Radiation for Cancer of the

Pancreaswww.aboutcancer.com

rtog.org

Radiation Therapy Oncology Group (RTOG)

NCCN.org

National Comprehensive Cancer Network (NCCN)

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

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

Patterns of Failure after Surgery

After surgery local relapse rate of 50 – 86%

and distant recurrence rate of 40 – 90%

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

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

Benefits from Adjuvant Radiation

GITSGpostOp 40Gy + 5FU versus observation

The radiation arm had better median survival (20 mos versus 11 mos) and 2 year survival 20% versus 10%

EORTCpostOp 5FU versus chemorad (40Gy in split course) and better 2Y survival in radiation arm: 34% versus 26%

NCDB reviewchemoradiation improved survival (HR .784) but no chemoRx (1.08)

Hopkins/ Mayo Clinic Review (Hsu, 2008) n = 1.045Adjuvant 5FU/XRT improved survival from 16.3 months to 22.5 months

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

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

Study number median 2y 5y

GITSGchemoradiation 21 20.0 mos 42% 15%observation 22 10.9 mos 15% 5%chemoradiation 30 18.0 mos 46% 17%

EORTCchemoradiation 110 21.6 mos 51% 25%observation 108 19.2 mos 41% 22%

ESPAC-1chemotherapy 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-9704gemzar – chemorad 187 20.5 mos 31%/3 22%5-FU – chemorad 201 17.2 mos 22%/3y 18%

Prospective Trials of Adjuvant Therapy

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)

RTOG 0848 Adjuvant

NCCN Adjuvant

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

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

SEER Data Base3,885 Resectable Pancreas Cancer

Treatment Number Median Survival

Neoadjuvant XRT 70 (2%) 23 monthsPostOp XRT 1,478 (38%) 17 monthsSurgery Only 2,337 (60%) 12 months

. Int J Radiat Oncol Biol Phys2008;72(4):1128–1133.

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

Radiation for Unresectable Pancreas Cancer

ECOG Trial, Loehrer 2011)

Therapy Median Survival

Gemzar 9.2 monthsGemzar + Radiation 11.1 months

Michigan Trial / IMRT 55Gy + Gemzar, Ben-Josef 2012

Therapy Survival

Historical 11.2 months 13%/2yIMRT 14.8 months 30%/2y

Survival in ECOG Trial

JCO November 1, 2011vol. 29 no. 31 4105-4112

Chemo + RadiationChemo

Median Survival in Months Inoperable Pancreas Cancer

Gemzar Alone 9.1 – 9.9Gemzar + Radiation 11.3 – 11.9

JCO November 1, 2011vol. 29 no. 31 4105-4112

RTOG 1201 Unresectable

Three Arms ChemoRx Radiation

1 gemcitabine X 12w 63Gy (IMRT) + capecitabine2 gemcitabine X 12w 50.4Gy (3D) + capecitabine3 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

NCCN Inoperable

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

The CT Images Are Contoured and Labelled to Identify The Structures

Typical Radiation Fields

Radiation Fields

Computer Reconstruction from the CT Scan

CancerPancreas

Liver

Kidney Kidney

Stomach

Computer Reconstruction from the CT Scan

Computer Reconstruction from the CT Scan

Lymph Nodes

Computer Reconstruction from the CT Scan

RadiationZone

Computer Reconstruction from the CT Scan

SmallBowel

Colon

Computer Reconstruction from the CT Scan

Multiple structures (Liver, Stomach, Small Bowel, Colon, Spinal Cord, Kidneys) can all be effected by the radiation field

Pancreas Atlas for PostOp Radiation

PV – Portal VeinPJ – PancreaticojejnosotomySMA – Superior Mesenteric ArteryCA – Celiac Artery

Computer Generated Radiation Targets

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

Normal Tissue Dose Limits

Normal Tissue Dose Limits

Side Effects of Pancreas Radiation

bowel kidneykidney

stomach pancreas

Side Effects of Pancreas Radiation

liver

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

Radiation for Cancer of the Pancreas

www.aboutcancer.com