1. IMRT planning for HN cancr:
Some clinical issues
Avraham Eisbruch
University of Michigan

2. Defining the targets
The GTV:
1. Clinical information: palpation,
mirror/fiberoptic exam, direct endoscopy report
2. Imaging: Planning CT (contrast-enhanced)
• Register with MRI / PET

3. Nasopharynx ca
CT

4. Nasopharynx ca
MRI

5. Using FDG-PET to define the GTV
• How exactly should PET be used?
• If the PET-based and CT-based GTVs
differ, what is the “truth”?

6. Using PET-CT for GTV delineation
CT-GTVs
The GTVs on CT and FDG-PET usually correlate well

7. FDG-PET may define the GTV better than CT
Lt BOT cancer. The GTV is blurred by CT artifact

8. FDG-PET may define the GTV better than CT
Lt tonsil cancer. CT: Retropharyngeal node was part of the CTV.
PET: it should be a GTV.

9. FDG-PET may be false negative: failure to detect
obvious gross disease
Primary ca #1 Primary ca
#1
#2
LN #2: extensive necrosis; not detected by PET

10. PET may be false positive: Benign lymphatic tissue in the
BOT accumulates FDG
Consult Nuc Med to verify that the signal intensity/SUV are right

11. Suspicious nodes on CT, PET (-): CTVs or GTVs?
? + +
?
Use clinical judgement

12. PET vs. other imaging modalities
vs. LN pathology
Adams et al, Eur J Nuc Med 1998

13. Larynx cancer: Matching the surgical specimen, CT, and PET
Daisne, …Gregoire, Radiology 2004

14. Matching the surgical specimen, CT,
MRI, and PET
• The GTVs according to PET were usually
slightly smaller than the CT/MRI volumes
• No modality showed the extent of the
primary with complete accuracy
– evaluation of submucosal tumor extension was
deficient by all modalities.
Daisne, …Gregoire, Radiology 2004

15. Summary: Outlining the primary
tumor GTV
• Use the PET and CT/MRI information for
composite GTV delineation
• Add clinical examination results, especially
for the mucosal extent of the gross disease

16. Summary: Outlining the nodal GTVs
• Wherever a node is PET (+), include in the
GTV
• If CT is highly suspicious and PET is (-),
include in the GTV.
• In borderline cases of (+) CT and (-) PET,
use clinical judgement to define as GTV or
CTV.

17. Can FDG-PET be used to define the
CTVs?
• Sentinel node biopsy and neck dissection in the
clinically (-) neck: nodes were examined by the
pathologists at 2 mm slices
• Occult metastases (size 1.2-1.5 mm): in 5/12
patients;
• FDG PET correctly identified only one (sensitivity
of 25%).
• We cannot rely on PET for outlying the CTV.
Stoeckli et al, Head Neck 2002

18. Outlining Lymph Node CTVs
• Which LN groups at at risk for each tumor
site and stage?
• How should the LN be delineated on the
planning CT?

19. Neck Node
Levels
Som et al.,
Arch.
Otolaryngol.
Head Neck
Surg.1999

20. Gregoire,
Levendag,
et al.
WWW.RTOG.ORG
Researchers
HN Atlas
www.rtog.org/hnatlas/main.htm

21. Cranial-most extent of neck CTV
• In the clinically (-) non-nasopharyngeal ca:
– The bottom of the transverse process of C1
• Gregoire et al
This will ensure coverage of the JD (sub-
digastric) nodes

22. Oral cavity lymphatics
Rouviere, 1938

23. Pharyngeal lymphatics
Rouviere, 1938

24. What about nasopharyngeal cancer?
Lateral retroph. n
Junctional n.

25. Nasopharynx ca
Level II
Level V

26. Should we biopsy
all non-specific
parotid nodules?
IJROBP 2007

27. Parotidean LN metastases in NPC

28. Eustachian Tube: Lymphatic Drainage
In addition to sub-digastric and RPN: Lymphatics to parotidean nodes
H. Rouviere, 1932

29. Parotidean LN metastases in NPC
Due to retrograde flow when level II is heavily involved?

30. Tonsil ca, T3N2c
Primary Tu
Parotidean LN met

31. No nasopharyngeal involvement…

32. …but significant ipsilateral level II nodal involvement

33. Parotidean metastases
• Risk of retrograde lymphatic drainage when
level II is heavily involved
• Suggest: omit ipsilateral parotid sparing if
ipsilateral level II is heavily involved.

34. Can we improve outcome by GTV
dose escalation?
• Escalate doses to the whole GTV
• Escalate the doses to the parts of the GTV
judged to be at highest risk

35. Escalate/accelerate doses to the
whole GTV
• Baylor: “SMART”: 60 Gy/2.4 Gy/fraction
– BED2Gy 70 Gy, over 5 weeks
– Concurrent with chemotherapy: not tolerable
due to acute mucositis
• Amosson, ASTRO 2003

36. Escalate/accelerate doses to the
whole GTV
• Nasopharynx ca: 64.8/2.4/fr. Over 5.5 weeks conc.
with cisplatin
– “modest increase in toxicities”
• WS Koom, Head Neck 2008
• Larynx/hypopharynx ca: 67.2 Gy/2.4 conc. with
cisplatin
– “acceptable acute toxicity”.
• Guerrero-Urbano , Radiother Oncol 2007

37. High fraction doses: Oropharyngeal ca
• RTOG 00-22: 66 Gy/30 fractions, no chemo
– Few long-term complications
• 6% ORN
• Eisbruch et al, IJROBP 2009
• Stanford: 66 Gy/30 fractions, conc. chemo
– Few long-term complications
• Orocutaneous fistula, tracheal stenosis, ORN
• Daly ME et al, IJROBP 2009

38. Moderately high fraction doses:
laryngeal/hypopharyngeal ca
• MSKCC: 70 Gy/32-33 fractions (2.12 Gy/fraction) conc
with chemo
– Late complications:
• 20% PEG dependency at 2 years
• Laryngeal necrosis, necrotizing skin fascitis
• Lee NY, IJROBP 2007

39. Escalate the dose to part of the GTV
• The FDG-PET avid part of the GTV tumor
• Hypoxic regions within the GTV

40. CTV
• Outlining the CTV
– Anatomically: taking into account the
compartments at risk
– Uniformly, arbitrary margins: 1-2.5 cm

41. CTV Doses and their BED(2 Gy)
(assuming alpha/beta 10 Gy and loss of 0.7 Gy/day of
extending treatment)
Total dose (Gy) Dose /fraction (Gy) BED2 (Gy)
63 1.8 60
59 1.7 54
56 1.6 49
52 1.5 42

42. Considerations
• Conc chemo:
– Adds 12 Gy/ 2 Gy fractions (Kasibhatla et al,
IJROBP 2007)
– Adds 7 Gy/2 (Fowler JF, IJROBP
• Very good prognosis patients, such as HPV-
related oropharyngeal ca, may require quite
low doses

43. How should we treat the low
neck?

44. NTCP: Glottic edema grade 2+
Extensive neck RT for non-laryngeal cancer, mostly no conc. chemo
Rancati T, IJROBP 2009

45. No effort to spare the larynx/esophagus: High rates of dysphagia
after whole-neck IMRT compared with split-field.
Fua et al, 2007

46. split field vs whole neck IMRT
Head Neck 2004

47. Amdur et al, Head Neck 2004

48. Laryngeal shield: do not extend caudally
because jugular vein and nodes become more medial
Mendenhall, Amdur, Million, 1992

49. Extend the midline block
to shield also inferior constrictor and esophagus
Caudell JJ IJROBP 2009

50. Whole neck IMRT
or
upper neck IMRT + abutted AP low neck field
• Abutting AP low neck field: 30% of the
recurrences were in the low neck
– Chao et al IJROBP 2003

51. Whole-neck IMRT in cases of low neck involvement or high risk

52. Higher weight to targets or organs
• PTV doses: 99%-107% presc. doses
• Larynx/constr./esophagus: reduce mean
dose as much as possible (<20 Gy)
– Targets weigh higer than organs
– Organs weigh higher than targets

53. PTVs (yellow/purple) weigh lower than larynx/inf. constrictor

54. PTVs (yellow) weigh higher than esophagus

55. The low neck
• Split-field technique is simpler, faster, less
monitor units, likely less skin toxicity
• Whole-field IMRT allows better certainty in
target coverage
– may be preferable in cases of gross low neck
involvement or when the low neck is at high
risk

56. Rosenthal et al, IJROBP 2008

57. Rosenthal et al, IJROBP 2008

58. Oral cavity
Not included in the cost function

59. Oral cavity
Included

60. Lt tonsillar cancer

61. After 23 fractions (GTV dose 46 Gy)
concurrent with carboplatin+taxol
Estimated lip mucositis site dose 30 Gy/1.3 Gy/fraction

62. Mucosal point doses vs. length of time of mucositis
Narayan et al, IJROBP 2008;72:756

63. Lt tonsillar ca, chemo-RT: oral cavity outside the PTVs spared

64. Induction chemotherapy for HN cancer
Response to induction chemo:
CR 17%, PR 55% CR 9%, PR 59%
Patients proceed to chemo-RT after most tumors shrink by induction.
GTVs: the pre-chemo or the post-chemo volumes?

65. Neoadjuvant chemo: Its tumor effect may be trivial even if
clinical CR is achieved.
Ian Tannock

66. After induction chemotherapy
• Use the pre-chemo targets
• It is essential to examine the patient, have
adequate imaging studies, and preferably simulate
the patient before chemo starts.
• Re-simulate after induction chemo and register the
pre-chemo GTVs to the new planning CT.
• Same principle: do not reduce the GTV as tumor
shrinks during RT.
Salama et al, IJROBP 2009

67. Acknowledgements
• UM Rad-Onc residents, • Speech pathology
students & fellows – Teresa Lyden
– Felix Feng – Marc Haxer
– Mary Feng • Dentistry
– Alex Lin – Carol-Anne Murdoch-Kinch
– Siavash Jabbari – Jonathan Ship
– Laura Dawson • Rad-Onc Physics
– Aron Popovtzer – Randall Ten Haken
– Iris Gluck – Karen Vineberg
• Otolaryngol-HN Surgery – Dick Fraas
– Doug Chepeha • NKI, Amsterdam
– Ted Teknos – Marco Schwartz
– Carol Bradford – Coen Rasch
– Gregory Wolf
Supported by NCI grants PO1 59827 and HN SPORE P50 CA/DE97248