An Introduction to Head & Neck Radiotherapy. Gy - 70 fx - 7 wks vs 70 Gy ... Claus 2002, Duthoy...
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Transcript of An Introduction to Head & Neck Radiotherapy. Gy - 70 fx - 7 wks vs 70 Gy ... Claus 2002, Duthoy...
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
54Gy/ 3x1.5Gy/ ti=6h/ 12d
70Gy/ 2.0 Gy/ 7w CF
70Gy/ 2.0 Gy/ 5w CB
April 2008
DAHANCA 6&7 - H&N SCC - stage II-IV (n=1476)
Overgaard et al. Lancet, 2003
IIIIII IIIIII IIIIII IIIIII IIIIII IIIIII 64-68 Gy/ 2.0 Gy/ 5.5w
IIIII IIIII IIIII IIIII IIIII IIIII IIII 64-68 Gy/ 2.0 Gy/ 6.5w
April 2008
H&N SCC: MACH-NC
Pignon, Lancet, 2000 April 2008
c 1x
3x SD18Gy
18Gy + 1x
18Gy + 3x
Milas et al. Clin Cancer Res 6: 701-708, 2000
RT SD/1xC225 SD/3xC225
Nasu et al., IJROBP 51: 474-477, 2001
C225 anti EGFR Ab; A 431 tumours:
April 2008
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
2%
2% 25%
19%
8%
Clinically N0 neck (n=48)
From Candela, 1990
Clinically N+ neck (n=165)
9%
15% 71%
42%
27%
April 2008
Oropharyngeal Carcinoma Stage Ipsilateral neck Controlateral neck
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
Grégoire et al., 2000 April 2008
DAHANCA: http://www.dshho.suite.dk/dahanca/guidelines.html EORTC: http://www.eortc.be/home/ Radio/EDUCATION.htm RTOG: http://www.rtog.org/hnatlas/main.htm
Conformal radiotherapy and IMRT in Head and Neck Tumors
April 2008
Ant. symphysis menti / platysma Post. hyoid bone / submandibular
gland Lat. ant. belly of digastric m. (Ia) mandible / platysma (Ib) Med. ant. belly of digastric m. (Ib) Cra. geniohyoid m./mandible (Ia) mylohyoid m,
submandibular gland (Ib) Cau. hyoid bone
Level Ia and Ib
RP
LII
LIb
LIa
CT-based delineation of lymph node levels in the neck: Brussels- Rotterdam consensus guidelines
April 2008
Ant. sternohyoid m./ sternocleidomastoid m.
Post. sternocleidomastoid m. Lat. sternocleidomastoid m. Med. paraspinal m. int. carotid artery Cra. hyoid bone Cau. cricoid cartilage
Level III
LV
LIII
CT-based delineation of lymph node levels in the neck: Brussels- Rotterdam consensus guidelines
April 2008
Mr H. D. (77 years): T3-N0-M0 base of tongue (ICD0-10: C01)
April 2008
Rx 6 MV 40 Gy
Rx 6 MV 30 Gy
Rx 6 MV 50 Gy
Elect 8 MeV 10 Gy
“Antique” (7 fields)
April 2008
Rx 6 MV 50 Gy
“Art nouveau” (10 fields, 12 segments )
Ant. RPO LPO
SRAO SLAO
…
Post. Seg. 1 Post. Seg. 2
April 2008
Rx 6 MV 20 Gy
“Art nouveau” (11 fields, 12 segments )
Ant. RAO LPO
LAO1 LAO2
April 2008 April 2008
April 2008
Forward planning IMRT
• « human optimization »
Inverse planning IMRT
• Dose-volume constraints & weights for PTV and OARs
• optimization algorithms
• Penalty function
April 2008
Spare cord Spare left parotid 15 segments 10 levels
1 6. Cummulative % of MUs Segment #
Courtesy of C. Field
April 2008
PTVs
Spinal cord
Left parotid
Right parotid
Hypopharyngeal SCC T4-N0-M0 Dose: 25 x 1.8 Gy bid
April 2008
Left parotid ADC Dose: 30 x 2.0 Gy
PTV
Right parotid
Spinal cord
Inner ear
April 2008
Objective assessment
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Bilateral irradiation Unilateral irradiation
R= 0,77
Max
imum
secr
etio
n (%
)
Mean parotid dose (Gy) April 2008
Subjective assessment
0
2
4
6
8
10
12
0 10 20 30 40 50 60 70
Bilateral irradiation Unilateral irradiation
R= 0,63
SOM
A sc
ale
(arb
itrar
y un
its)
Mean parotid dose (Gy)
April 2008
• 88 patients irradiated with parotid sparing • saliva flow rates for 152 parotid glands • dose / volume / function relationships
• parotid mean dose < 26 Gy is planning goal • Lyman NTCP: n = 1, m = 0.18, TD50=28.4 Gy
Oral cavity, oro- hypopharynx, larynx parotid-sparing 3D-CRT
12/58 patients developed recurrences: 10 in GTV region 2 in elective region (1st echelon)
Limits: local control in GTV area
April 2008 Lee et al. IJROBP 53: 12-22, 2002
Nasopharynx
• 67 patients treated April 1995-October 2000
• Stages I (n=8); II (n=12); III (n=22); IV (n=25)
• Non-keratinizing (n=34); undifferentiated (n=33)
• IMRT by compensators, MLC or MIMiC
• Conventional fields to treat the neck
4-year actuarial distant metastasis-free rate: 66%
Limits: distant metastasis rate
April 2008
-Number of patients 44 -R0 surgery 44 - Male/female ratio 9/1 - Median age at diagnosis 60 years [30-76] - Subsite
Ethmoid sinus 33 (75%) Maxillary sinus 6 (14%) Nasal cavity 5 (11%)
W. Duthoy, 2003
Paranasal sinus
Limits: local control in T4(b)
Complications of postoperative radiation therapy for ethmoid sinus tumors
period 1985 - 1994 1995 - 1998 1999 - 2002
RT 2D 3D
IMRT
PTS 19 11 33
Optic neuropathy
0 2 0
Dry eye syndrome
5 2 0
April 2008
April 2008
Duration of treatment planning procedure 2D planning Forward planning Inverse planning (St-Luc) (Edmonton Cancer center)
Volume delineation 0 - 0.25h 2 - 3h 1 - 1.5h
Planning 0.25h 2 - 8h 1 - 2h
Individualized QC 0h 0.25h 1h
Treatment (per session) 10 - 15 min 20 - 25 min 15 min
April 2008 From Azoury, 2000
Activity-Based Costing (ABC) in radiotherapy
Type of treatment Cost (EURO)
Palliative irradiation (10 fractions) 1,686
Breast irradiation (25 fractions) 2,701
H&N irradiation (35 fractions) 4,724
April 2008
CT MRI (T2) FDG-PET
PRE-R/
WEEK 3
WEEK 5
(Week 2)
(Week 4)