Borderline Resectable Pancreatic Cancer Mekhail Anwar MD PhD and - - PowerPoint PPT Presentation

Borderline Resectable Pancreatic Cancer

Mekhail Anwar MD PhD and Matt Susko MD MS {mekhail.anwar@ucsf.edu, matthew.susko@ucsf.edu} University of California – San Francisco Department of Radiation Oncology

Case Presentation

63 y/o male with painless jaundice, intermittent epigastric pain and 25 lbs weight loss over 6 months. Exam: Thin slightly jaundiced male. Labs: AST/ALT – 65/83 ALKP - 320 Tbili – 7.5 CA 19-9 - 276 CEA - 1.7 Imaging Workup: EUS/biopsy – Pancreatic Adenocarcinoma PET/CT – No distant metastatic disease Pancreatic Protocol CT …

Initial Diagnostic CT Imaging

• Mass in the pancreatic head and uncinate process with

associated pancreatic and intrahepatic ductal dilation

• The mass partially surrounds the proximal portal vein,

abuts the celiac artery and SMA and left renal vein

Borderline Resectable

Solid tumor contact with

• 1. CHA without extension

to CA or hepatic artery bifurcation

• 2. SMA ≤180°
• 3. CA ≤180°
• 4. SMV or PV of >180°,

contact of ≤180° with contour irregularity of the vein

• 5. Inferior vena cava (IVC)

Synergistic Strategies

• 1. Surgery:

Local, Curative

• 3. Systemic

Systemic + Local

• 2. Local (RT)

Local (+Systemic?) Survival

Surgery: Striving for an R0 Resection

How can we maximize opportunity for R0 resection?

Detmir et al. Ann. Surg 2017 Chang et al. JCO 2009

R0 R0

Question: Initial Management

In this borderline resectable pancreatic cancer patient, what would your preferred course of management be?

• A. Chemotherapy alone; no role for local therapy.
• B. Chemoradiation followed by surgery.
• C. Chemotherapy followed by surgery
• D. Chemotherapy, chemoradiation/SBRT, followed by surgery.
• E. Surgery followed by chemoradiation and/or chemotherapy.

Chemoradiation Upfront

PREOPANC-1

• Arm A: Surgery → CRT → CTx
• Arm B: CRT → Surgery → CTx
• CRT
• 36 Gy (2.4 Gy x 15 fx)
• Weekly gemcitabine
• 246 patients

Results

Arm A Arm B

N 127 119 OS 13.5 mo 17.1 mo Resected 72% 62% % R0 31 65 LRFI 11.8 mo NR OS (resected) 16.8 mo 42.1 mo

Chemotherapy

Identifies patients likely to development metastases or progress in short interval1

• 30-40% of patients progress within 3-4 months when treated with

chemotherapy alone

Is neoadjuvant chemotherapy sufficient?2

• Retrospective review of FOLFIRINOX with or without RT
• 26 patients, 22 treated with chemotherapy alone
• 90% R0 resection rate with FOLFIRINOX alone, addition of CRT led to 100%

Evans grade III-IV specimens

Hammel et al. JAMA 2016. (LAP 07) Kim et al. J Surg Onc 2016

Combination therapy: Neoadjuvant CTx + RT

• FOLFIRINOX + Chemoradiation 1
• 15/22 underwent resection, 14/15 were R0 resections
• 5 patients with <5% residual tumor and 2 with complete pathologic

response

• Chemotherapy with adaptive radiation therapy2
• 48 patients with 8 cycles neoadjuvant FOLFIRINOX, RT based on evidence of

persistent vessel involvement

• If involvement à CRT
• If no involvement à hypofractionated RT
• 32/48 underwent resection, 31/32 were R0 resections
• Key Questions
• Alliance Trial – CRT vs SBRT?
• Response Assessment - Optimizing imaging strategies
• 1. Katz et al. JAMA Surgery 2016
• 2. Murphy et al. JAMA Oncology 2018

Response to Neoadjuvant FOLFIRINOX

• Completed 12 cycles of FOLFIRNIOX
• Labs: Normalized
• AST/ALT – 35/42 ALKP – 80 Tbili – 1.6 CA 19-9 - 32 CEA - 1.6
• Re-staging Imaging
• Slight interval decrease in size of primary pancreatic mass and retroperitoneal and

peripancreatic lymphadenopathy.

• No contact with SMA or Celiac

Role of Radiation Therapy

In this case of a patient with borderline pancreatic cancer, with a durable response to chemotherapy, what is the role of radiation therapy?

• A. There is no role for radiation therapy. Proceed to surgical

evaluation.

• B. SBRT, then surgery.
• C. Chemoradiation, then surgery.

How does this change if there is persistent vascular involvement?

Comments and Discussion

Chemoradiaton Korean Study (MA)