Radiation Therapy for Pancreatic Cancers Eyad Abu-Isa, M.D.
Assistant Professor, Radiation Oncology University of
Michigan/Providence Cancer Institute February 28, 2015 Slide 2 EA
2015 Disclosures I have no actual or potential conflict of interest
in relation to this presentation. Slide 3 EA 2015 Overview
Radiation Basics Review of Literature Resected Unresectable
Radiation Techniques Future Directions Questions Slide 4 EA 2015
Varian Truebeam Slide 5 EA 2015 How radiation therapy works Slide 6
EA 2015 Resected: Adjuvant Treatment Slide 7 EA 2015 Kalser and
Ellenberg, Arch Surg 1985. GITSG 9173 Methods: Patients: 43 total
patients enrolled 22 patients randomized to no adjuvant treatment,
and 21 to chemoradiation 68% underwent Whipple, 32% had total
pancreatoduodenectomy. All but 2 patients had head lesions. Tumors:
All patients underwent resection of localized pancreas cancer, and
all had NEGATIVE MARGINS. 35% tumor confined to pancreas, 37% tumor
extended beyond the pancreas, 28% had nodal involvement Slide 8 EA
2015 GITSG 9173 Methods: Treatment Arms: Arm 1) No adjuvant therapy
Arm 2) Chemoradiotherapy arm: Chemotherapy: 5-FU (500mg/m 2 ) given
as bolus infusion on day 1,2,3 of radiation courses one and two,
and once weekly for two years or until recurrence documented.
Radiation Therapy: Two 20 Gy courses, separated by two weeks.
Fraction dose not specified. Slide 9 EA 2015 GITSG 9173 Results:
Adjuvant chemoRT significantly improves median survival and DFS.
Adjuvant TxMedian Survival (P=0.03) 2 yr survival Median DFS
(P=0.01) None11 months15%9 months ChemoXRT20 months42%11 months
Slide 10 EA 2015 Resected: Adjuvant Treatment Slide 11 EA 2015
ESPAC Purpose: To clarify benefits of chemoRT and maintenance chemo
in adjuvant setting Methods: Prospective, multi-institutional,
semi- randomized, semi- controlled trial. Primary endpoint: death.
Patients: 541 patients were enrolled with histologically proven
ductal adenocarcinoma, with gross total resection and no evidence
of local spread or distant metastasis. Tumors: Allowed (+) margins
Neoptolemos JP, Lancet 2001. Slide 12 EA 2015 ESPAC 2 x 2 factorial
design (285 pt subset) Treatment# PatientsMedian Survival (mo.)
Chemoradiation14215.8 No chemoradiation14317.8 (NS) Treatment#
PatientsMedian Survival Chemotherapy14620 No Chemotherapy13918 (SS)
Slide 13 EA 2015 Resected: Adjuvant Treatment Slide 14 EA 2015
CONKO-001 Oettle et al. JAMA 2007 Phase III, multicenter,
randomized, controlled trial Stratified for resection, tumor, and
node status 368 pts with R0 (80%) or R1 pancreatic resection, T1-4
(82% T3), N0-1 (70% N1) Observation vs Gemcitabine 1000 mg/m2 x 6
cycles (days 1, 8, 15 q4 weeks) Slide 15 EA 2015 CONKO-001 Results:
Gemcitabine improved DFS Median f/u 53 months Median DFS: 13.4 vs
6.9 months (p EA 2015 MDA Experience Prospective study of 132
consecutive patients who received preop chemoradiation followed by
Whipple RT: 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28
fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions Chemo:
concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or
gemcitabine). Then restaging studies--> if no evidence of
disease progression, then Whipple. Results: 2YS 40% and MS was 21
months, despite 43% requiring vascular resections Rate of clear
resections: 88% Rate of local recurrence: 6% Breslin, Ann Surg Onc,
2001 Slide 27 EA 2015 Radiation Planning Slide 28 EA 2015 Motion
assessment/control Methods of diaphragmatic motion control ABC
breath hold (if tolerated) scan on expiration Others use abdominal
compression If ABC not tolerated, 4D CT to accurately account for
motion Treatment planning CT scan is fused with diagnostic study
(PET/CT, MRI, CT) Slide 29 EA 2015 Radiation Techniques Avoidance
organs: duodenum/small bowel, liver, kidneys, spinal cord
Pancreatic head lesions: include pancreaticoduodenal,
suprapancreatic, celiac nodes, porta hepatis, duodenal loop
Body/tail lesions: pancreaticoduodenal, lateral suprapancreatic,
splenic hilar nodes Boderline/Unresectable patients: small field
radiation to gross disease only. Slide 30 EA 2015 Radiation Targets
TargetPancreatic headPancreatic tailUnresectable/Bo rderline
Primary tumorxxx Positive LNsxxx Parapanc LNsxx Pancduo LNsxx
Celiac/SMA LNsxx Portal LNsx Splenic LNsx Avoidance organs:
duodenum/small bowel, liver, kidneys, spinal cord Slide 31 EA 2015
2D Radiation Techniques AP field with blocking for pancreatic head
lesions Lateral field with blocking Slide 32 EA 2015 Intensity
Modulated RT (IMRT) Slide 33 EA 2015 High activity low-dose rate
brachytherapy Single or multiple high activity radioactive I-125
seeds are placed into a tumor under radiographic guidance.
Advantages over external beam: Low energy radiation emitted from
inside out, meaning high dose to tumors, with quick dose fall-off
Continuous low dose radiation delivered over months, potential
biologic advantage Slide 34 EA 2015 HALDR 66 yo male with
pancreatic tail adenocarcinoma. Slide 35 EA 2015 X Pancreas tail
mass (red) and intended seed position (X). No direct access in the
axial plane due to obstruction by kidney(K), spleen(S), and
bowel(B). K S B Figure 2 Slide 36 EA 2015 Needle access plane
(green transparency) 2.4 cm below axial target slice Slide 37 EA
2015 K S Needles advanced in a non-axial superior direction at the
junction of the kidney and spleen. After passage beyond the
critical organ it is again possible to angle the needle in the
intended direction. Once past the organ the needle can safely
displace the organ (spleen in the example) Slide 38 EA 2015 Coaxial
needle in position (blue arrow). Marker seed in place (red arrow)
Slide 39 EA 2015 Marker seed (red arrow) and radioactive seed (gold
arrow) near intended position Slide 40 EA 2015 Before After
Response to HALDR Slide 41 EA 2015 Conclusions Pancreatic survival
rates are low, highlighting the need for future research. Role for
adjuvant radiation treatment is controversial, but with careful
radiation planning proper patient selection, and better systemic
therapy, a benefit may exist Radiation improves local control in
patients with borderline resectable and unresectable disease and
may impact survival. Slide 42 EA 2015 Thank you!
