Esophageal cancer practical target delineation 2013 may
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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
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Anatomy & Basics
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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
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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)
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AJCC 6th vs 7th
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NCCN Guidelines
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Variability in Target Delineation
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• 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.
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• GTV delineation by 6 radiation oncologists on
10 patients using CT alone and PET-CT.
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Inter-personal (6 observers)
Intra-personal
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• GTV delineation by 3 radiation oncologists on
28 patients using CT alone and PET-CT.
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• 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.
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• 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.
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LR CC AP
Mean 3.5 8.3 4.0
SD 1.8 3.8 2.6
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Importance of Target Delineation
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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!
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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
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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.
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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)
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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!
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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!
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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!
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Importance of Target Delineation
• Target contouring errors generate systematic errors
which no level of image guidance will eliminate.
• Target delineation accuracy cannot be overemphasized!
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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.
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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
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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).
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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
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Target Delineation Tips:
Definitive RT Setting
(Japanese Style?)
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Initial Findings of Primary Tumor
• Circumferential location
• Tumor size
• Tumor type
• Depth of tumor invasion
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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
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Target Delineation Tips:
Definitive RT Setting
(Chinese Style?)
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• Feb 2003~Dec 2008, Shandon Cancer Hospital
• 1,077 thoracic ESCC patients who underwent
surgery
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• Feb 2003~Sep 2011, Shandon Cancer Hospital
• 1,893 thoracic ESCC patients who underwent
surgery
JTO, ’13
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Feb/’03~Dec/’08 (N=1,077) Feb/’03~Sep/’11 (N=1,893)
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• 45 observational studies with a total of 18,415
patients were included in meta-analysis.
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2010 (N=1,077) 2013 (N=1,893)
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Target Delineation Tips:
Salvage RT Setting
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• July 2005~January 2009, 140 patients with
recurrent or metastatic thoracic esophageal SqCC
were treated with surgery alone.
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• Surgical LND: 2 filed in 119; 3 field in 21
• Pathologic surgical margins were negative.
• None received CTx or RT before and after surgery.
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• 350 recurrence or metastasis in 140 patients.
• Median time to progression = 18.3 (15.4~21.1) mo
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How Do I Do?
(Gangnam Style?)
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Case: M/58 Cervical~Upper Thoracic
• Squamous cell ca, cT3N1
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Case: M/58 Cervical~Upper Thoracic
• Definitive RT (66~70 Gy/6.5~7
weeks) concurrent with FP chemo #2
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Case: M/60 Low Thoracic
• Squamous cell ca, cT3N2
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Case: M/60 Low Thoracic
• Preop RT (44 Gy/4.5 weeks)
concurrent with FP chemo #2
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Case: M/70 Local Recurrence
• 2Y 3M ago: s/p I-L Op, pT2N0
• A-site recurrence, rT4N1
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Case: M/70 Local Recurrence
• Salvage RT (66~70 Gy/6.5~7 weeks)
concurrent with FP chemo #2
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# 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
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Aim of RT Total 902 pts
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Overall Survival vs RT Setting
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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.
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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.
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Whenever Possible!
• 어떤 경우에도 환자는 길고, 고통스러우며, 비싼 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.
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