherapy ± chemo/biological
modifiers
not cure (local recurrence)
not cure (distal recurrence)
≈10-15%
≈25-35%
0%
22%
>6% >>12%
April 2008 Bataini et al, 1982
, 4 5 5 5 6 5 7 5 8 5 9 5
T o t a l d o s e ( G y )
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
Tum
or c
ontro
l (%
)
Dose-response curve for neck nodes ≤ 3 cm
Tumor Control Probability (TCP)
April 2008
Human Monkey
Baumann et al., Strahlenther Onkol 170: 131-139, 1994
Normal Tissue Control Probability (NTCP)
April 2008
Unacceptable normal tissue damage
Tumour control
Uncomplicated tumour control
Effe
ct
Dose
Uncomplicated tumor control: Therapeutic Ratio
April 2008
Unacceptable normal tissue damage
Tumour control
Uncomplicated tumour control
Effe
ct
Dose
Uncomplicated tumor control: Therapeutic Ratio
April 2008
Unacceptable normal tissue damage
Tumour control
Effe
ct
Dose
Uncomplicated tumour control
Uncomplicated tumor control: Therapeutic Ratio
April 2008
n = 1 2 5 10 20
Total dose (Gy)
Less effect per gray at low doses/#
N = 1
April 2008
“Typical” dose per fraction • 1.8-2 Gy for standard
fractionation
• 1.1-1.3 Gy for hyper-fractionation
Fractionation sensitivity
Withers et al, 1983
Acute effects + tumor response
Late effects
April 2008
Hyperfractionation�Decreased dose per fraction
Conventional fractionation
Hyperfractionation (“pure”, SFD)
Hyperfractionation (“dose escalated”, MFD)
Hyperfractionation (“pure”, MFD)
2.0 Gy/ f, 1x/ d�6 weeks= 60 Gy
1.0 Gy/ f, 2x/ d�6 weeks= 60 Gy
1.2 Gy/ f, 2x/ d�6 weeks= 72 Gy
1.5 Gy/ f, 1x/ d�6 weeks= 60 Gy
April 2008
Oropharyngeal Ca T2-3, N0-1
Years
LOCAL CONTROL SURVIVAL
Years
EORTC Hyperfractionation trial in oropharynx cancer
Horiot 1992
80.5 Gy - 70 fx - 7 wks vs 70 Gy - 35-40 fx - 7-8 wks
p = 0.02 p = 0.08
April 2008
TCD
50 (G
y) Tclon= 9.8d [0;21] Tclon= 3.4d
[1.7;5]
Day 22 [13;30]
Radiobiological hypoxia
Tage nach 1. RT 10 20 30 0
0
60
120
RDI pAB
Petersen et al., IJRB 79: 469-477, 20030
EGF-Receptor
EGFR and repopulation during RT FaDu hSCC
April 2008
Influence of overall treatment time on HNSCC local control
Radiobiological and clinical issues in IMRT for HNSCC
Withers et al, 1988
April 2008
Accelerated fractionation (AF) Shortened overall treatment time, dose per week > 10 Gy
Expectations: • Increased tumor control • Increased early reactions • Unchanged or decreased�
late damage �(AF/HF and/or reduced�total dose) AF/HF
Stratify by Karnofsky score: 90-100 vs. 60-80 Regional Nodes: Negative vs. Positive Tumor stage: AJCC T1-3 vs. T4 RT fractionation: Concomitant boost vs. Once daily vs. Twice daily
Arm 2 (RT+E) Radiation therapy + Cetuximab, weekly
EGF-R inhibitor and RxTh in HNSCC�Phase III Study Design
R A N D O M I Z E
Arm 1 (RT) Radiation therapy
Bonner, 2004 April 2008
Efficacy
Locoregional Control
Overall Survival
Erbitux + RT
Erbitux + RT
RT
RT
Log-rank p
Bonner, 2004
April 2008
Image-Guided Radiation Therapy in HNSCC
1900
1937 1963
1976 April 2008
Image-Guided Radiation Therapy in HNSCC
2000 Intensity Modulated Radiation Therapy
(IMRT)
April 2008
April 2008
(1) Eisbruch 1999, Dawson 2000: University of Michigan (U-M) (2) Lee 2002: University of California at San Francisco (UCSF) (3) Claus 2002, Duthoy 2003: Ghent University Hospital (GUH) (4) Chao 2003: Washington University, St. Louis (WU)
U-M (1) Oral cavity Oro- hypopharynx Larynx
UCSF (2) Nasopharynx
GUH (3) Nasal cavity
Paranasal sinus
WU (4) All sites
CUP
Clinical outcome of IMRT in head and neck cancer
April 2008
April 2008
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
0 1 2 3 4 5 6 7 8 9 10 Deviation from the isocenter (mm)
Cum
ulat
ive
inci
denc
e
Head (3-5 FP)
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
0 1 2 3 4 5 6 7 8 9 10 Deviation from the isocenter (mm)
Cum
ulat
ive
inci
denc
e
Neck (3-5 FP)
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
1
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Deviation of the isocenter (mm)
Cum
ulat
ive
inci
denc
e Shoulder (4 & 5 FP)
April 2008
Image acquisition • Dual detector spiral CT
• 2.7 mm collimation, pitch 0.7, reconstruction of 2 - 2.5 mm
• Display matrix of 512 x 512 pixels
• Contrast enhancement (interstitial and blood vessel contrast)
April 2008
Conformal radiotherapy: 3D reconstruction
April 2008
Conformal radiotherapy: image display
April 2008 ICRU report 62, 1999
• Gross Tumor Volume: GTV
• Clinical Target Volume: CTV
• Planning Target Volume: PTV
Target volumes in Radiation Oncology: ICRU definition
• Organs at Risk: OAR
• Planning Organ at Risk Volume: PRV
April 2008
Conformal radiotherapy and IMRT in Head and Neck Tumors
April 2008
State of the art • Predictive pattern of lymph node involvement in
HNSCC
• Selective neck treatment (irradiation or dissection) for selected N stage
Definition of the extend of the CTV in the neck
April 2008
Incidence of pathologic lymph node metastasis in oropharyngeal tumors
N0-N1 (Ib1)-II-III-IV + RP for post. II-III-IV + RP for post. pharyngeal wall tumor pharyngeal wall tumor
N2a-N2b Ib-II-III-IV-V +RP II-III-IV + RP for post. pharyngeal wall tumor
N2c According to N stage on According to N stage on each side of the neck each side of the neck
N3 I-II-III-IV-V +RP ± adjacent II-III-IV + RP for post. structures according to clinical pharyngeal wall tumor and radiological data 1Ib only if extension to oral cavity