Transcript 2010 Oncology Service Annual Report

2010 Oncology Service
Annual Report
Pancreas Cancer
Marshall Flam, MD
®
Ellen Malek, CTR
Saint Agnes Medical Center
Cancer Registry
1303 East Herndon Avenue
Fresno, CA 93720
559 450-3570
www.samc.com
Introduction

The Pancreas is a small spongy organ
which lies just under the curvature of the
stomach and deep within the abdomen.

The function of the pancreas is complicated
but to simplify, it does primarily two things.

It produces enzymes which are useful in the
digestion of food. This function culminates
in the exocrine portion of the pancreas.

Secondly, it secretes hormones from the
endocrine portion of the pancreas which,
among other things, helps maintain and
regulate blood sugar levels.
cont.

Up to 95% of pancreas cancers arise from the
exocrine portion of the organ.

During 1995-2009, exocrine tumors
accounted for 97% of the pancreatic cancers
accessioned into the Saint Agnes Cancer
Registry (1). For the purposes of this study two cases
of lymphoma of the pancreas were excluded.

Most of the exocrine tumors (90%) are from
ductal cells those which line the pancreatic
ducts and are classified as carcinomas. The
least common exocrine cancer comes from
acinar cells.

About three quarters of exocrine tumors of
the pancreas arise in the head of the pancreas.

Some arise in the body of the organ and less
than ten percent arise in the tail of the
pancreas.
1995-2009 SAMC Pancreas Cancer by Site
N=528
Common
Bile Duct
Pancreatic Duct
Duodenum
10%
11%
58%
Overlapping,
Other, NOS
21%
Introduction

Cancers of the endocrine portion of the pancreas,
as noted, are less common that exocrine cancer.

They are typically referred to as neuroendocrine
(or islet-cell) tumors, arising from the hormone
producing area of the organ.

Between 1995-2009 there were only 16 cases of
neuroendocrine carcinoma diagnosed and/or
treated at the medical center.

Endocrine tumors have a different natural history.
They tend to be slower growing and have a better
prognosis. Treatment of neuroendocrine tumors is
distinct from that of adenocarcinomas of the
pancreas.

National Cancer Data Base data which is utilized
for comparison analysis includes neuroendocrine
cancer in case selection criteria for Pancreas (5/6);
therefore, the 16 cases of neuroendocrine cancer
are included in all study data unless specified.
cont.

Each year more than 30,000 people in the US are
diagnosed with adenocarcinoma of the pancreas (2).

Most will die by the end of one year.

In 2010, pancreas cancer was the twelfth most
common cancer diagnosed in Fresno County (4).

The incidence of pancreatic cancer increases with
age, most being diagnosed between age 60 and 80.
However, age specific incidence rates of pancreas
cancer in California between 1988 and 2008 reflect
rates rising at age 55. This observation appeared to
be more pronounced for African Americans (4).

Over the study period 1995-2009 there were 528
cases of pancreatic cancer diagnosed and/or
treated at SAMC. There were 251 men and 277
women. The median age at diagnosis was 73.
Race/ethnicity breakdown noted Non-Hispanic
Whites accounted for 78%, 14% Hispanic, 4%
Asian, 3% African American and 1%
Other/Unknown.
Number of Expected New Pancreas Cancer Cases
and Deaths, 2010, by Location
Location
New
Deaths
SAMC *2009 data
40
31
Fresno Co.
80
65
California
3,881
3,543
US
42,470
35,240
World
277,000
266,000
Courtesy of Paul Mills, PhD, MPH
00
01 yea
r
-0
4 s
y
05 e a
-0 rs
9
y
10 e a
-1 rs
4
1 5 ye a
-1 rs
9
y
20 e a
-2 rs
4
2 5 ye a
-2 rs
9
3 0 ye a
-3 rs
4
y
35 e a
-3 rs
9
4 0 ye a
-4 rs
4
4 5 ye a
-4 rs
9
y
50 e a
-5 rs
4
5 5 ye a
-5 rs
9
6 0 ye a
-6 rs
4
y
65 e a
-6 rs
9
7 0 ye a
-7 rs
4
y
75 e a
-7 rs
9
8 0 ye a
-8 rs
4
ye
85 ars
+
ye
ar
s
Age Specific Incidence Rates of Pancreas Cancer,
in California, by Race, 1988-2008
140
120
100
80
Rate/100,000
60
NH White rate
40
Black rate
20
0
Age at DX
Courtesy of Paul Mills, PhD, MPH
1995-2009 SAMC Pancreas Cancer
Age at Diagnosis by Sex
N=528
Men
Women
Combined
250
215
Number of Cases
200
150
121
103
100
57
50
32
0
<49
50-59
60-69
Age at Diagnosis
70-79
>80
Observations: Stage at Diagnosis

Stage at Diagnosis displayed in five year
intervals between 1995-2009 indicated that
although Saint Agnes showed marginal gains
in detecting pancreatic cancers at earlier stages,
the majority of patients were still Stage IV at
the time of their diagnosis.

For the years 2000-2008 SAMC had a higher
percentage of Stage II and Stage III pancreatic
cancer when compared to National Cancer
Data Base statistics despite the lack of
endoscopic ultrasound for staging. Saint Agnes
also had a similar percentage of Stage IV, 51%
compared to 47% seen in the national data.

From the Cancer Registry perspective, the declining
percentages of Unknown/NA stage observed in both
SAMC five year interval data and national
comparison data, reflect the Cancer Program’s
increased emphasis on the importance of accurate
staging and demonstrates improvement in assignment
and capturing of stage allowing better stratification of
data for analysis.
1995-2009 SAMC Pancreas Cancer
Stage at Diagnosis by 5 Year Intervals
N=528
1995-1999
2000-2004
2005-2009
N=172
N=164
N=192
60%
55%
52%
49%
50%
40%
30%
20% 19%
20%
13%
7%
10%
8%
1% 1% 2%
4%
0
I
17% 16%
12%
9%
10%
5%
0%
II
III
Stage at Diagnosis
IV
Unk/NA
NCDB Benchmark Comparison
2000-2008 Pancreas Cancer
Stage at Diagnosis
SAMC
N=316
NCDB
N=213,979
60%
51%
50%
47%
40%
30%
19%
20%
16%
18%
13%
11%
8%
7% 7%
10%
2% 1%
0%
0
I
II
III
Stage at Diagnosis
IV
Unk/NA
1995-2009 SAMC Pancreas Cancer
Stage at Diagnosis, In-Situ: a review
N=4





Between 1995-2009 there were 5 cases of carcinoma in-situ of the
pancreas. One case of an elderly person, did not undergo complete staging
evaluation; therefore, the case was not included for review.
Ages ranged from 57-78 years old. Two men and two women.
There was one case of invasive carcinoma of the head of the pancreas with
simultaneous second primary adenocarcinoma in-situ of the pancreatic
duct. The patient underwent Whipple resection followed by chemotherapy
for the invasive tumor. Surviving 15 months and noted to be free of
disease at that time.
One case, in-situ mucinous malignant tumor of the head of the pancreas
with a simultaneous diagnosis of a bladder cancer. Survival of 9 years,
tumor status was unknown.
The 2 remaining in-situ cases noted recurrent/chronic pancreatitis with
complaints of abdominal pain. One case had an obstructive lesion and
found to have multiple foci of adenocarcinoma involving the pancreatic
duct branches. CA 19-9 was elevated. Survival of 6 years with no
evidence of disease. The other case of chronic pancreatitis noted
abdominal pain. CA 19-9 was normal. He was found to have a papillary
mucinous neoplasm involving the head of the pancreas. Noted to be alive
at 27 months.
Endoscopic Ultrasound

2009 SAMC Pancreas Cancer cases were reviewed to
determine the utilization of endoscopic ultrasound
(EUS) as part of the diagnostic evaluation.
Of the 40 cases, 3 patients had EUS recommended;
only 2 patients underwent the study.
•
The role of endoscopic ultrasound (EUS) in staging is
becoming increasingly important . EUS is considered
complimentary to CT, providing additional information for
patients whose CT scans show no lesion or who have
questionable involvement of blood vessels or lymph nodes.
•
EUS can be used to evaluate periampullary masses
separating invasive from non-invasive lesions.
•
EUS directed FNA biopsy is preferable to CT guided FNA in
cases of resectable disease because of the much lower risk of
peritoneal seeding as compared with the percutaneous
approach.
•
EUS has a promising role in screening high risk patients.
Observations: Treatment

1995-2009 SAMC First Course Treatment
data by five year intervals indicated that
fewer patients received no treatment and less
underwent surgery alone, while the use of
chemotherapy increased given either alone or in
combination over the study period.

2000-2008 National Cancer Data Base
comparison of First Course Treatment included
data from 1394 hospitals comprising 213,979
cases. Saint Agnes encompassed 316 cases
(inclusive of 8 neuroendocrine cancers). When
compared to the national data, Saint Agnes
Medical Center cancer specialist’s preference
for treatment was again clearly reflected.
Although, there were similar percentage for
surgery alone, there was greater use of
chemotherapy, given alone and in combination,
notably chemotherapy, radiation and surgery.

NCDB comparison 2000-2008 First Course
Treatment by Stage and the breakout of
Combined Modality Treatment by Stage is
provided (see graphs).
1995-2009 SAMC Pancreas Cancer
First Course Treatment by 5 Year Intervals
N=528
1995-1999
2000-2004
2005-2009
N=172
N=164
N=192
38%
33%
31%
27% 28%
27%
15%
15%
12%
10%
8%
6%
8% 8%
8% 9%
6%
4%
None
Surg
Chemo
Surg/ch
Rad/ch
Surg/rad/ch
2% 3% 2%
Other
NCDB Benchmark Comparison
2000-2008 Pancreas Cancer
First Course Treatment
SAMC
NCDB
N=316
N=213,979
43%
33%
27%
24%
13%
10% 9%
10%
8%
7%
6%
3%
None
Surg
Chemo
Surg/ch
6%
2%
Rad/ch
Surg/rad/ch
Other
NCDB Benchmark Comparison
2000-2008 Pancreas Cancer
First Course Treatment by Stage
N=316
No Treatment
NCDB
Surgery
NCDB
SAMC
0
2%
0.2%
9%
4%
0%
0.1%
0%
0.1%
I
12%
6%
6%
20%
5%
2%
6%
9%
II
6%
9%
28%
38%
5%
5%
44%
32%
III
2%
7%
28%
12%
4%
7%
29%
22%
IV
60%
52%
25%
10%
81%
74%
19%
25%
Unk/NA
17%
26%
3%
15%
6%
12%
2%
0.09%
Overall
27%
43%
10%
9%
33%
24%
30%
25%
N=32
SAMC
NCDB
*Combined
Modalities
SAMC NCDB
Stage
N=86
SAMC
Chemotherapy
N=104
N=94
NCDB Benchmark Comparison
2000-2008 Pancreas Cancer
Combined Modality Treatment by Stage
N=94
Stage
Surgery +
Other Specified
Rad + Chemo
Surg/Rad/Chemo
Chemo
Tx
SAMC NCDB SAMC NCDB SAMC NCDB SAMC NCDB
N=24
N=23
N=40
N=7
0
0%
0.2%
0%
0.1%
0%
0.1%
0%
0.4%
I
0%
10%
8%
8%
10%
13%
0%
8%
II
58%
52%
26%
18%
48%
56%
29%
18%
III
25%
9%
30%
31%
33%
20%
14%
14%
IV
17%
19%
30%
31%
8%
6%
57%
39%
Unk/NA
0%
9%
4%
12%
3%
4%
0%
21%
Overall
8%
3%
7%
10%
13%
6%
2%
6%
2004-2009 SAMC Pancreas Cancer (N=222)
Planned Neoadjuvant Treatment
Borderline Resectable with No Evidence of Metastasis N=8

Over the six year period, eight patients received neoadjuvant chemotherapy
and radiation therapy at Saint Agnes.

Ages ranged from 43 to 82. Stage at diagnosis included Stage IB to Stage III.
Clinical tumor size varied between 1.8cm to 6.6cm.

There were (5) T4, (1) T3 and (2) T2; one of these cases was N1.

Three patients did not undergo surgical resection. One of which experienced
progression of disease while on treatment.

Five patients had Whipple procedures. Of these, (2) had no residual tumor,
(1) had significant tumor reduction and (2) had unknown pathologic tumor size
having had their surgery performed elsewhere.

All eight patients achieved minimum survival of 14 months.

Four were never free of disease, 1 experienced a local recurrence at 4 months
and 3 were free of disease.

At the time of this study, 4 were alive and 4 have expired.

Of those living, survival included (2) at 19 months, (1) at 30 months and…

One patient age 48 and Clinical Stage T4N1M0, III at the time of diagnosis
is 4 years and 10 months status post treatment.
Observations: Survival

National Cancer Data Base comparison data for
the years 1998-2002 was utilized to analyze
survival. Direct comparison per NCDB criteria was
made which, excludes cases of multiple primary cancers
and unknown stage at diagnosis (5).



A comparison of all SAMC cases for the given
years regardless of history of other malignancies
was also provided (displayed in green).
Of those patients with pancreas cancer diagnosed
and/or treated at Saint Agnes Medical Center
between 1998-2002, per NCDB criteria N=118,
survival at one and two years was superior to
that observed in the national data. Survival at
three, four and five years was noted to be
marginally less than for NCDB.
When all SAMC cases of pancreas cancer, N=170,
were included in the analysis, regardless of the
patient’s history of other primaries, survival at
one and two years remained superior to national
outcomes and, comparable survival outcomes
were noted at three, four and five years.
NCDB Observed Survival
1998-2002 Pancreas Cancer - All Stages
SAMC
NCDB
N=118
N=58,577
35%
*SAMC
30%
30%
27%
N=170
26%
25%
20%
14% 14%
15%
11%
10%
7%
6.4%
5%
5%
5.5%
5.3%
5.2%
4.7%
3%
3%
4YR
5YR
0%
1 YR
2YR
3YR
Years Survived
1995-2009 SAMC Pancreas Cancer
Survival by Specified Group
N=528
Received Neoadjuvant Tx
N=8
Neuroendocrine Histology
N=16
120%
100%
All Other Histologies
N=512
100%
100%
75%
80%
62.5%
62.5%
62.5%
62.5%
55.5%
60%
55.5%
55.5%
47.6%
38%
37.5%
40%
23.9%
20%
25%
19.8%
15.5%
12%
8%
12.5%
12.5%
7.3%
12.5%
6.5%
5.7%
0%
1YR
14mos
18mos
2YR
30mos
3YR
4YR
58mos
?
5.7%
5YR
Risk Factors for Pancreas Cancer (4)
Risk factor
Smoking
Caloric intake
Altered risk
2-3 X
physical activity
obesity
~2 X
Chronic pancreatitis
2X
Family history of pancreas ca
7X
Diabetes
Primary sclerosing cholangitis
Hereditary pancreatitis
ABO blood group and H. pylori?
2-3 X
?
60 X
?
Courtesy of Paul Mills, PhD, MPH
1995-2009 SAMC Pancreas Cancer
Smoking is the only established risk factor for the disease (4).
History of Tobacco Use
N=528

Of the 528 pancreatic cancer patients
37% Were active or previous tobacco users

41% Never smoked

22% Unknown
Risk Factors for Pancreas Cancer
New Onset Diabetes

Numerous studies have shown association
between new onset diabetes and the development
of pancreatic cancer (6).

2009 SAMC Pancreas Cancer cases were
reviewed to determine the incidence of new
onset diabetes. Of the 40 cases, 52.5% (21) did
not have a diagnosis of diabetes recorded in the
medical record. 47.5% (19) did indicate a
diagnosis of diabetes. Of these,
• 4 were diagnosed within the past six months
• 4 had diabetes for 3 years or longer
• 11 had a diagnosis of diabetes with no
specific information on the duration
Risk Factors for Pancreas Cancer
Genetics


Genetic predisposition is present in 5%-10% of patients (6), and
familial excess of pancreatic cancer is associated with high risk.
Known/suspected association between etiologically related cancers
include melanoma (implicating p16), breast/ovarian cancer
(BRCA1-2) and Lynch syndrome spectrum cancers, e.g. uterine
and colorectal cancers (MLH1, MSH2, MSH6, PMS2).
Between 2004-2009 there were 222 cases of pancreatic cancer
involving 221 patients, noting one case with two primaries of the
pancreas. Of these patients, 45.2% (100) had no family history of
cancer, 38.4% (85) indicated a family history of cancer and 16.2%
(36) had unknown or missing information.
Of the 85 patients with a family history of cancer,
5.4% (12) had a family history of pancreatic cancer in a 1st
and/or 2nd degree relative. No gender bias or effect on stage at
diagnosis was identified for this group.
36% (79) noted a family history of cancer, nos (not pancreas)
involving a 1st and/or 2nd degree relative.
Risk Factors for Pancreas Cancer
Genetics: Personal History of Cancer
Further analysis of the 221 pancreatic cancer
patients identified between 2004-2009 noted, 22%
(48) had a personal history of at least one other
primary cancer: 36 patients had two primaries,
10 had three and 2 noted four primaries.
Most common additional primary sites included
Breast, Prostate, Colon. Additional observations
included,
Four women with bilateral postmenopausal breast
cancer. The predominant histology was ductal
carcinoma. Each had adenocarcinoma of the head of
the pancreas or overlapping site of origin. One of
these patients had two 1st degree relatives with
pancreatic cancer as well as one 1st degree relative
with uterine cancer. All but one patient has expired.
.
Risk Factors for Pancreas Cancer
cont. Personal History of Cancer
One patient noted her first cancer at age 25,
a uterine cancer, followed by the diagnosis of
pancreatic cancer at age 49, with simultaneous
diagnosis of metastatic breast cancer. Her family
history noted a total of five 1st and 2nd degree
relatives with cancer, nos (not pancreas). This patient
has expired.
Of the three thyroid cancer cases observed,
1) First of three primaries diagnosed at age 64, thyroid
cancer followed by bone marrow malignancy at 78 and
neuroendocrine carcinoma of the tail of the pancreas
at age 80. She had no family history of cancer.
2) Also first of three primaries, uterine cancer at age 56
followed by thyroid cancer at age 61, and at age 86
tail of the pancreas cancer, nos. Her family history was
unknown.
3) Two primaries, adenocarcinoma of the thyroid
diagnosed at age 75 followed an adenocarcinoma of the
body of the pancreas at age 83. Her family history was
unknown.
2004-2009 Pancreas Cancer
Personal History of Multiple Primaries
Site Distribution
N=48
Melanoma
1
Lung
2
Stomach
1
Bladder
1
Kidney
1
Brain
1
Breast
16 *includes
Uterus
2
4 cases of
bilateral breast cancer
Cervix
3
Number of cases
Thyroid
3
Bone Marrow
4
Lymph Nodes
4
Prostate
11
Colon
5
Palliative Care

The goal of Palliative Care for the patient with
pancreatic cancer is to prevent and relieve suffering
and to support the best possible quality of life for
patients and their families, regardless of the stage
of the disease or the need for other therapies.

Palliative Care can be delivered concurrently with
other cancer treatments or as the main focus of care.

Effective Palliative Care supports clear, consistent, and
empathetic communication with patient and family
about the natural history of their cancer and the
patient’s prognosis.

Palliative Care upholds patient and family centered
care that focuses upon effective management of pain
and other distressing symptoms, while incorporating
psychosocial and spiritual care according to
patient/family needs, values, beliefs and culture(s).

Some studies have shown when Palliative Care is
provided by a team of experts early in the course of
treatment it not only improves quality of life but
also prolongs survival (7).
Summary & Recommendations


Pancreas cancer kills about 35,000 Americans each year and five year survival
remains poor (~5%), making pancreas cancer the fourth leading cause of cancer
death in the US for both men and women (1). Neither incidence nor mortality
rates appear to be changing over time (4).
‘All patients diagnosed with pancreatic cancer should be evaluated by a multidisciplinary team of cancer specialists including Surgery, Medical Oncology,
Radiation Oncology and, Palliative Care if needed.’
‘Physicians need to separate out neuroendocrine cancers from the more
common types of pancreatic cancer because their prognosis, natural history
and treatment are very different.’
‘Endoscopic ultrasound (EUS) can improve our ability to accurately stage
pancreatic cancer and aid in determining the most effective treatment.’
‘Patients age 40 and older diagnosed with a sudden onset of type II diabetes,
should be assessed for pancreatic cancer annually.’
Preoperative chemotherapy or chemoirradiation in patients with marginally
non-resectable disease does not appear to be clearly disadvantageous and ‘more
patients with pancreatic cancer may benefit if chemotherapy and radiation
therapy is given preoperatively’, because prolonged recovery after
pancreaticoduodenectomy prevents the delivery of postoperative therapy in up to
25% of eligible patients (6).
‘While overall survival has not yet increased, selective individuals treated
aggressively with multi-modality treatment do experience long term survival.’
Marshall Flam, MD, Hematology-Oncology Medical Group of Fresno
Summary & Recommendations
cont.

Hereditary factors play an role in the etiology of
pancreatic cancer (up to 10% of cases). ‘Families with
multiple cases of pancreatic cancer should be offered
genetic consultation/testing for hereditary
breast/ovarian cancer (BRCA 1-2), which is the
primary genetic association. Prevention/early
detection is the goal.’ - C. Dawn DeLozier, PhD,
Medical Geneticist & Genetic Counselor, Saint Agnes
Cancer Center.

‘Palliative Care referral should be considered with
the initial diagnosis of pancreatic cancer. Early
consultation/collaboration with an expert Palliative
Care Team may improve quality of life and survival.’
- Michael Nisco, MD, Medical Director Palliative
Care Program, Saint Agnes Medical Center.
Resources
1.
SAMC Cancer Registry database; www.samc.com
*Comment: This report is developed from our hospital based registry
experience which is not ‘population based’ data.
2.
SEER 2002 estimate; www.seer.cancer.gov
3.
Cancer Facts & Figures; www.cancer.org/statistics
4.
‘Pancreas Cancer: An Epidemiologic Perspective’,
Paul K. Mills, Ph.D. MPH, Department of Internal
Medicine, UCSF Fresno, Cancer Registry of Central California;
www.ccral.org
*IARC Statement, (2004) “Cancer of the pancreas is causally associated
with cigarette smoking. The risk increases with duration of smoking and
number of cigarettes smoked daily. The risk remains elevated after allowing
for potentially confounding factors such as alcohol consumption. The relative
risk decreased with increasing time since quitting smoking”
5.
National Cancer Data Base, Benchmark Comparison
Reports and Survival Reports; www.facs.org
6.
National Comprehensive Cancer Network (NCCN)
Guidelines in Oncology; www.nccn.org
*NCCN Guidelines note that the TNM staging system provides reasonable
stage discrimination for the inclusion of neuroendocrine tumors..
Resources
cont.
o
Gupta, S. et al. New-onset diabetes and pancreatic cancer.
Gastroenterol Hepatol 2006; 1366-1372.
o
Chari ST, Leibson CL, Rabe KG, et al. Probability of
pancreatic
cancer following diabetes: a population-based study. Gastroenterology 2005;
129:504-511.
o
Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy
for adenocarcinoma of the pancreas: treatment variables and survival
duration. Ann Surg Oncol 2001;8:123-132.
o
Lynch HT, Smyrk T, Kern SE, et al. Familial pancreatic cancer: a review.
Semin Oncol 1996;23:251-275.
o
Wang W, Chen S, Brune KA, et al. PancPRO: Risk assessment for individuals
with a family history of pancreatic cancer. J Clin Oncol 2007;25:1417-1422.
7.
‘Early Palliative Care for Patients with Metastatic
Non-Small Cell Lung Cancer’, Jennifer Temel, MD,
et al. New England Journal of Medicine, 2010; 363:733-42;
[email protected]
Clin