1) The document discusses optimal practice in radiation treatment for head and neck cancer in the 21st century, focusing on balancing treatment targets and sparing normal tissues using available technology and expertise. 2) It reviews treatment options and approaches for different stages of head and neck cancer, highlighting evidence that altered fractionation and chemoradiation can improve outcomes over standard radiation alone. 3) Challenges of implementing intensity-modulated radiation therapy (IMRT) for head and neck cancer are discussed, as well as examples of how IMRT can improve target coverage and tissue sparing compared to conventional techniques.

1. How would we practice today using optimal human
resources, technology and techniques ?
“Achieving the Achievable”
HEAD AND NECK CANCER
Radiation Treatment Program Symposium
“The Future of Radiation Treatment in the 21st Century”
2 – 3 March, Toronto
Brian O’Sullivan MD, FRCPC
Department of Radiation Oncology
University of Toronto

2. Overview / Objectives
• What is optimal practice and how do we deliver it in the
present human and technology resource environment ?
• Is their a rationale for using approaches requiring more
expertise and intensive resources ?
• How difficult is it to implement comprehensive IMRT for
head and neck ?
• Some problems in delivering very precise treatment
techniques
• Some non-traditional examples of the use of precision
radiotherapy techniques (eg IMRT)
• Additional barriers to practice today that conflict with
available options

3. Treatment Options in HN SCC
Early stage disease (T1 and small T2)
– Single modality treatment (RT vs surgery)
– Usually conservative RT regimens 50/20 f – 66/33 f
Intermediate stage disease (large T2; small T3 ‘exophytic’;
N1 some N2s)
– Most usual: Radiotherapy +/- chemotherapy or Cetuximab
– RT alone is intensified altered fractionation
– If surgery performed the majority also need post-op RT (margins,
# nodes, ECE)
Advanced stage disease (large T3; T4; Some N2s and N3)
– Most usual: concurrent Chemo-Radiotherapy or RT-Cetuximab
– May use composite primary surgery with neck dissection. And
post-op RT (margins, # nodes, ECE) and often Chemo (margins
and ECE)
– Functional and cosmetic deficits should be considered

4. Approaches to locally advanced
Head and Neck Cancer
• MARCH: Meta-Analysis of Radiotherapy in
Carcinomas of Head & Neck (n= 6,515 patients)
Altered fractionation radiotherapy (RT) improved
survival as compared to standard RT: Absolute benefit
3·4%
8% using Hyperfractionated RT with augmented dose
Bourhis et al Lancet 2006
• MACH-NC: Meta-Analysis of Chemotherapy in Head
& Neck Cancer (n=17,858)
Chemotherapy (CT) added to RT, improved survival
by 5%
8% using concurrent chemo-RT
Bourhis et al ASCO 2004

5. Post-operative Adjuvant Treatment
of head and neck Cancer
Postop Radiation +/- Cisplatinum Postop Radiation +/- Cisplatinum
NEJM 2004 Head and Neck 2005

6. Examples of Schedules with or without chemotherapy
Challenge Multi-phased Single Phase IMRT
is the (2Gy / fraction) (variable target fractions)
Radiobiology 7 wk course 7 wk course 6 wk course
PTV1 50 Gy in 25 f 56 Gy in 35 f 54 Gy in 30 f
‘Microscopic’ (Cord shield 40 Gy) (No cord shield)
PTV2 70 Gy in 35 f 70 Gy in 35 f 66 Gy in 30 f
‘Gross’
PTV3 60 Gy in 30 f 63 Gy in 35 f 60 Gy in 30f
<2 cm node **
*Requires cord shielding, electrons, low neck matching (3 or 4 ‘phases’)
**Intermediate dose (PTV3) especially useful for small nodes at the level
of the brachial plexus, or for dubious small nodes in the radiology report

7. What is optimal ?
• Potential to include the Target Objects properly
• Spare as much normal tissue as possible, and especially
normal tissues where function is compromised
– Critical neurological tissues
– Salivary function
– Swallowing mechanism
– Mandible
• Options for augmentation (combined modality) are
numerous (available skills and resources affect choice)
• Several balances in decision-making re: technique
– Balance against resources to accomplish
– What drives the decision ?
• Inclusion of the target
• Avoidance of normal tissues
• Accomplish both: “Include and avoid”

8. Prescribed Median Minimum % Intended
Dose (Gy) Dose to GTV Dose
Phase I 40 38.4 96%
Phase II 10 7.3 73%
(cord and brain
stem shield)
Phase III 10 6.5 65%
(chiasm shield)
Phase IV 6 4.0 67%
(High Energy
GTV with dose template boost)
(outlined using archived MRI
restored from DAT )

9. Dose coverage issues:
T4 disease with
bulk and normal • Surprisingly good outcome historically
with RT alone and 2D planning despite
tissue inadequate coverage - about 70-75%
constraints control in major centres
• Landmark Intergroup 0099 Chemo-RT
had very poor control in the control arm
• May have shown us that concurrent
chemotherapy can compensate for
inadequate coverage in multicentre setting
• Also potentially cure could be higher if
local control more optimal; alternatively
some of the effect of chemo may
disappear

10. IMRT in NPC
• Many of these patients
were treated with
concurrent
chemotherapy
• Need new approaches
to improve systemic
outcome

11. 25% recovery of IMRT significantly
pre-RT stimulated better than CRT
parotid flow in terms of
parotid sparing,
and improved
QOL (SF36,
EORTC)

12. • 70-Gy isodose
confomed around the
PTV for the gross tumor
and 59.4 Gy to the
ipsilateral neck
• 54 Gy to contralateral
neck PTV
• Simultaneously

13. Lee at al 2006

14. 3-yr actuarial CBRT IMRT P-value
Local progression free 85% 95% 0.17
Regional PF 95% 94% 0.90
Locoregional PF 82% 92% 0.18
Distant–free 85% 86% 0.78
Disease-free 76% 82% 0.57
Overall survival 81% 91% 0.10
Treatment-related death 3 0
Tube dependent (2yr) 21% 4% 0.02
Lee at al 2006

15. Technical delivery
Tissue sparing
potential of IMRT
Conventional conformal
plan in 2/3 phases
Improved target coverage
in numerous sites

16. • Without mucosal dose objective
IMRT will treat a larger amount of
mucosa with clinically relevant doses
compared to conventional RT
• With dose objectives, the reverse is true
up to 30% reduction in the mucosal
volume in the high-dose region
compared with conventional RT (p <
0.01).

17. Caveats about IMRT for Head and Neck Cancer
Preliminary Results:
Extraneous and unusual/unexpected dose deposition:
“Nausea, Vomiting, and Other Unanticipated Toxicities During
IMRT for Head and Neck Squamous Cell Carcinoma”
• Headache
• Nausea and vomiting
• Hair
• Eyes and lacrimal glands
• Lips
• Larynx
• Skin
• Mucosa
JW Fan, DI Rosenthal et al 2007: ASTRO / ASCO / AHNS Palm Spring

18. “Labored swallowing, prolonged eating times, and the limited
range of foods that can be swallowed lead to disruption
of relationships and social isolation.”

19. 50 Gy
Pretreatment 3 months post XRT/chemo 50 Gy
Eisbruch et al IJROBP 60(5) 1425,2004
Standard IMRT Sparing IMRT

20. N = 142
• Saliva flow rates +/-
stimulation
• 18 months after radiation
therapy
• mean doses of 0, 20, 30,
and 40 Gy, respectively.
Conclusions:
• Saliva production is affected
significantly by radiation,
• but with doses <25–30 Gy,
recovery is substantial and
returns to pretreatment
levels 2 years after RT.

21. 3 Eras of IMRT Provision at PMH
(Full inverse planning)
Hesitation
Implementation 600 / yr
Accomplisment
300
250
Number of patients
200
150
100
50
0
Jan-01 Jan-02 Jan-03 Jan-04 Jan-05 Jan-06

22. Building an IMRT Factory, Courtesy of Stephen Breen
• ICRU 62
• Descriptive • General
•R2CTV56 • Documented
• Retrospective • Adapted by
audit planners
Experience-driven
•Contours (all)
•Plan (Physics)
Product: •Daily Imaging
High-volume •(RT unit)
Head & Neck IMRT
Programme

23. Quality Assurance Steps
Volumes Appropriate
CT Sim
Nomenclature Consistent
Contours
Protocols
Planning
Coverage Doses Patient
acceptable Positioning
Delivery Acceptable
(measurement or
Treatment
secondary calculation)

24. This H&N structure nomenclature, contouring
guidelines and terminology system was
implemented to:
• facilitate multidisciplinary communication
between radiation oncologists, planners and
physicists
• facilitate quality assurance review of H&N
planning
• enable the automation of complex programming
tasks within our planning system
• facilitate audit of outcomes
Slide: courtesy John Kim

25. The Primary – the Radiation Oncologist’s Role is to
Contour the Gross Objects and the Putative microscopic
risk area and label appropriartely
GTV CTV70 CTV56
Corresponding PTVs PTV70 PTV56
(Planners role)
T4a N2c M0 Tongue Base Cancer
Slide: courtesy John Kim

26. The Neck
Right neck shown only
Rretro RretroCTV70
RCTV56
R2A3 R2A3CTV70
Corresponding PTVs RretroPTV70 RPTV56
R2A3PTV70
T4a N2c M0 Tongue Base Cancer
Slide: courtesy John Kim

27. Daily Online Setup Correction

28. Cone-beam CT Images of the
Head & Neck
Cone-beam CT datasets fully 3D.
Permit arbitrary reformatting for interpretation.
Well-suited to image-guidance applications.
Exquisite anatomical detail possible

29. Random Uncertainty: weekly cone
beam studies

30. NCI – All Ireland - Nov 2006
Daily Cone beam images
can:
1. TrackCT sim
Planning response Day 1 Day 7
2. Determine dose
received
3. Guide adaptation
4. Determine PTVs
Data from David Hwang
Similar data on spinal cord
Mehrdad Vakilha
Day 14 Day 21 Day 35

31. Evaluation of a Semi-Automated Segmentation
Method for Delineation of Organs at Risk and
Lymph Node Target Volumes in Head and Neck
Radiotherapy Planning
Michael Kaus
Philips Radiation Oncology Systems, Madison, WI
J. Kim, B. O'Sullivan, A. Mansouri, S. Breen, L. A. Dawson, D. A. Jaffray
Radiation Medicine Program, Princess Margaret Hospital, University Health Network
University of Toronto, Toronto, ON, Canada
ASTRO 2006

32. The potential clinical
benefits
A population-based semi-automated
segmentation
– assist physician contouring of complex
H&N cases
– improve efficiency of contouring tasks
– facilitate implementation of image-
guided and adaptive RT

33. Is treating T1 Larynx with IMRT reasonable ?
• Ultrasonography used to measure difference (R vs L) in carotid wall
thickness (intima-media thickness) in 42 unilaterally irradiated
parotid cancer patients.
• 5 had a vascular ischaemic event (3 TIA, 2 infarction) at a median of
11 years (range 5.9–13.1 years) following RT.
• In 4 of these 5, it occurred in the area of the irradiated carotid artery.
The mean difference in IMT was 1.1 mm.
• One patient developed cerebral infarction contra-lateral to the side
of RT and showed no difference in IMT (0 mm).

34. Is treating T1 Larynx with IMRT reasonable ?
50 Gy 50 Gy
Traditional Volume (IMRT planned) Optimal Volume (IMRT planned)
• Where the target is not compromised
• Where normal tissues can be spared
• Why not place the dose where you want it ?
• Potential gains: carotid protection; arytenoid protection

35. Is treating BCC with IMRT reasonable ?
• Where the target is not compromised
• Where normal tissues can be spared
• Why not place the dose where you
want it ?
• Potential gains: Eye preservation

36. Is treating BCC with IMRT
reasonable ?
Patient is ANED at 5
years. Has a small
cataract

37. The Role of PET:
• Staging / assessment • 8 wks post
• Prediction (probably chemo-RT
need more than FDG)
• Determination of • Anatomic
Response imaging
negative
• Neck
Pre-chemo RT dissection
positive in
4 nodes
• ANED 3
years later

38. Observer variability CT, CECT, PETCET
• Do observers draw the same volumes on
CT and CT-PET?
– 8 observers (6 RO, 2 NR)
– 10 H&N patients
– GTVs on CECT, CT-PET, CT CECT PETCT
– Involved nodes
Findings:
• Specialty makes no difference
• We cannot confirm the perception that
FDG-PET reduces uncertainty in primary
tumor target volume delineation
• Differences are small, overwhelmed by
inter-observer differences
• Lymph node delineation may be
facilitated
• Suspicion – PET aids concurrence
De Silva S et al ASTRO 2005 and 2006

39. A Phase III Study of Radiotherapy ± Cetuximab
(C225) in Patients with Locally Advanced HNSCC
Local-Regional Control Survival
Probability
Probability
RT + C RT + C
RT RT+C RT RT+C
Patients 213 211 Patients 213 211
Events 105 90 RT Events 117 93
Median 19 m 36 m Median 28 m 54 m RT
1-Year 59% 69% 2-Year 55% 62%
2-Year 48% 56% 3-Year 44% 57%
Log rank p 0.02 Log rank p 0.02
Months Months
RT RT-E
Any Gd 3-4 Any Gd 3-4 Subgroup analyses (HR):
• 26% rc’d once-daily fractionation = 1.01
Skin 91 18 97 34
Mucositis 93 52 91 54 • 18% twice-daily fractionation = 0.74
Dysphagia 63 30 64 25 • 56% concomitant boost radiotherapy = 0.64.
Bonner et al NEJM 2006

41. How should we practice ?
• Use Level 1 evidence based ev
evidence for dose fractionation regimen
• Concerning Technique
– Do not compromise on the targets
– Spare the normal tissues when this is possible
• Place the dose where you want it and where
it needs to go
• Often that means IMRT in complex Head and
Neck cancers

42. Planning & Treatment Team
• Radiation Oncology
– A. Bayley, B. Cummings, L Dawson, J. Kim, B. O’Sullivan, J. Ringash,
J. Waldron
• Physicists
– S. Breen, J. Borg, A. Damyanovich, B. Zhang
• Team 1 Planners
– J.Roussos, M.Ryan, D.Sajac, I Kaminsky, S.Pillay, S.Pizzale,
C.Rocca, L.Chau, P. Rakaric, S.Singh, M.Glinnyi, J.Giovinazzo
• Therapists (33)
– S.Singh, S. Pizzale, I.Kaminsky, C. Rocca, L.Chau, P. Rakaric
C.Bradley, E.Borodina, C.Cerase, C.Chow, C.Dupuis, M.Engel,
C.Field, A.Fung, J.Giovinazzo, M.Glinnyi, B.Guibord,, S.Hua,
S.Huang, J.Loudon, L.Johnson, K.Man, D.Marshall, , E.Mettrick,
G.Parlan, S.Pillay, F.Sie , W.So, A.Sperdutti, M.Tamerou,
W.Tang, V.Truong, G.Wu

43. Additional Key Team Members
Medical Imaging Head and Neck Surgery Image Management Translational Science
Pat Gullane David Jaffray Fei-Fei Liu
Ann Keller
Ralph Gilbert Michael Sharpe Carlo Bastianutto
Eugene Yu Angelo Hui
Jon Irish Jeff Siewerdsen
Dale Brown Bern Norrlinger Sizanne Kame-Reid
RMP IT Infrastructure Ting Jun Zhang
Ian Witterick
Doug Moseley Pathology
Jerry Freeman
Terry Michaelson Anna Kirilova
Peter Neligan Bayardo Perez-
Stuart Rose Kristy Brock
and team Ordonez
Medical Oncology
Lillian Siu
Nursing, Nutrition, Psycho-social
Eric Chen
The Susan Grange Family
Bartley-Smith/Wharton Fund of the PMH Foundation
CARO/ACURA Fellowship Program
Elekta Oncology Systems
Varian Medical Systems