Pancreas Adenocarcinoma Update - PowerPoint Presentation

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Pancreas AdenocarcinomaUpdate

Steven P Heddinger MD

Mission Cancer + Blood

Pancreas Adenocarcinoma

“Approximately 56,700 people develop exocrine pancreatic cancer each year in the United States, and almost ALL are expected TO DIE from their disease.”

--

UpToDate

Introduction

Overview

a

ka “exocrine” pancreatic cancer = 85% of all pancreas neoplasms

2

nd

most common are endocrine or neuroendocrine tumors

Arise from ducts and acinar cells

Incidence 56,770 new cases 2018

5-yr survival rate = 9%

Men = women

4

th

leading cause of cancer death in US

7% of all cancer deaths

Clinical Presentation

Asthenia 86%

Weight loss 85%

Anorexia 83%

Abdominal pain 75%

Jaundice 60%

Nausea 51%

Diarrhea 44 %Steatorrhea 25%Thrombophlebitis 3%

Elevated Bilirubin

Other LFTS high

New onset IDDM

Ascites

Blood Clots

Incidental CT scan finding 7%

Diagnostic Approach

Labs: LFTs, CBC

Abdominal Ultrasound

CT Abdomen and Pelvis with IV/PO contrast

MRCP – image ducts, define obstruction

ERCP – image duct, place stent/relieve obstruction, brush

Endoscopic Ultrasound (EUS) - staging and biopsy

Percutaneous

bx

by Intervention Radiology

Staging laparoscopy if no diagnosis with above

CA 19-9

after

diagnosis made (NOT a screening test)

CT chest after diagnosis

PET scan and Brain MRI not needed

Genetics

4-20% of patients with PC have germline mutations

Genetic Predisposition Syndromes

Hereditary pancreatitis

HBOC (BRCA 1/2) 1.2% and 2-5% risk respectively

Peutz-Jeghers

syndrome

Lynch Syncrome

3.7% risk by age 70

Familial Pancreas Cancer

Inherited predisposition to PC that has a pair of first-degree relatives with PC without a known genetic syndrome

ASCO 2018: “All patients with PC should undergo a risk assessment for hereditary syndromes.” High-risk patients should be referred for genetic testing.

Staging

Location: Head 70%, body/tail 30%

Resectable

(anatomically and patient condition)

Borderline

resectable

= artery/vein involvement

Locally advanced = nodes seen on CTMetastatic (Stage IV)TNM Staging

Stage IA 39% 5-yr survival

Stage II 21% 5-yr survival

Stage III 11% 5-yr survival

Surgery Alone

High risk of metastatic disease in all PC

Even worse if: Body/tail , CA19-9 > 100, tumor >3cm

Late presentation of Pancreas cancer

20% of patients are surgically

resectable

at presentation

20% of surgically resectable

patients are cured

So 4% of patients are cured (0.2 x 0.2 = 0.04) with surgery alone

Thus, Pancreas Cancer is a SYSTEMIC disease.

Pancreas cancer should be considered metastatic at the time of diagnosis whether or not imaging reveals this or not

Surgery

Body/Tail: Distal Pancreatectomy +/- Splenectomy

Higher risk of

mets

Median survival 13 mo.

5% alive at 2

yrs

Head:

Pancreatoduodenectomy

(i.e. Whipple)

Removal of pancreas head, duodenum, 1

st

15cm of jejunum, common bile duct, gall bladder and part of stomach with multiple anastomoses

Vein reconstruction sometimes necessary

Minimum 7-10 days in the hospital

Minimum 6

wk

recovery

Complications: malnutrition, diarrhea, ileus, pain

¼ of the patients don’t make a suitable recovery

Surgery

Whipple …

Periop

mortality: 4% (not too bad)

5

yr

survival 10-25% (assumes adjuvant chemo)

Median survival 10-20 mo (assumes adjuvant chemo)“experienced surgeons” improve outcomes.

Post-op Prognosis (with chemo)

Node negative: 5yr survival 30%

Node positive: 5yr survival 10%

TNM staging best predicts survival

Adjuvant Chemo

Surgery alone inadequate

All Pancreas Adenocarcinoma is SYSTEMIC

ALL patients (Stage

I

A- III) improve survival with adjuvant chemotherapy

History: up until 2001, there was no adjuvant chemotherapy for Pancreas cancer

Gemcitabine alone

Improved QOL and median survival

Gemcitabine +

Xeloda

, new standard of care

What Have We Learned about Pancreas Cancer?

High Mortality

80%

unresectable

at presentation

Surgery is not enough. Not curative.

PC is a presumably a SYSTEMIC disease at the time of presentation

Whipple prior to chemo keeps at least ¼ patients from receiving adjuvant chemoAdjuvant chemo improves overall survival, but may be difficult to administer post-surgery

Surgery + Chemotherapy +/- Radiation are necessary for a potential cure/long term survival

Questions Generated

Can Surgery be improved? … probably not (been there/done that)

Can Chemo be improved? … probably YES

D

rugs

Doses

Timing (

adj vs. neo-adj)

Does Radiation Therapy improve outcomes?

Sequencing? How do we get the best/most chemo and the best surgery and possible radiation all in and in what order.

Neo-Adjuvant Chemotherapy

Neo-adjuvant means “pre-operative”

Convert a borderline or locally advanced to

resectable

Radiographic responses seen in

metatstatic

patients treated with FOLFIRINOX and Gemcitabine-

Abraxane

Goal of surgery is an R0 resection (fully resected,

neg

margins)

Gives the opportunity to get all the necessary chemotherapy in

Identifies the patients who would not benefit from surgery by giving chemo first and seeing who develops

metasteses

Neo-adjuvant Therapy

Meta-analysis of 38 studies

Neo-

adj

chemo + Surgery vs. Surgery +

adj

chemo

Overall survival 19 mo vs. 15 mo

OS in the R0 group 26

mo

vs. 15

mo

Prospective trials of “borderline”

resectable

receiving FOLFIRINOX -> Radiation/Chemo -> Surgery

Median OS 38mo (>3

yrs

!! WOW!!)

Radiation improves outcomes in the “borderline” group and the “locally advanced” group

Hepatobiliary Multidisciplinary Conference at JSCC

Surgical oncology

Medical oncology

Radiation oncology

Gastroenterology

Intervention Radiology

Diagnostic Radiology

Palliative Care

Nurse Navigator

Dietician

Doctor’s office nurses

Meets Weekly

Every

pancreas cancer patient is discussed/reviewed

Summary – Pancreas Cancer

Panc

Ca remains a greatly incurable cancer

We’ve come a long way in 25 yrs.

Surgical procedure is the same. The understanding of where to use surgery has been refined.

Newer Chemotherapy much more effective

Not every

Panc Ca patient is an immediate Hospice referral Palliative Care is instrumental in

Panc

Ca patients: establish goals of care, managing side effects, support for patient and family, quality v. quantity discussions

Neo-adjuvant chemo +/- radiation followed by surgery can give 3+ years of life in the right patient