1 . The median age at diagnosis of pancreatic cancer is
| A) | | 20 years. |
| B) | | 40 years. |
| C) | | 55 years. |
| D) | | 70 years. |
During 2021 in the United States, an estimated 60,430 people
will be diagnosed with pancreatic cancer, which represents 3.2% of all new cancer cases and
the 11th most common new cancer diagnosis. The median age at diagnosis is 70 years [18].
2 . Which of the following statements regarding diet and pancreatic cancer risk is FALSE?
| A) | | High plasma 25-hydroxyvitamin D levels increase the risk for pancreatic cancer. |
| B) | | Pancreatic cancer incidence may be lower in persons with higher intake of fresh fruits. |
| C) | | Pancreatic cancer incidence may be lower in persons with higher intake of vegetables rich in folate and lycopenes. |
| D) | | There is some evidence that higher consumption of red/processed meat is associated with elevation in pancreatic cancer risk. |
There is some evidence that higher consumption of
red/processed meat is associated with elevation in pancreatic cancer risk, but other
studies have failed to identify dietary risk factors for PDAC [11]. Pancreatic cancer incidence may be lower
in persons with higher intake of fresh fruits and vegetables rich in folate and lycopenes
(e.g., tomatoes) [30].
A link between vitamin D and risk for pancreatic cancer
is inconsistent, but some data suggest low plasma 25-hydroxyvitamin D levels may increase
the risk for pancreatic cancer, especially in those with low retinol/vitamin A intake
[31]. Coffee and tea consumption are not
associated with pancreatic cancer risk, despite early reports to the contrary [24].
3 . Starting at 30 months prediagnosis, pancreatic ductal adenocarcinoma (PDAC) showed three distinct metabolic phases. Which of the following is NOT one of these phases?
| A) | | Cachexia |
| B) | | Pancreatitis |
| C) | | Pre-cachexia |
| D) | | Hyperglycemia |
Numerous studies have identified new-onset diabetes,
weight loss, and soft tissue changes in patients with PDAC at diagnosis, but their
inter-relationship and connection to PDAC remained unaddressed. From 2000 through 2015,
temporal changes in the five years preceding PDAC diagnosis of 219 patients diagnosed with
PDAC were compared to 657 controls [46].
From 60 to 30 months before PDAC diagnosis, patients did not significantly differ from
controls. However, starting at 30 months prediagnosis, PDAC showed three distinct
metabolic phases, each marked by onset and significant progressive worsening of one or
more metabolic abnormalities [46]:
Phase 1, hyperglycemia (30 to 18 months before PDAC diagnosis): A significant
proportion of patients develop hyperglycemia, without soft tissue changes.
Phase 2, pre-cachexia (18 to 6 months before PDAC diagnosis): Decreases in serum
lipids, weight loss, and the first soft tissue change (subcutaneous abdominal tissue
loss) are seen. A profile appears of advanced prediabetes (i.e., fasting blood
glucose 120–126 mg/dL or A1c of 6% to 6.5%). In type 2 diabetes, this is associated
with weight gain and hyperlipidemia due to insulin resistance. In PDAC, decreases in
weight and serum lipids despite rising glucose levels are paradoxical.
Phase 3, cachexia (less than 6 months before PDAC diagnosis): Onset of muscle
loss, visceral adipose tissue loss, and decreasing high-density lipoprotein.
Continued decreases in all other serum lipids, subcutaneous abdominal tissue, and
weight. Fasting blood glucose continues rising.
4 . The most common precancerous precursor lesions associated with pancreatic cancer are
| A) | | mucinous cystic neoplasms (MCN). |
| B) | | cervical intraepithelial neoplasia (CIN). |
| C) | | pancreatic intraepithelial neoplasia (PanIN). |
| D) | | intraductal papillary mucinous neoplasm (IPMN). |
Through pathways and somatic mutations that differ modestly
in each lesion, PDAC develops from precancerous precursor lesions: pancreatic
intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and
mucinous cystic neoplasms (MCNs). The most common are PanINs (approximately 90%), and the
least common are MCNs. However, all precursor lesions have key similarities [4,48,50]:
Early oncogene mutations initiate tumorigenesis.
Later loss of tumor suppressor genes drive tumor progression, high-grade
dysplasia, and invasive cancer.
Increasing grades of dysplasia are associated with accumulation of somatic
mutations in key driver genes.
5 . Which of the following statements regarding pancreatic cancer screening is TRUE?
| A) | | Hereditary pancreatitis is a clear indication for annual pancreatic cancer screening and surveillance. |
| B) | | Population screening to achieve earlier detection and intervention of PDAC is federal policy in the United States. |
| C) | | The U.S. Preventive Services Task Force recommends against screening for pancreatic cancer in asymptomatic adults. |
| D) | | The International Cancer of the Pancreas Screening (CAPS) Consortium recommends pancreatic surveillance for all adults to detect and resect early pancreatic cancer and its high-grade precursors. |
PANCREATIC CANCER SCREENING
With the low population incidence of PDAC (lifetime risk:
1.3%), absence of biomarker screening targets, and high cost of sensitive imaging methods, the
U.S. Preventive Services Task Force recommended against screening for pancreatic cancer in
asymptomatic adults in 2019, reaffirming its previous conclusion in 2004 [74]. As population screening to achieve earlier
detection and intervention of PDAC is not currently feasible, other approaches for this
objective have been identified.
In Australia, public awareness campaigns have highlighted the
often vague symptoms of PDAC and encouraged individuals to seek medical attention early.
Underscoring this point, one study found that many people who were ultimately diagnosed with
PDAC were falsely reassured by the subtle, intermittent nature of their symptoms over the
preceding months [75,76].
As a relatively rare cancer, many primary care providers will
only see a PDAC case every few years, making it imperative to elevate awareness of early PDAC
signs and symptoms among these professionals. A retrospective case-control study in primary
care found that patients sought medical attention 18 times on average in the period preceding
their pancreatic cancer diagnosis. PDAC was associated with 11 alarm symptoms; back pain,
lethargy, and new-onset diabetes were unique features of PDAC [75,77].
6 . Most pancreatic cancers (approximately 75%) originate in the
| A) | | liver. |
| B) | | tail of the pancreas. |
| C) | | body of the pancreas. |
| D) | | head of the pancreas. |
CLINICAL EVALUATION OF PANCREATIC CANCER
Most pancreatic cancers (approximately 75%) originate in the
head of the pancreas and typically metastasize to regional lymph nodes first, then to the
liver. PDAC can also directly invade surrounding visceral organs (e.g., duodenum, stomach,
colon); metastasize to any surface in the abdominal cavity via peritoneal spread where
development of ascites carries an ominous prognosis; or spread to the skin as painful nodular
metastases. By the time of diagnosis, 85% to 90% of patients have locally advanced tumors that
have involved retroperitoneal structures, spread to regional lymph nodes, or metastasized to
the liver or lung [2,13,24,81].
7 . Which of the following should trigger inclusion of PDAC in the differential diagnosis?
| A) | | Ongoing hypoglycemia with significant weight gain |
| B) | | The constellation of abdominal pain, hyperkalemia, and weight loss |
| C) | | Longstanding hyperglycemia regardless of other symptoms or diagnoses |
| D) | | Development of abdominal pain, jaundice, or weight loss in the context of newly diagnosed diabetes, family history of PDAC, or history of pancreatitis |
CLINICAL EVALUATION OF PANCREATIC CANCER
Development of abdominal pain, jaundice, or weight loss in
the context of newly diagnosed diabetes, family history of PDAC, or history of pancreatitis
should trigger inclusion of PDAC in the differential diagnosis [2]. Furthermore, past three-year onset of
diabetes or ongoing hyperglycemia with significant weight loss and decreasing serum lipids
should be considered a potential PDAC, even if abdominal pain or jaundice are absent, with
urgent referral a priority.
8 . Referral for genetic counseling should be considered for patients diagnosed with pancreatic cancer, especially those
| A) | | of Ashkenazi Jewish ancestry. |
| B) | | with a family history of cancer or who are young. |
| C) | | for whom a hereditary cancer syndrome is suspect. |
| D) | | All of the above |
CLINICAL EVALUATION OF PANCREATIC CANCER
Referral for genetic counseling should be considered for
patients diagnosed with pancreatic cancer, especially those with a family history of cancer
or who are young, those of Ashkenazi Jewish ancestry, or for whom a hereditary cancer
syndrome is suspect. A free pancreatic cancer risk prediction tool, PancPRO, is available
and may help determine risk [11].
9 . Which of the following is the most common sign/symptom in patients with pancreatic cancer?
| A) | | Jaundice |
| B) | | Polydipsia |
| C) | | Abdominal pain |
| D) | | Significant weight gain |
CLINICAL EVALUATION OF PANCREATIC CANCER
Abdominal pain is the most common symptom, usually
insidious in onset and often present for one to two months at the time of presentation,
the pain is often severe, and unrelenting in nature. The typical gnawing, visceral quality
of pain is generally epigastric, radiating to the sides and/or straight through to the
back; some patients may describe the pain as originating in the back. Nighttime pain is
often the predominant complaint. Some patients note increased pain after eating and
worsened pain when lying flat [24,81]. Rarely, acute pain develops when an
episode of acute pancreatitis results in tumor occlusion of the main pancreatic duct [84].
10 . Which of the following is a common site of metastases in patients with advanced pancreatic cancer?
| A) | | Liver |
| B) | | Brain |
| C) | | Colon |
| D) | | Bladder |
CLINICAL EVALUATION OF PANCREATIC CANCER
Metastatic disease most commonly affects the liver,
peritoneum, lungs, and less frequently, bone [24,84]. Patients presenting
with or developing advanced intra-abdominal disease may have ascites, a palpable abdominal
mass, hepatomegaly from liver metastases, or splenomegaly from portal vein obstruction.
Subcutaneous metastases (termed Sister Mary Joseph nodules) in the paraumbilical area
signify advanced disease; pancreatic cancer is the origin of a cutaneous metastasis to the
umbilicus in 7% to 9% of cases [24,84]. A metastatic mass in the rectal pouch may
be palpable on rectal examination (Blumer shelf). As a metastatic node, left supraclavicular
lymphadenopathy may be palpable, while other nodes in the cervical area may also be
involved.
11 . What is the preferred imaging for initial evaluation of suspected PDAC?
| A) | | Ultrasonography |
| B) | | Endoscopic retrograde cholangiopancreatography (ERCP) |
| C) | | Multidetector computed tomography (MDCT) angiography with IV contrast |
| D) | | Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) |
THE DIAGNOSTIC AND STAGING WORKUP
Multidetector computed tomography (MDCT) angiography
with intravenous (IV) contrast is the preferred imaging for initial evaluation of
suspected PDAC. The Pancreatic CT Protocol standardizes its use, making MDCT highly
accurate for assessing tumor extent, vascular invasion, and distant metastases [11,16,88,89]. The NCCN recommends that MDCT
angiography should also cover the chest and pelvis for complete staging [11].
12 . Although unsuitable for asymptomatic screening, which biomarker is the most clinically useful in PDAC?
| A) | | Alpha-fetoprotein (AFP) |
| B) | | Carcinoembryonic antigen (CEA) |
| C) | | Carbohydrate antigen 125 (CA-125) |
| D) | | Carbohydrate antigen 19-9 (CA19-9) |
THE DIAGNOSTIC AND STAGING WORKUP
CA19-9 is a sialylated Lewis A blood group antigen,
commonly expressed and shed in benign and malignant pancreatic and biliary disease. Although
unsuitable for asymptomatic screening, CA19-9 is the most clinically useful biomarker in
PDAC, with good sensitivity (79% to 81%) and specificity (82% to 90%) in symptomatic
patients. A normal serum level is 37 U/mL [90].
13 . According to the NCCN guideline, PDAC tumors that are involved with nearby structures would be classed as
| A) | | Resectable |
| B) | | Localized and complicated |
| C) | | Metastatic (non-resectable) |
| D) | | Borderline resectable or locally advanced |
THE DIAGNOSTIC AND STAGING WORKUP
The NCCN guideline classes PDAC resectability into the
following clinical stages [11]:
Stage 1: Resectable
Stage 2: Borderline resectable (i.e., tumors that are involved with nearby
structures so as to be neither clearly resectable nor clearly unresectable with a
high chance of removal of all macroscopic disease)
Stage 3: Locally advanced (i.e., tumors that are involved with nearby structures
to an extent that renders them unresectable despite the absence of metastatic
disease)
Stage 4: Metastatic (i.e., non-resectable)
14 . A patient with pancreatic cancer who is capable of all self-care but unable to carry out any work activities would receive an Eastern Cooperative Oncology Group Performance Status (ECOG) score of
TREATMENT APPROACHES FOR PANCREATIC CANCER
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS SCALE
| Score | Definition |
|---|
| 0 |
| Fully active | | No performance restrictions |
|
| 1 |
| Strenuous physical activity restricted | | Fully ambulatory and able to carry out light work |
|
| 2 |
| Capable of all self-care but unable to carry out any work
activities | | Up and about >50% of waking hours |
|
| 3 |
| Capable of only limited self-care | | Confined to bed or chair >50% of waking hours |
|
| 4 |
| Completely disabled | | Cannot carry out any self-care | | Totally confined to bed or chair |
|
| 5 | Deceased |
15 . The conventional Whipple procedure (pancreaticoduodenectomy) is used for tumors
| A) | | growing multifocally. |
| B) | | in the pancreatic body or tail. |
| C) | | in the pancreatic head or periampullary region. |
| D) | | in the neck of the pancreas, especially with extension into the body or tail. |
TREATMENT APPROACHES FOR PANCREATIC CANCER
Used for tumors in the pancreatic head or periampullary
region, the conventional Whipple procedure involves removal of the pancreatic head,
duodenum, gallbladder, and the antrum of the stomach, with surgical drainage of the distal
pancreatic duct and biliary system, usually through anastomosis to the jejunum. The
primary reason for removing so much of the intra-abdominal structures is that they all
share a common blood supply [24,102].
16 . Which chemotherapy agent/regimen has the strongest recommendation and level of evidence for use in patients with stage 3 (locally advanced) PDAC?
| A) | | Gemcitabine |
| B) | | Capecitabine |
| C) | | FOLFIRINOX |
| D) | | 5-FU continuous infusion |
TREATMENT APPROACHES FOR PANCREATIC CANCER
NCCN TREATMENT SUMMARY FOR PDAC
| Strength of Recommendation/Evidence | Regimen | Notesa |
|---|
| Adjuvant stage 1 (resectable) |
| Category 1 |
| Gemcitabine | | Gemcitabine/capecitabine | | 5-FU/leucovorin |
| – |
| Category 2a |
| 5-FU continuous infusion | | Chemoradiation |
| Chemoradiation should follow induction chemotherapy, with or without
subsequent chemotherapy |
| Category 2B | Capecitabine | – |
| Neoadjuvant stage 1/2 (resectable or borderline
resectable) |
| Category 2A | Gemcitabine/paclitaxel NAB | – |
| Category 2B |
| Gemcitabine/cisplatinb | | FOLFIRINOX | | Chemoradiation |
| – |
| Stage 3 (locally advanced) |
| Category 1 | Gemcitabine | Preferred for patients with poor ECOG PS (≥2) |
| Category 2A |
| Gemcitabine/paclitaxel NAB | | Gemcitabine/erlotinib | | Gemcitabine/cisplatinb | | Gemcitabine/capecitabine | | Gemcitabine fixed-dose rate | | FOLFIRINOX | | Chemoradiation |
|
| Fixed-dose rate gemcitabine is a category 2B recommendation for patients
with poor ECOG PS (≥2) | | Chemoradiation should follow induction chemotherapy, with or without
subsequent chemotherapy |
|
| Category 2B |
| Gemcitabine/docetaxel/capecitabine Capecitabine | | 5-FU continuous infusion | | FOLFOX |
| – |
| Stage 4 (metastatic) |
| Category 1 |
| Gemcitabine | | Gemcitabine/paclitaxel NAB (preferred) | | Gemcitabine/erlotinib | | FOLFIRINOX (preferred) |
| – |
| Category 2A |
| Gemcitabine/cisplatinb | | Gemcitabine/capecitabine | | Gemcitabine fixed-dose rate | | Olaparib | | Pembrolizumab (for MSI-H or dMMR tumors only) | | Larotrectinib (for NTRK-positive
only) |
|
| Fixed-dose rate gemcitabine is a category 2B recommendation for patients
with poor ECOG PS (≥2) | | Olaparib for maintenance therapy only in BRCA1/2 or PALB2 mutated
stage 4 disease without progression after 4 to 6 months of first-line
platinum-based therapy |
|
| Category 2B |
| Gemcitabine/docetaxel/capecitabine | | Capecitabinec | | 5-FU continuous infusionc | | FOLFOX | | Entrectinib (for NTRK-positive
only) |
| – |
| Second-line therapy |
| Category 1 |
| Gemcitabinec,d | | 5-FU/leucovorin/irinotecand |
| – |
| Category 2A | Gemcitabine fixed-dose rate | Fixed-dose rate gemcitabine is a category 2B recommendation for patients with
poor ECOG PS (≥2) |
| Category 2B |
| Capecitabinec,e | | 5-FU continuous infusionc,e |
| – |
| Strength of Recommendation Definitions |
| Category | Definition |
| 1 | Based upon high-level evidence, there is uniform
NCCN consensus that the intervention is appropriate. |
| 2A | Based upon lower-level evidence, there is
uniform NCCN consensus that the intervention is appropriate. |
| 2B | Based upon lower-level evidence, there is NCCN
consensus that the intervention is appropriate. |
| aECOG performance status (PS) 0/1 only,
unless noted. | | bIn BRCA1/2 or PALB2 mutations
only. | | cPoor ECOG PS (≥2) only. | | dIf prior non-gemcitabine-based
therapy. | | eIf prior gemcitabine-based therapy. |
|
17 . ASTRO guidelines for neoadjuvant chemoradiation specify a radiation dose of
| A) | | 450-500 cGy in 18-20 cGy fractions. |
| B) | | 1,500-2,040 cGy in 80-120 cGy fractions. |
| C) | | 4,500-5,040 cGy in 180-200 cGy fractions. |
| D) | | 6,500-7,400 cGy in 280-300 cGy fractions. |
TREATMENT APPROACHES FOR PANCREATIC CANCER
ASTRO guidelines for neoadjuvant chemoradiation specify
a radiation dose of 4,500–5,040 cGy in 180–200 cGy fractions [12]. They recommend delivery of radiation
therapy following two to six months of chemotherapy.
18 . To address bile duct obstruction in patients with PDAC, the preferred approach is
| A) | | ERCP. |
| B) | | cholecystectomy. |
| C) | | percutaneous approaches. |
| D) | | endoscopic retrograde stenting. |
PALLIATION AND SYMPTOMATIC MANAGEMENT
Endoscopic retrograde stenting is superior to surgical
or percutaneous approaches to address bile duct obstruction because of a more favorable
adverse event rate. Self-expandable metal stents are preferred over plastic stents in
patients with a life expectancy of more than three months in terms of patency duration,
less therapeutic failure and need for reintervention, lower cholangitis incidence, and
better patient quality of life. Patency rates between covered and uncovered metal stents
are not significantly different [16].
Endoscopic ultrasonography-guided biliary drainage is an alternative if endoscopic biliary
stent placement is unsuccessful or technically not feasible.
19 . Which agents have proven efficacy in the treatment of anorexia associated with cancer-related anorexia/cachexia syndrome?
| A) | | Cannabinoids |
| B) | | Antidepressants |
| C) | | Insulin and ghrelin |
| D) | | Corticosteroids and progesterone analogs |
PALLIATION AND SYMPTOMATIC MANAGEMENT
Many agents have been evaluated for the treatment of
CACS, but only corticosteroids (e.g., dexamethasone) and progesterone analogs (e.g.,
megestrol acetate) have a proven benefit in the anorexia associated with this syndrome
[122]. Selection is based on life
expectancy and assessment of risks versus benefits. Dexamethasone is suggested for
patients for whom only weeks of therapy are anticipated, while megestrol acetate or
medroxyprogesterone acetate (another progesterone analog) are suggested for patients with
longer life expectancies [126].
20 . When providing education to caregivers of patients with PDAC, which of the following points related to nutrition should be emphasized?
| A) | | Trying to force a patient to eat is usually counterproductive, potentially leading to increased nausea/vomiting. |
| B) | | Loss of appetite is common in patients with advanced cancer and may be the result of the cancer process itself. |
| C) | | Trying to make a patient eat, when they have marked appetite loss, can lead to decreased social interactions and increased patient distress regarding interactions with caregivers. |
| D) | | All of the above |
PALLIATION AND SYMPTOMATIC MANAGEMENT
Family members in particular can require educational
intervention, as their distress may manifest in attempts to pressure or coerce the patient
into increased feeding. Key points to discuss with patients and their family members,
related to interactions about nutrition and eating near the end of life, include the
following [131]:
Loss of appetite is common in patients with advanced cancer and may be the
result of the cancer process itself.
Trying to force a patient to eat is usually counterproductive, potentially
leading to increased nausea/vomiting.
In most patients with advanced cancer and cachexia, providing additional
calories by feeding tubes and/or intravenously does not improve outcomes.
Trying to make a patient eat, when they have marked appetite loss, can lead to
decreased social interactions and increased patient distress regarding interactions
with caregivers (including stories of patients, in their dying days, pretending to
be asleep when relatives visit, so that the relatives do not try to make them eat
something).
