Diagnosis and Management of Pancreatic Carcinoma - Best ... Staging...The pancreatic head is richly innervated by autonomic nerve fibers coming from the celiac plexus (R and L celiac

Diagnosis and Management of Pancreatic Carcinoma - Best Practice, Pearls and Pitfalls

ZAHRA KASSAMSouthwest Regional Imaging Lead, Cancer Care Ontario

Assistant Professor of Medical Imaging and OncologySchulich School of Medicine, Western University

What the Radiologist Needs to Know in 2016

Objectives

Review 2014 SAR/APA recommendations for Pancreatic Adenocarcinoma (PAC) on CT - protocol,

staging, and reporting guidelines

Discuss results of LHIN-2 Retrospective Review with emphasis on importance of multidisciplinary

discussion

Review approaches for staging of suspected PAC that is not clearly biopsy-proven.

Pancreatic Adenocarcinoma –

Biology, Anatomy and CT Staging

Pancreatic carcinoma is a lethal disease -the only beneficial Rx is surgery with

negative margins (R0)

Despite “successful” surgery, virtually all patients will die from their disease

Biology is everything

Whipple ResectionModern Surgical Results

• Marked reduction in post-op mortality (1-3%) at large centers

• Continued high morbidity even at high volume centers (20-40%)

Why is pancreatic carcinoma such a fatal disease?

Vague symptoms

Lack of biomarkers

for early detection

Lack of effective systemic therapy

Basic Biology• Early, preclinical

dissemination

• Disease often systemic at presentation

What is the role of the radiologist?

Ensure protocols are optimized

Ensure consistent, reproducible imaging

Interpretation according to established guidelines

• 2014 APA/SAR Consensus Statement

• Terminology we all understand and agree upon

• What constitutes a resectable or unresectable tumor?

Categorize the lesion for our clinical colleagues

• Resectable, locally advanced, or unresectable?

Encasement with

deformity

Abutment, no

deformity

Encasement, no

deformity

• No extension to celiac, CHA, SMA, SMV-PV confluence

• No distant metastasis

• Stage I, II (T1-3, Nx, M0)

Short segment venous involvement with option for reconstruction

• GDA encasement up to HA without extension to celiac axis

• SMA abutment (<1800)

Celiac, SMA encasement (> 1800)

• Stage III (T4, Nx, M0)

T

Resectable

T

LocallyAdvanced

T

BorderlineResectable




• Celiac, SMA encasement (> 1800)


• Short segment venous involvement with option for reconstruction



NCCN criteria




Short segment venous involvement with option for reconstruction



Celiac, SMA encasement (> 1800)


T

Resectable

T

LocallyAdvanced

T

BorderlineResectable

An all too familiar story59 yo male with abdominal pain and jaundice

Lesion confined to pancreas, no vascular involvement

3.2 cm

Slide courtesy of Dr. R. B. Jeffrey, Stanford University

• R0 resection: Expired in 11 mos

• Path: Perineural invasion, macroscopic duodenal invasion

• Both are key prognostic features

What is Perineural Invasion (PNI)?

Dissemination of tumor within the potential space between the nerve

fiber and its sheath:

perineural space

Characteristic mode of spread of pancreatic cancer, rarely seen in

other GI tumors

Occurs in 70% to 100% of pancreatic cancers; reported in

lesions as small as 2 mm

N

N

Why is PNI important?

Occurs very early in the disease, leading to systemic spread

• Anoxic environment - Spread via nerve fascicles is optimal for tumor growth

• Refractory to chemo and XRT

Clinical pearl

• Affected patients often present with pain

• (As opposed to “painless jaundice”)

PNI is a major factor in the failure of surgery & mortality of pancreatic cancer

Biomarker of reduced survival

It is incredibly easy to miss on CT!

The radiologist must know where to look.

Peripancreatic Neural Plexi

The pancreatic head is richly innervated by autonomic nerve fibers coming from the celiac plexus (R and L celiac ganglia)

and superior mesenteric ganglion.

These nerve plexi surround the SMA and are interposed between the

pancreas and the artery.

The intricate neural network serves as a conduit for retrograde spread of

pancreatic cancer.

Celiac

ganglion

SMA

ganglion

Blood Supply - Pancreas

“PIPDA”

Celiac plexus

SMAganglion

Posterior inferior pancreaticoduodenal artery

4 Pathways of Perineural Invasion

PLX-1: Posterior to portal vein

Posterior to panc head and PV Celiac plexus

PLX-2: Jejunal Trunk to SMA ganglion

• Posterior to pancreas, left side of uncinate• PIPDA/Jejunal trunk = conduit

• Most common route of spread (74-90%)

Anterior

• Anteriorly along GDA to CHA plexus

Inferior

• Inferiorly into root of mesentery

Celiac

plexus

SMA

ganglion

AJR:194, March 2010

Celiac plexus in situ

• Thin, disc-like structures, <5 mm thick

• Located anterior to aorta and diaphragmatic crura, medial to adrenals

• Surround celiac trunk and root of SMA

• Thin, disc-like structures, <5 mm thick

• Located between IVC and diaphragmatic crus

Right celiac ganglion

IVC

IVC

Right celiac ganglion

Right Celiac plexus on CT

Zuo et. Al, World J Radiol 2012 February 28; 4(2): 36-43

Left Celiac plexus on CT

Panc head

Left celiac ganglion

L adrenal

• Thin, disc-like structure, <5 mm thick

• Located anterior to aorta and diaphragmatic crura, medial to adrenals

• Surround celiac trunk and root of SMA

Left celiac ganglion

L adrenal

Zuo et. Al, World J Radiol 2012 February 28; 4(2): 36-43

Perineural Plexus InvasionPosterior Pathway “PLX-1” (celiac plexus)

T

T

Coronal PNI difficult to identify

PD

Axial Posterior PNI more easily visible

Perineural Plexus LandmarksPosterior PLX-2

Normal PIPDA & Jejunal Trunk

PIPDA

JT

T

Jejunal Trunk

Perineural Plexus LandmarksPNI at Posterior PLX-2

T

PIPDA

2D thin axial

T

PIPDA

3D VR coronal

Does PNI really affect survival?

76 pts with pancreatic adenoca, all had pre-op MDCT

All 76 patients met classical resectability criteria for Whipple

All had post-op chemo

Minimum follow-up 2 yrs

49 had perineural invasion

Slide courtesy of Dr. R. B. Jeffrey, Stanford University

PNI significantly reduces survivalP=0.010

MDCT Pancreatic Protocol

To diagnose PNI: High resolution SFOV CTA to visualize 1-2 mm vessel and adjacent soft tissue infiltration

Rapid IV injection 150 ml @ 4ml/sec

Biphasic acquisition (late arterial 45 sec and venous phase 70 sec)

@ 0.625 mm collimation

Cover liver and pancreas in both phases, pelvis in PV phase

Oral contrast: 750 ml of neutral contrast right before scanning

Positive contrast can obscure small mural or ampullary lesions

20 mg buscopan IV/IM

Synoptic Reporting

Narrative ReportResectable, Borderline Resectable, or Unresectable?

OPINION:

• 5 cm low attenuation partly enhancing ill-defined solid mass head of pancreas consistent with neoplasm.

• Compression and possible invasion of splenic vein with extensive perigastric venous collateral.

• Celiac artery branches are seen to traverse the superior aspect of the mass and in particular, the common hepatic artery.

• Associated lymphadenopathy.

UNRESECTABLE

Structured vs. Narrative ReportingBeth Israel Medical Center, 120 reports (2006-2011)

A hot topic…

“Complete, accurate, and reproducible radiology reporting of disease extent is essential”

“Decision regarding resectability status should be decided in consensus at multidisciplinary meetings”

624,000 downloads of sample template between Jan-Oct 2014

Department of General Surgery

Synoptic vs Free Form CT Reporting for Periampullary Malignancies:

Can we better select operative candidates?

Jeff Hawel1, Harry Marshall3, Mike Meschino2, Esther Lau1, Heather Emmerton-Coughlin1, Catherine Yoshy3, Daniele Wiseman3,

Amol Mujoomdar3, Roberto HernandezAlejandro1, Ken Leslie1

1 Department of Surgery, Western University, London ON Canada2 Schulich School of Medicine and Dentistry, Western University, London ON Canada3 Department of Radiology, Western University, London ON Canada

Resident Research Day - April 29th, 2016

Methods• A retrospective review of our prospectively maintained PAC

database (2007-2015) was performed.• Inclusion Criteria:

i. Non-curative Whipple resection (R1) or unresectable disease at laparotomy (locally advanced or metastatic disease)

ii. Pre-operative CT with appropriate protocol for synoptic reporting performed within 90 days of OR

• Pre-operative CT scans were blindly and retrospectively re-reported by consultant radiologists, using synoptic reporting template

• Defined as resectable, borderline, or unresectable according to the NCCN guidelines

• Compared to operative findings and the original free form reports

Synoptic Imaging Reporting for Periampullary Malignancies

Results


R1 or Unresectable/Metastatic (142)

Excluded Patients (96)Study Eligible Patients (46)

R1 Resection (14)

Locally Advanced (17)

Metastatic Disease (15)

Pre-Op Unavailable (9)

Imaging to OR > 90 days (11)

Inadequate Protocol (72)

Contraindications to CT (2)

Excluded Patients


Exclusion Criteria # Excluded Subsequent MRI

Pre-Op Images Unavailable 7 0 0%

Original Report Unavailable 2 2 100%

Original Report Synoptic 2 2 100%

Imaging to OR > 90 days 11 9 82%

Single Phase 52 18 35%

No Pelvis 19 9 47%

Concomitant Medical Issues 2 2 100%

Technically unacceptable 1 1 100%

Total 96 43 45%

Diagnostic Accuracy


Overall Resectability Analysis

Original Report

Resectable Borderline Unresectable Total

Staff Retrospective

Analysis

Resectable 5 1 0 6

Borderline 7 0 0 7

Unresectable 18 4 11 33

46

Agreement: 16/46 34.78%

London vs Periphery


Resectability Analysis (London)Original Report


Staff Retrospective Analysis

Resectable 1 1 0 2

Borderline 4 0 0 4


27

Agreement: 11/27 41%

Resectability Analysis (Periphery)Original Report



Resectable 4 0 0 4

Borderline 3 0 0 3


19

Agreement: 5/19 26%

Accuracy by NCCN Criteria


NCCN Criteria Borderline/Unresectable Accuracy

Ascites 5/12 42%

Superior Mesenteric Artery 3/12 25%

Celiac Axis 1/5 20%

Liver Metastasis 3/16 19%

Superior Mesenteric Vein 2/21 10%

Common Hepatic Artery 0/13 0%

Arterial Variant 0/5 0%

Portal Vein 0/21 0%

Peritoneal Metastasis 0/4 0%

Surgical Outcome



Surgical Outcome

R1 Resection Locally Advanced Metastatic Disease

Resectable 21% 15% 7%

Borderline 43% 38% N/A

Unresectable 36% 47% 93%

79%

Surgical Outcome



Surgical Outcome

R1 Resection Locally Advanced Metastatic Disease

Resectable 21% 15% 7%

Borderline 43% 38% N/A

Unresectable 36% 47% 93%

93%

Multi-Disciplinary Tumor Board• NCCN Guidelines 2015:

• “Decisions about diagnostic management and resectability should involve multidisciplinary consultation…”

• Less than 10% of total non-curative (R1 and unresectable at laparotomy) cases were discussed pre-operatively at MDTB at LHSC.


Discussion• Significant proportion of patients proceed to

resection without adequate imaging

• Synoptic reporting, coupled with expert radiologist review, better identifies and communicates CT findings to the surgeon


Study Conclusion• Patient selection can be improved with better

communication between surgeon and radiologist

• Formal imaging review and/or MDTB should be considered for all patients before resection


Outcomes of Retrospective Review

Establishment of Diagnostic Assessment Program (DAP)

Review of image quality to determine if repeat imaging is necessary

• We should work to eliminate this step

• Consistency of protocol is ideal

Double read CT Pancreas cases prior to issuing a report

Routine use of synoptic report for potential surgical cases

Final review at MCC for all cases unless clearly unresectable

Synoptic Report

• Used only for cases that are resectable or locally advanced– Not for clearly metastatic

tumors– Surgery not an option

• If not biopsy proven?– Must comment on surgical

criteria (vessels, CBD, ascites etc) in case lesion is malignant

– Can state histology not available

– Offer resectability status in event lesion is malignant.

Summary

Radiologists need to carefully look for features of resectability

May impact decision for surgical vs. neoadjuvant therapy

Look for perineural invasion – may be a biomarker of poor prognosis

Pancreatic adenocarcinoma – still a bad news story?

Eliminates repeat imaging and ensuing delays

Standardization of protocols

Report should contain all information needed for treatment planning

Potentially resectable cases should be discussed at MCC

Dialogue between radiology/surgery essential!

Synoptic Reporting

Documents

Diagnosis and Management of Pancreatic Carcinoma - Best ... Staging...The pancreatic head is richly innervated by autonomic nerve fibers coming from the celiac plexus (R and L celiac