The role of radiation therapy in the treatment of pancreas cancer

1. Radiation for Cancer
of the Pancreas
www.aboutcancer.com

2. rtog.org
Radiation Therapy Oncology Group (RTOG)

3. NCCN.org
National Comprehensive Cancer Network (NCCN)

5. Summary of Treatment
1.Resection is the only chance for a cure, and
resectable patients show undergo surgery
without delay followed by adjuvant therapy
2.Borderline resectable patients may benefit
from neoadjuvant therapy and then surgery
3.Unresectable patients may benefit from
chemotherapy or chemoradiation
4.Metastatic disease may benefit from
chemotherapy or other palliative treatments

6. Survival
Surgery offers the only cure, but only 10-20%
are candidates and the 5 year survival is only
20% and median 13-20 months
Locally advanced the median survival is 8-14
months
Up to 60% already have metastases and
survival of 4 to 6 months

7. Patterns of Failure after
Surgery
After surgery local relapse rate of 50
– 86%
and distant recurrence rate of 40 –
90%

8. RTOG 9704
postOp FU then chemoradiation versus
Gemcitabine then chemoradiation
(50.4Gy)
Slight advantage to the Gemzar arm for
head of pancreas group: median survival
of 20.5 months versus 17.1 months and
long term 22%/5y versus 18%/5y

9. Is there a proven role for postOp
radiation?
• European studies (CONKO 001 Trial, EORTC
Trial, ESPAC-1 showed benefit from
chemotherapy but no benefit or in fact harm
from including radiation and so they favor
chemotherapy alone
• American Trials (GITSG) showed benefit and
favor including radiation

10. Benefits from Adjuvant Radiation
GITSG
postOp 40Gy + 5FU versus observation
The radiation arm had better median survival (20 mos versus 11 mos)
and 2 year survival 20% versus 10%
EORTC
postOp 5FU versus chemorad (40Gy in split course) and better 2Y
survival in radiation arm: 34% versus 26%
NCDB review
chemoradiation improved survival (HR .784) but no chemoRx (1.08)
Hopkins/ Mayo Clinic Review (Hsu, 2008) n = 1.045
Adjuvant 5FU/XRT improved survival from 16.3 months to 22.5
months

11. Adjuvant Radiotherapy and Chemotherapy
for Pancreatic Carcinoma: The Mayo Clinic
Experience (1975-2005)
review 472 consecutive patients who
underwent complete resection with negative
margins (R0) for invasive carcinoma (T1-3N0-
1M0)
Surgery S + Chemoradiation
Overall survival 19.2 mos 25.2 mos
Survival 39%/2y 50%/2y
15%/5y 28%/5y
JCO July 20, 2008:3511-3516

12. Adjuvant Chemotherapy and Radiation Large,
Prospectively Collected Database at the Johns
Hopkins Hospital /The final cohort includes 616
patients.
JCO July 20, 2008:3503-3510
Surgery S + Chemoradiation
Median Survival 14.4 mos 21.2 mos
Survival 31.9%/2y 43.9%/2y
15.4%/5y 20.1%/5y

13. Study number median 2y 5y
GITSG
chemoradiation 21 20.0 mos 42% 15%
observation 22 10.9 mos 15% 5%
chemoradiation 30 18.0 mos 46% 17%
EORTC
chemoradiation 110 21.6 mos 51% 25%
observation 108 19.2 mos 41% 22%
ESPAC-1
chemotherapy 147 20.1 mos 40% 21%
no chemo 142 15.5 mos 30% 8%
chemoradiation 145 15.9 mos 29% 10%
no chemorad. 144 17.9 mos 41% 20%
RTOG-9704
gemzar – chemorad 187 20.5 mos 31%/3 22%
5-FU – chemorad 201 17.2 mos 22%/3y 18%
Prospective Trials of Adjuvant Therapy

14. RTOG 0848 Adjuvant
Step 1: Adjuvant chemotherapy: (Arm1
Gemcitabine X 5 or Arm 2
Gemcitabine + Erlotinib X 5))
Step2: In no progression then: (Arm 3
one more cycle of chemo or Arm 2 1
cycle then chemoradiation with either
capecitabine or 5-FU)
Radiation dose is 1.8Gy X 28 (50.4Gy)

15. RTOG 0848 Adjuvant

16. NCCN Adjuvant

17. Summary of Treatment
1.Resection is the only chance for a cure, and
resectable patients show undergo surgery
without delay followed by adjuvant therapy
2.Borderline resectable patients may benefit
from neoadjuvant therapy and then surgery
3.Unresectable patients may benefit from
chemotherapy or chemoradiation
4.Metastatic disease may benefit from
chemotherapy or other palliative treatments

18. Neoadjuvant Therapy (chemo or
radiation prior to surgery)
-About 1/3 of patients have a long delay after
surgery getting started on PostOp therapy
- 20-40% who get preOp will be found to
develop Mets and avoid surgery
-PreOp may increase the number of surgical
candidates
-No good randomized Trials
-Some trials the 5 year survival in those
undergoing a curative resection in the 32 – 36%
range

19. SEER Data Base
3,885 Resectable Pancreas
Cancer
Treatment Number Median Survival
Neoadjuvant XRT 70 (2%) 23 months
PostOp XRT 1,478 (38%) 17 months
Surgery Only 2,337 (60%) 12 months
. Int J Radiat Oncol Biol Phys2008;72(4):1128–1133.

20. Summary of Treatment
1.Resection is the only chance for a cure, and
resectable patients show undergo surgery
without delay followed by adjuvant therapy
2.Borderline resectable patients may benefit
from neoadjuvant therapy and then surgery
3.Unresectable patients may benefit from
chemotherapy or chemoradiation
4.Metastatic disease may benefit from
chemotherapy or other palliative treatments

21. Radiation for Unresectable
Pancreas Cancer
ECOG Trial, Loehrer 2011)
Therapy Median Survival
Gemzar 9.2 months
Gemzar + Radiation 11.1 months
Michigan Trial / IMRT 55Gy + Gemzar, Ben-Josef 2012
Therapy Survival
Historical 11.2 months 13%/2y
IMRT 14.8 months 30%/2y

22. Survival in ECOG Trial
JCO November 1, 2011vol. 29 no. 31 4105-4112
Chemo + Radiation
Chemo

23. Median Survival in Months
Inoperable Pancreas Cancer
Gemzar Alone 9.1 – 9.9
Gemzar + Radiation 11.3 – 11.9
JCO November 1, 2011vol. 29 no. 31 4105-4112

24. RTOG 1201 Unresectable
Three Arms ChemoRx Radiation
1 gemcitabine X 12w 63Gy (IMRT) + capecitabine
2 gemcitabine X 12w 50.4Gy (3D) + capecitabine
3 FOLFIRINOX X 12w 50.4Gy (3D) + capecitabine
IMRT Dose is 2.25Gy X 28 (63Gy) / 3D Dose is 1.8 Gy X 28 (50.4Gy)
95% of the PTV must get 95% of the prescribed dose and the Dmax to
0.03cc is no higher than 110% of the prescription dose

26. NCCN Inoperable

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

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

29. www.rtog.org

30. The CT Images Are Contoured and
Labelled to Identify The Structures

31. Typical Radiation Fields

32. Radiation Fields

33. Computer Reconstruction from the CT Scan

34. Cancer
Pancreas
Liver
Kidney Kidney
Stomach
Computer Reconstruction from the CT Scan

35. Computer Reconstruction from the CT Scan
Lymph
Nodes

36. Computer Reconstruction from the CT Scan
Radiation
Zone

37. Computer Reconstruction from the CT Scan
Small
Bowel
Colon

38. Computer Reconstruction from the CT Scan
Multiple structures (Liver, Stomach, Small Bowel, Colon, Spinal
Cord, Kidneys) can all be effected by the radiation field

39. Pancreas Atlas for
PostOp Radiation

40. PV – Portal Vein
PJ – Pancreaticojejnosotomy
SMA – Superior Mesenteric
Artery
CA – Celiac Artery

41. Computer Generated Radiation
Targets

42. Radiation
1.Patients are usually treated daily,
Monday through Friday for about 5
weeks
2.Dose of inoperable patients is 45-
54Gy (1.8 – 2.5Gy/fx) or 36Gy (2.4
fx)
3.PostOp patients 45-46Gy (1.8 –
2Gy/fx) with possible 5 – 9Gy
boost

43. Normal Tissue Dose Limits

44. Normal Tissue Dose Limits

45. Side Effects of Pancreas
Radiation

46. bowel kidneykidney
stomach pancreas
Side Effects of Pancreas
Radiation
liver

47. Side Effects of Pancreas
Radiation
• Fatigue
• Loss of appetite
• Diarrhea
• Skin Irritation
Long Term:
Depending on the dose to other organs, there
is a small risk of bowel damage or decreased
function from the liver or kidneys

48. Radiation for Cancer of the
Pancreas
www.aboutcancer.com