Cancer of the Esophagus

Radiationwww.aboutcancer.com

T1bN+ or

T2-T4a

PreOp

Chemoradiation

then Surgery

Chemoradiation

Most locally

advanced

esophagus cancers

Preoperative Chemoradiotherapy for Esophageal or

Junctional Cancer

P. van Hagen for the CROSS Group

N Engl J Med 2012; 366:2074-2084

randomly assigned patients with resectable tumors to

receive surgery alone or weekly administration of

carboplatin and paclitaxel for 5 weeks and concurrent

radiotherapy (41.4 Gy), followed by surgery.

Results Chem/Rad/Surg Surgery Alone

R0 Resection 92% 69%

Path CR 19%

Hospital Mortality 4% 4%

Median Survival 49.4 mos 24.0 mos

Survival/5y 47% 34%

Months

CRT + Surgery

Surgery

Survival

Arm A: chemotherapy and surgery:

median survival time 21.1 months,

3-year survival rate 27.7%.

Arm B: chemotherapy + radiotherapy

and surgery):

median survival time 33.1 months,

3-year survival rate 47.7%.

JCO February 20, 2009 vol. 27 no. 6 851-856

Comparison of Preoperative Chemotherapy

Compared With Preoperative

Chemoradiotherapy

Arm A chemotherapy and surgery

Arm B chemo + radiotherapy and

surgery):

JCO February 20, 2009vol. 27 no. 6 851-856

Comparison of Preoperative Chemotherapy Compared

With Preoperative Chemoradiotherapy

T1bN+ or

T2-T4a

PreOp

Chemoradiation

then Surgery

Chemoradiation

Most locally

advanced

esophagus cancers

Can you skip the surgery?

Chemoradiotherapy of locally advanced esophageal

cancer: long-term follow-up of a prospective

randomized trial (RTOG 85-01).

JAMA.1999 May 5;281(17):1623

Squamous cell or adenocarcinoma of the esophagus,

T1-3 N0-1 M0. Combined modality therapy: 50 Gy plus

cisplatin and fluorouracil, compared with RT only : 64 Gy

in 32 fractions over 6.4 weeks.

Results Chemo-Radiation Radiation

Survival/5Y 14 – 26% 0%

RTOG 94-05J Clin Onc 2002;20:1167

5-FU + cisplatin + radiation (64.8Gy or

50. 4Gy)

Results High Dose Low Dose

Median survival 13.0 mos 18.1 mos

Surv/2y 31% 40%

Local Failure 56% 52%

Survival from 94-05

50.4Gy

64.8Gy

Months

Randomized Trial of Two Nonoperative Regimens of

Induction Chemotherapy Followed by

Chemoradiation in Patients With Localized

Carcinoma of the Esophagus: RTOG 0113

assigned to receive either induction with fluorouracil,

cisplatin, and paclitaxel and then fluorouracil plus

paclitaxel with 50.4 Gy of radiation (arm A) or induction

with paclitaxel plus cisplatin and then the same

chemotherapy with 50.4 Gy of radiation (arm B)

The median survival time was 28.7 months for patients

in arm A and 14.9 months for patients in arm B (18.8

months for patients in RTOG 9405). The 2-year survival

rate was 56% for arm A and 37% for arm B.

ChemoRadiation Alone,

RTOG

Months

Survival

RTOG 0113

RTOG 9405

JCO 2008;28:4551

Survival with ChemoRadiation

versus Esophagectomy

Chan. IJROBP ;1999:45:265

10y Survival Chemoradiation

with or without Surgery

2 4 6 8 10

Years

No Surgery

Surgery

Bidoli. Cancer 2002:94:352

Chemoradiation with and without surgery in patients

with locally advanced squamous cell carcinoma of

the esophagus.

Stahl. J Clin Oncol. 2005 Apr 1;23(10):2310-7

locally advanced squamous cell carcinoma (SCC) of the

esophagus were randomly allocated to either

Induction chemotherapy followed by chemoradiotherapy

(40 Gy) followed by surgery (arm A),

or the same induction chemotherapy followed by

chemoradiotherapy (at least 65 Gy) without surgery (arm

B).

Overall survival to be equivalent between the two

treatment groups

Local progression-free survival was better in the surgery

group

2-year progression-free survival

Surgery Group 64.3%

Chemoradiotherapy 40.7%

Treatment-related mortality was significantly increased

in the surgery group than in the chemoradiotherapy

group

Treatment Mortality

Surgery 12.8%

ChemoRad 3.5%

Years

Survival

Surgery

Radiation

J Clin Oncol. 2005 Apr 1;23(10):2310-7

Chemoradiation followed by surgery compared with

chemoradiation alone in squamous cancer of the esophagus:

FFCD 9102.

Bedenne.

J Clin Oncol. 2007 Apr 1;25(10):1160-8.

Patients received fluorouracil (FU) and cisplatin and either

conventional (46 Gy) or split-course (15 Gy X 2) concomitant

radiotherapy. Then randomly assigned to surgery (arm A) or

continuation of chemoradiation (arm B;FU/cisplatin and either

conventional [20 Gy] or split-course [15 Gy] radiotherapy).

Results Surgery Radiation

Survival/2y 34% 40%

Median Surv 17.7 mos 19.3 mos

Local Control 66% 57%

Stent 5% 32%

Chemoradiation followed by surgery compared with chemoradiation

alone in squamous cancer of the esophagus: FFCD 9102.

Bedenne.

J Clin Oncol. 2007 Apr 1;25(10):1160-8.

T4b

Chemoradiation

Palliative Care

Chemo alone or

Radiation alone

Inoperable

Palliative Radiation

Improvements in Swallowing

(dysphagia)

Outcome Radiation Radiation + ChemoRx

survival 203 days 210 days

improved dysphagia (swallowing)

9 weeks 68% 74%

6 months 31% 33%

ASTRO 2014 (CT-03)

CT Scan showing complete

disappearance of a large squamous

cancer in upper esophagus

PET scan

before and

two months

after

completing

radiation, the

PET may

continue to

show

improvement

for several

months

The same patient at 7 months, with the PET scan

totally negative, large tumors may take a longer

time to respond completely, especially

adenocarcinoma

PET Scans – 3 Months after Chemoradiation

for small squamous cancer in mid esophagus,

cancer no longer visible by three months

Prior to Radiation 3 Months afterRadiation Boost

Target

Radiation Technique

CT scan is obtained at the time of

simulation

CT images are then imported

into the treatment planning

computer

In the simulation

process the CT

and other images

are used to create

a computer plan

www.rtog.org

How big should the radiation

target be?

Advice from the RTOG

RTOG 1010

HER2 + Adenocarcinoma of the

Esophagus

1. PreOp Chemoradiation

Carbo/Taxol +/- Herceptin

Radiation (50.4Gy)

2. 5 – 8 weeks later surgery

RTOG 1010 Target

1.GTV (Gross Tumor Volume) = gross cancer

and obviously involved nodes

2. CTV (Clinical Tumor Volume) = GTV + 4cm

above and below and 1.0 – 1.5cm radial

margins, plus para-esophageal or celiac

lymph node axis

3. PTV (Planning Target Volume) = GTV + 0.5

– 1cm expansion

Dose: 50.4Gy in 28 fractions (45Gy + 5.4 Gy

as boost)

Start with PET – CT images of Cancer Target

Cancer

Identify the Gross Tumor Volume (GTV)

GTV

Identify the Clinical Tumor Volume (CTV)

CTV

Identify the Planning Tumor Volume (PTV)

PTV

Identify the Normal Structures that Might be Affected

Lung Lung

Heart

Liver

Kidney

Spinal Cord

Kidney

Spinal Cord

Radiation

IMRT (Tomotherapy) Plan

PTV

radiation

Risk of Lymph Node Spread for

Adenocarcinoma of the Esophagus based

on depth of invasion

Radiation Target Advice on the

Lymph Nodes from the NCCN

Cervical Esophagus: include

supraclavicular and possible

cervical nodes

Proximal Third: supraclavicular

and para-esophageal

Middle Third: para-esophageal

Distal Third/GE Junction: para-

esophageal, lesser curvature,

celiac axis

Esophagus

Cancer

Lymph Nodes

Esophagus Cancer Lymph Nodes

Incidence of Lymph Node Metastases for

Squamous Cancer

Upper Middle Lower

Incidence of Lymph Node Metastases for

Squamous Cancer

Incidence of Lymph Node Metastases for Adenocarcinoma

GE Junction Distal

Typical Radiation Field for Cervical

or Upper Esophagus

radiation

Typical Radiation Field for Middle

Esophagus

Typical Radiation Field for Lower

Esophagus

Typical Radiation Field for Lower

Esophagus

Radiation Dose Guidelines

from the NCCN

PreOperative: 41.1 – 50.4Gy (1.8-

2.0/day)

PostOperative: 45 – 50.4Gy (1.8-

2.0/day)

Definitive: 50 – 50.4Gy (1.8-2.0/day)

- higher dose (60-66Gy) may be considered in

cervical esophagus where surgery is not

planned, but there is little evidence of benefit >

50.4Gy

Normal

Structure

Dose Limits

from the

RTOG 1010

Limits of Radiation to Normal

Structures, Advice from the NCCN

Lung: V20 to <20% and then V10 to

<40%

Liver: 60% liver < 30Gy

Kidneys: at least 2/3 of one < 20Gy

Spinal Cord: < 45Gy

Heart: 1/3 < 50Gy

Lung and

Trachea

Heart

Esophagus

Spinal Cord

Stomach

Side Effects

Structures

affected

by

radiation

Lung and

Trachea

Heart

Esophagus

Spinal Cord

Stomach

Side Effects

Structures

affected

by

radiation

Radiation to the lung and trachea can lead to

coughing, or shorteness of breath, if the

esophagus cancer is invading into the trachea

there is a risk of a fistula (TE fistula)

Long terms risks are related to scarring or fibrosis

in the lung which can cause breathing problems

Lung and

Trachea

Heart

Esophagus

Spinal Cord

Stomach

Side Effects

Structures

affected

by

radiation

Radiation to the esophagus may temporarily

increase the problems with swallowing (> 75%)

and long term there is a risk of stenosis or

narrowing (stricture in 15 – 20% requiring dilation)

Lung and

Trachea

Heart

Esophagus

Spinal Cord

Stomach

Side Effects

Structures

affected

by

radiation

Other common side effects include skin irritation

(sun burn), fatigue, loss of appetite and nausea

There is a small risk of injury to other organs near

by e.g. the spinal cord, liver, stomach or kidneys

Results with Radiation Alone

In general the median survival is only 6 to 12

months and the 5 year survival is < 10%)

In a large series ( >8,400 patients) survival was:

18%/1y, 8%.2y and 6%/5y

In another large series (9,511) the 5 year survival

was 5.8%

In another series by stage: I: 20%/5y, II: 10%/5y,

III: 3%/5y and IV: 0%

Chemoradiotherapy of locally advanced esophageal

cancer: long-term follow-up of a prospective

randomized trial (RTOG 85-01).

Treatment 5 Year Survival

Radiation Alone 0%

Chemo-Radiation 14 – 26%

Palliation from Radiation

60 – 80% will have improvement in

swallowing

With radiation alone: 71%,

Chemoradiation was: 88%

Coia. Cancer 1993;71:281

www.aboutcancer.com

Cancer of the Esophagus

Radiation