General Principles and Practical Points in Target Delineation: Esophageal Cancer --- Presented at Spring Annual Meeting of Korean Society of Radiation Oncology (Jeju, Korea)

1. General Principles and Practical Points
in Target Delineation: Esophageal Ca
Yong Chan Ahn, MD, PhD
Dept of Radiation Oncology
Samsung Medical Center
Sungkyunkwan University School of Medicine

2. Anatomy & Basics

3. Histology
Sq cell ca Adenoca
Etiology Tobacco/alcohol Barrett’s esophagus
GERD, smoking,
high body mass
Incidence Decreasing in US Increasing in US
Location Upper to mid
thoracic
GE junction
Prognosis Better prognosis

9. AJCC 7th edition
AJCC 6th AJCC 7th
T1 Subdivided into T1a and T1b
T4 Subdivided into T4a and T4b
N stage – N1 N1~3 based on number of nodes (+)
M1a
M1b
M1a  regional LN
Regional LN Cervical to celiac nodes
Overall stage Incorporation of tumor grade,
location and histology (AD vs SQ)

10. AJCC 6th vs 7th

11. NCCN Guidelines

20. Variability in Target Delineation

22. • Median Jaccard conformity index was 0.69, with
28% (14 of 50 investigators) achieving JCI≥0.7.
• Median geographical miss index was 0.09.
• Mean discordance index was 0.27.
• CI was highest in middle section of volume,
where tumor was bulky and more easily
definable.

23. • GTV delineation by 6 radiation oncologists on
10 patients using CT alone and PET-CT.

24. Inter-personal (6 observers)
Intra-personal

26. • GTV delineation by 3 radiation oncologists on
28 patients using CT alone and PET-CT.

29. • PET-CT modified tumor
delineation in 61% (17/28) in
cranial and/or caudal
direction.
• Mean concordance indexes
for CT- and PET-CT-based
CTV/PTV were 72%/77%,
vs. 72%/76%.
• PET and CT may improve
target volume definition with
less geographic misses, but
without significant effects on
inter-observer variability.

37. • PET was able to identify most primary tumors, with a
sensitivity and specificity for the detection of metastatic
lymph nodes of 30~93% and 79~100%.
• PET-CT resulted in target volume changes.
• Evidence on validity of PET-CT is very limited.
– 3 studies  significant positive correlation between PET-based
tumor lengths and pathological findings.
– 2 studies  inter- and intra-observer variability (results were
not same).
– No study demonstrated improved locoregional control or
survival by PET-CT.

40. LR CC AP
Mean 3.5 8.3 4.0
SD 1.8 3.8 2.6

41. Importance of Target Delineation

43. From Classic to Conformal
• Fundamental tenet of RT is delivery of high dose
to tumor while limiting dose to normal tissues.
• OAR’s and normal tissue tolerance have limited
dose to tumor.
• Conformal RT:
– Dose escalation to tumor while limiting dose to
normal tissues
– Better local control, enhancing quality of life, and
reducing Tx-associated morbidity
– Need to improve accuracy of every step!

44. RT Process
Steps in RT that can be represented by links in a chain.
Tx accuracy will be limited by the weakest link in the chain

45. Can IGRT Be Solution?
If you can’t see it, you can’t hit it.
And if you can’t hit it, you can’t cure it.
(by Harold Johns)
• IGRT:
– The latest imaging techniques to monitor target
volume.
– As good as accuracy only when target is known!
– Improved accuracy by IGRT is limited by target
delineation accuracy.

46. Target delineation: The problem!
• Current practice in RT uses ICRU definition of
target volume
– Gross tumor volume (GTV)
– Clinical target volume (CTV)
– Planning target volume (PTV)

47. GTV
• GTV is part of tumor that is visible with 3D
imaging.
• Actual GTV delineated is dependent on imaging
modality utilized and data acquisition process.
• Uncertain & variable!

48. GTV to CTV
• Margins!
– Based on assumptions from clinical or pathological
experience.
– Subject to high degrees of uncertainty.
– Making target delineation highly imprecise.
• Uncertain & variable!

49. CTV to PTV
• Margins!
– Based on clinical experience
– +/- suggested theoretical margins based on observed
variations.
• PTV frequently includes large amount of normal
healthy tissue within high dose volume 
limiting total dose to PTV.
• Uncertain & variable!

50. Importance of Target Delineation
• Target contouring errors generate systematic errors
which no level of image guidance will eliminate.
• Target delineation accuracy cannot be overemphasized!

51. Guideline (Protocol)
• Lack of continuous education and training --
cause of variability in tumor delineation.
• Guidelines for tumor delineation increases
agreement between observers (prostate, lung, and
nasopharynx):
– Average variation of GTV was reduced from 20% to
13% with protocol.
– Protocol included level and window settings, and
tumor identification by diagnostic radiologist.

52. Collaboration with Diagnosticians
• Development of closer links between radiologists
and oncologists to optimize interpretation of
imaging and target volume definition.
• Radiologists -- to read and interpret films
• Oncologists -- to treat cancer

53. Conclusion
• Tumor delineation:
– Is the weakest link in RT accuracy,
– Will continue to have significant impact,
– Improvement is necessary.
• Possibility of converging and making tumor
identification and definition less subjective and
less observer-dependent with advancement of
computer programming and imaging technology
(MRI, PET).

54. Classic RT Target Volumes
• Large T: bilat SCN + whole mediast + Lt gastric –
’97 Mei
• Middle T: bilat SCN + mediast – ’91 Teniere
• Small T: bilat lower neck + SCN + upper mediast
– ’89 Nishimura
• Tumor bed only – ’93 Fok
• Tumor bed + vertical 5~8 cm + horizontal 2 cm +
no bilat SCN – ’01 Bedard

55. Target Delineation Tips:
Definitive RT Setting
(Japanese Style?)

57. Initial Findings of Primary Tumor
• Circumferential location
• Tumor size
• Tumor type
• Depth of tumor invasion

62. Metastatic Lesions
• Lymph node metastasis:
– Naming, number and extent of LN’s
– LN groups
– Degree of LN (N)
• NX: LN metastasis cannot be assessed
• N0: No lymph node metastasis
• N1: Metastasis to Group 1 LN
• N2: Metastasis to Group 2 LN
• N3: Metastasis to Group 3 LN
• N4: Metastasis to Group 4 LN

73. Target Delineation Tips:
Definitive RT Setting
(Chinese Style?)

74. • Feb 2003~Dec 2008, Shandon Cancer Hospital
• 1,077 thoracic ESCC patients who underwent
surgery

76. • Feb 2003~Sep 2011, Shandon Cancer Hospital
• 1,893 thoracic ESCC patients who underwent
surgery
JTO, ’13

78. Feb/’03~Dec/’08 (N=1,077) Feb/’03~Sep/’11 (N=1,893)

79. • 45 observational studies with a total of 18,415
patients were included in meta-analysis.

82. 2010 (N=1,077) 2013 (N=1,893)

84. Target Delineation Tips:
Salvage RT Setting

85. • July 2005~January 2009, 140 patients with
recurrent or metastatic thoracic esophageal SqCC
were treated with surgery alone.

86. • Surgical LND: 2 filed in 119; 3 field in 21
• Pathologic surgical margins were negative.
• None received CTx or RT before and after surgery.

87. • 350 recurrence or metastasis in 140 patients.
• Median time to progression = 18.3 (15.4~21.1) mo

88. How Do I Do?
(Gangnam Style?)

89. Case: M/58 Cervical~Upper Thoracic
• Squamous cell ca, cT3N1

90. Case: M/58 Cervical~Upper Thoracic
• Definitive RT (66~70 Gy/6.5~7
weeks) concurrent with FP chemo #2

91. Case: M/60 Low Thoracic
• Squamous cell ca, cT3N2

92. Case: M/60 Low Thoracic
• Preop RT (44 Gy/4.5 weeks)
concurrent with FP chemo #2

93. Case: M/70 Local Recurrence
• 2Y 3M ago: s/p I-L Op, pT2N0
• A-site recurrence, rT4N1

94. Case: M/70 Local Recurrence
• Salvage RT (66~70 Gy/6.5~7 weeks)
concurrent with FP chemo #2

95. # of Esophageal Ca Pt at SMC
(~Nov 2012)
4
14
27
14
27
43
28
54
40
50
64
47
36
55
60
92
67
83
97
0
20
40
60
80
100
120
Total 902 pts

96. Aim of RT
Total 902 pts

97. Overall Survival vs RT Setting

98. Whenever Possible!
• Gather any small piece of important information:
– Clinical – P/E, EGD, EUS, CT, PET…
• Evaluate operability & resectability (anatomic &
physiologic staging).
• Consider aggressive & multi-modal approach.
• Optimize RT target volume to achieve Tx goal.
• Monitor and adapt to changes during RT course.

99. Whenever Possible!
• To go, or not to go?
– 길이 아니면 가지 말라.
– 질 것이 뻔한 싸움은 덤비지 말라.
• Stay optimistic & affirmative if not definitely negative!
– Down-staging if equivocal.
– 보이는 gross tumor를 control 못하면서, 안 보이는
subclinical metastasis를 너무 걱정할 필요가 없다.
• If I have to go, go well!
– 최악의 부작용은 local failure!
– Acute & reversible side effect는 차라리 즐겨라.
– Life-long complication은 무조건 피하도록.

100. Whenever Possible!
• 어떤 경우에도 환자는 길고, 고통스러우며, 비
싼 방사선치료를 받고자 하지 않는다.
• In every case,
– As effective as possible.
– As less toxic as possible.
– As simple as possible.
– As short as possible.
– As economic as possible.