The role of radiation therapy in the treatment of esophagus cancer

1. Cancer of the Esophagus
Radiation
www.aboutcancer.com

2. T1bN+ or
T2-T4a
PreOp
Chemoradiation
then Surgery
Chemoradiation
Most locally
advanced
esophagus cancers

3. 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%

4. Survival
CRT + Surgery
Surgery
Months

5. Comparison of Preoperative Chemotherapy
Compared With Preoperative
Chemoradiotherapy
JCO February 20, 2009 vol. 27 no. 6 851-856
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%.

6. Comparison of Preoperative Chemotherapy Compared
With Preoperative Chemoradiotherapy
Arm B chemo + radiotherapy and
surgery):
Arm A chemotherapy and surgery
JCO February 20, 2009vol. 27 no. 6 851-856

7. T1bN+ or
T2-T4a
PreOp
Chemoradiation
then Surgery
Chemoradiation
Most locally
advanced
esophagus cancers
Can you skip the surgery?

8. 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%

9. RTOG 94-05
J 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%

10. Survival from 94-05
50.4Gy
64.8Gy
Months

11. 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.

12. ChemoRadiation Alone,
RTOG
Survival
Months
RTOG 0113
RTOG 9405
JCO 2008;28:4551

13. Survival with ChemoRadiation
versus Esophagectomy
Chan. IJROBP ;1999:45:265

14. 10y Survival Chemoradiation
with or without Surgery
No Surgery
2 4 6 8 10
Years
Surgery
Bidoli. Cancer 2002:94:352

15. 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).

16. 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%

17. Treatment-related mortality was significantly increased
in the surgery group than in the chemoradiotherapy
group
Treatment Mortality
Surgery 12.8%
ChemoRad 3.5%

18. Survival
J Clin Oncol. 2005 Apr 1;23(10):2310-7
Years
Surgery
Radiation

19. 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%

20. 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.

21. T4b
Chemoradiation
Chemo alone or
Radiation alone
Palliative Care
Inoperable

22. 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)

23. CT Scan showing complete
disappearance of a large squamous
cancer in upper esophagus

24. PET scan
before and
two months
after
completing
radiation, the
PET may
continue to
show
improvement
for several
months

25. The same patient at 7 months, with the PET scan
totally negative, large tumors may take a longer
time to respond completely, especially
adenocarcinoma

26. PET Scans – 3 Months after Chemoradiation
for small squamous cancer in mid esophagus,
cancer no longer visible by three months
Prior to Radiation Radiation Boost 3 Months after
Target

27. Radiation Technique

28. CT scan is obtained at the time of
simulation
CT images are then imported
into the treatment planning
computer

29. In the simulation
process the CT
and other images
are used to create
a computer plan

30. www.rtog.org

36. How big should the radiation
target be?
Advice from the RTOG

37. RTOG 1010
HER2 + Adenocarcinoma of the
Esophagus
1. PreOp Chemoradiation
Carbo/Taxol +/- Herceptin
Radiation (50.4Gy)
2. 5 – 8 weeks later surgery

38. 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)

39. Start with PET – CT images of Cancer Target
Cancer

40. Identify the Gross Tumor Volume (GTV)
GTV

41. Identify the Clinical Tumor Volume (CTV)
CTV

42. Identify the Planning Tumor Volume (PTV)
PTV

43. Identify the Normal Structures that Might be Affected
Lung Lung
Heart
Liver
Kidney
Spinal Cord
Kidney
Spinal Cord
Radiation

44. IMRT (Tomotherapy) Plan
PTV
radiation

45. Risk of Lymph Node Spread for
Adenocarcinoma of the Esophagus based
on depth of invasion

46. 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

47. Esophagus
Cancer
Lymph Nodes

48. Esophagus Cancer Lymph Nodes

49. Incidence of Lymph Node Metastases for
Squamous Cancer
Upper Middle Lower

50. Incidence of Lymph Node Metastases for
Squamous Cancer

51. Incidence of Lymph Node Metastases for Adenocarcinoma
GE Junction Distal

53. Typical Radiation Field for Cervical
or Upper Esophagus
radiation

54. Typical Radiation Field for Middle
Esophagus

55. Typical Radiation Field for Lower
Esophagus

56. Typical Radiation Field for Lower
Esophagus

57. 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

58. Normal
Structure
Dose Limits
from the
RTOG 1010

59. 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

60. Side Effects
Lung and
Trachea
Heart
Esophagus
Spinal Cord
Stomach
Structures
affected
by
radiation

61. Side Effects
Lung and
Trachea
Heart
Esophagus
Spinal Cord
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)
Stomach
Structures
affected
by
radiation
Long terms risks are related to scarring or fibrosis
in the lung which can cause breathing problems

62. Side Effects
Lung and
Trachea
Heart
Esophagus
Spinal Cord
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)
Stomach
Structures
affected
by
radiation

63. Side Effects
Lung and
Trachea
Heart
Esophagus
Spinal Cord
Other common side effects include skin irritation
(sun burn), fatigue, loss of appetite and nausea
Stomach
Structures
affected
by
radiation
There is a small risk of injury to other organs near
by e.g. the spinal cord, liver, stomach or kidneys

64. 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%

65. 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%

66. Palliation from Radiation
60 – 80% will have improvement in
swallowing
With radiation alone: 71%,
Chemoradiation was: 88%
Coia. Cancer 1993;71:281

67. Cancer of the Esophagus
Radiation
www.aboutcancer.com