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

Anatomy & Basics

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

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)

AJCC 6th vs 7th

NCCN Guidelines

Variability in Target Delineation

• 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.

• GTV delineation by 6 radiation oncologists on

10 patients using CT alone and PET-CT.

Inter-personal (6 observers)

Intra-personal

• GTV delineation by 3 radiation oncologists on

28 patients using CT alone and PET-CT.

• 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.

• 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.

LR CC AP

Mean 3.5 8.3 4.0

SD 1.8 3.8 2.6

Importance of Target Delineation

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!

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

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.

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)

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!

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!

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!

Importance of Target Delineation

• Target contouring errors generate systematic errors

which no level of image guidance will eliminate.

• Target delineation accuracy cannot be overemphasized!

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.

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

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).

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

Target Delineation Tips:

Definitive RT Setting

(Japanese Style?)

Initial Findings of Primary Tumor

• Circumferential location

• Tumor size

• Tumor type

• Depth of tumor invasion

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

Target Delineation Tips:

Definitive RT Setting

(Chinese Style?)

• Feb 2003~Dec 2008, Shandon Cancer Hospital

• 1,077 thoracic ESCC patients who underwent

surgery

• Feb 2003~Sep 2011, Shandon Cancer Hospital

• 1,893 thoracic ESCC patients who underwent

surgery

JTO, ’13

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

• 45 observational studies with a total of 18,415

patients were included in meta-analysis.

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

Target Delineation Tips:

Salvage RT Setting

• July 2005~January 2009, 140 patients with

recurrent or metastatic thoracic esophageal SqCC

were treated with surgery alone.

• Surgical LND: 2 filed in 119; 3 field in 21

• Pathologic surgical margins were negative.

• None received CTx or RT before and after surgery.

• 350 recurrence or metastasis in 140 patients.

• Median time to progression = 18.3 (15.4~21.1) mo

How Do I Do?

(Gangnam Style?)

Case: M/58 Cervical~Upper Thoracic

• Squamous cell ca, cT3N1

Case: M/58 Cervical~Upper Thoracic

• Definitive RT (66~70 Gy/6.5~7

weeks) concurrent with FP chemo #2

Case: M/60 Low Thoracic

• Squamous cell ca, cT3N2

Case: M/60 Low Thoracic

• Preop RT (44 Gy/4.5 weeks)

concurrent with FP chemo #2

Case: M/70 Local Recurrence

• 2Y 3M ago: s/p I-L Op, pT2N0

• A-site recurrence, rT4N1

Case: M/70 Local Recurrence

• Salvage RT (66~70 Gy/6.5~7 weeks)

concurrent with FP chemo #2

# 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

Aim of RT Total 902 pts

Overall Survival vs RT Setting

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.

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.

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.