2010 Oncology Service 2010 Oncology Service Annual ReportAnnual Report

Pancreas Cancer

Marshall Flam, MDEllen Malek, CTR Saint Agnes Medical Center

Cancer Registry

1303 East Herndon AvenueFresno, CA 93720559 450-3570www.samc.com

®

IntroductionIntroduction

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.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.

58%

11%

10%

1995-2009 SAMC Pancreas Cancer by Site1995-2009 SAMC Pancreas Cancer by Site N=528N=528

Overlapping,

Other, NOS 21%

Common Bile Duct

Duodenum

Pancreatic Duct

IntroductionIntroduction

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.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 Number of Expected New Pancreas Cancer Cases and Deaths, 2010, by Locationand 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

Age Specific Incidence Rates of Pancreas Cancer, Age Specific Incidence Rates of Pancreas Cancer,

in California, by Race, 1988-2008in California, by Race, 1988-2008

0

20

40

60

80

100

120

140

Age at DX

Rate/100,000

NH White rate

Black rate

Courtesy of Paul Mills, PhD, MPH

1995-2009 SAMC Pancreas Cancer1995-2009 SAMC Pancreas Cancer Age at Diagnosis by SexAge at Diagnosis by SexN=528N=528

32

57

103

215

121

0

50

100

150

200

250

<49 50-59 60-69 70-79 >80

Age at Diagnosis

Nu

mb

er o

f C

ase

s

MenWomenCombined

Observations: Stage at DiagnosisObservations: 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 Cancer1995-2009 SAMC Pancreas CancerStage at Diagnosis by 5 Year IntervalsStage at Diagnosis by 5 Year Intervals N=528N=528

12%

55%

17%

8%7%

1%

9%

49%

16%20%

4%1%

5%

52%

10%

19%

13%

2%

0%

10%

20%

30%

40%

50%

60%

0 I II III IV Unk/NAStage at Diagnosis

1995-1999 2000-2004 2005-2009N=192N=164N=172

NCDB Benchmark ComparisonNCDB Benchmark Comparison2000-2008 Pancreas Cancer2000-2008 Pancreas CancerStage at DiagnosisStage at Diagnosis

7%

19%

13%

51%

8%7%

18%

2% 1%

47%

11%

16%

0%

10%

20%

30%

40%

50%

60%

0 I II III IV Unk/NA

Stage at Diagnosis

SAMCN=316NCDBN=213,979

1995-2009 SAMC Pancreas Cancer1995-2009 SAMC Pancreas CancerStage at Diagnosis, In-Situ: a reviewStage at Diagnosis, In-Situ: a reviewN=4N=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 UltrasoundEndoscopic 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: TreatmentObservations: 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 Cancer1995-2009 SAMC Pancreas CancerFirst CourseFirst Course Treatment by 5 Year IntervalsTreatment by 5 Year IntervalsN=528N=528

33%

15%

31%

6%8%

4%2%

8% 9%

15%

3%

8%

38%

8%6%

10%

2%

27%

12%

27% 28%

None Surg Chemo Surg/ch Rad/ch Surg/rad/ch Other

1995-1999 2000-2004 2005-2009

N=192N=164N=172

NCDB Benchmark ComparisonNCDB Benchmark Comparison2000-2008 Pancreas Cancer2000-2008 Pancreas CancerFirst Course TreatmentFirst Course Treatment

27%

10%

33%

8% 7%

13%

2%

43%

9%

24%

3%

10%6% 6%

None Surg Chemo Surg/ch Rad/ch Surg/rad/ch Other

SAMC NCDBN=316 N=213,979

NCDB Benchmark ComparisonNCDB Benchmark Comparison2000-2008 Pancreas Cancer2000-2008 Pancreas CancerFirst Course Treatment by Stage First Course Treatment by Stage N=316N=316

No Treatment Surgery Chemotherapy *Combined Modalities

StageSAMC N=86

NCDB SAMC N=32

NCDB SAMC N=104

NCDB SAMC N=94

NCDB

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%

NCDB Benchmark ComparisonNCDB Benchmark Comparison2000-2008 Pancreas Cancer2000-2008 Pancreas CancerCombined Modality Treatment by StageCombined Modality Treatment by StageN=94N=94

Surgery + Chemo Rad + Chemo Surg/Rad/Chemo Other Specified

Tx

Stage SAMC N=24

NCDB SAMC N=23

NCDB SAMC N=40

NCDB SAMC N=7

NCDB

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 2004-2009 SAMC Pancreas Cancer (N=222)(N=222) Planned Neoadjuvant Treatment Planned Neoadjuvant Treatment Borderline Resectable with No Evidence of MetastasisBorderline Resectable with No Evidence of Metastasis N=8N=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: SurvivalObservations: 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 NCDB Observed Survival 1998-2002 Pancreas Cancer - All Stages1998-2002 Pancreas Cancer - All Stages

5.3% 5.2%5%3% 3%

6.4%

14%

27%

14%

30%

5.5% 4.7%

7%

11%

26%

0%

5%

10%

15%

20%

25%

30%

35%

1 YR 2YR 3YR 4YR 5YR

Years Survived

SAMC NCDB

N=58,577N=118

N=170

*SAMC

1995-2009 SAMC Pancreas Cancer1995-2009 SAMC Pancreas Cancer Survival by Specified GroupSurvival by Specified GroupN=528N=528

100%

75%

37.5%

25%

12.5% 12.5% 12.5%

62.5%55.5% 55.5% 55.5%

47.6%

38%

23.9%19.8%

15.5% 12%8% 7.3% 6.5% 5.7%

100%

62.5%62.5% 62.5%

5.7%

0%

20%

40%

60%

80%

100%

120%

1YR 14mos 18mos 2YR 30mos 3YR 4YR 58mos 5YR

Received Neoadjuvant Tx

Neuroendocrine Histology

All Other Histologies

N=8

N=512

N=16

?

Risk Factors for Pancreas Cancer Risk Factors for Pancreas Cancer (4)(4)

Risk factor Altered risk

Smoking 2-3 X

Caloric intake physical activity

obesity~2 X

Chronic pancreatitis 2 X

Family history of pancreas ca 7 X

Diabetes 2-3 X

Primary sclerosing cholangitis ?

Hereditary pancreatitis 60 X

ABO blood group and H. pylori? ?

Courtesy of Paul Mills, PhD, MPH

1995-2009 SAMC Pancreas Cancer 1995-2009 SAMC Pancreas Cancer Smoking is the only established risk factor for the disease Smoking is the only established risk factor for the disease (4).(4).

History of Tobacco Use History of Tobacco Use N=528N=528

Of the 528 pancreatic cancer patients 37% Were active or previous tobacco users

41% Never smoked

22% Unknown

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 Risk Factors for Pancreas Cancer New Onset DiabetesNew Onset Diabetes

Risk Factors for Pancreas CancerRisk Factors for Pancreas CancerGeneticsGenetics

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 CancerRisk Factors for Pancreas CancerGenetics: Personal History of CancerGenetics: 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 CancerRisk Factors for Pancreas Cancercont.cont. Personal History of Cancer 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 2004-2009 Pancreas Cancer Personal History of Multiple Primaries Personal History of Multiple Primaries Site Distribution Site Distribution N=48N=48

Uterus2

Cervix3

Thyroid3

Bone Marrow4

Lymph Nodes4

Colon5

Prostate11

Breast16

Lung2

Brain1

Stomach1Melanoma

1Bladder

1

Kidney1

Number of cases

*includes 4 cases of bilateral breast cancer

Palliative CarePalliative 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).

SummarySummary & Recommendations& 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 multi-disciplinary 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

SummarySummary & Recommendations& Recommendationscont.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.

ResourcesResources

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 Resources cont.cont.

o Gupta, S. et al. New-onset diabetes and pancreatic cancer. Clin 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; jtemel@partners.org