Pancreatic Cancer

Course #90241 - $60-


Self-Assessment Questions

    1 . The median age at diagnosis of pancreatic cancer is
    A) 20 years.
    B) 40 years.
    C) 55 years.
    D) 70 years.

    EPIDEMIOLOGY

    During 2024 in the United States, an estimated 64,440 people will be diagnosed with pancreatic cancer, which represents 3.3% of all new cancer cases and the 11th most common new cancer diagnosis. The median age at diagnosis is 70 years [18].

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    2 . Of the following, which has the highest relative risk for pancreatic cancer?
    A) Obesity
    B) Family history
    C) Cigarette smoking
    D) Chronic pancreatitis

    EPIDEMIOLOGY

    COMMON RISK FACTORS FOR THE DEVELOPMENT OF PANCREATIC CANCER

    Factor Relative Risk
    Cigarette smoking1.7-fold to 2.6-fold
    Obesity1.1-fold to 1.5-fold
    Diabetes1.5-fold to 2-fold
    Family history1.7-fold to 2.3-fold
    Chronic pancreatitis13.3-fold
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    3 . 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.

    EPIDEMIOLOGY

    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].

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    4 . 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

    EPIDEMIOLOGY

    Numerous clinical series 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.

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    5 . 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).

    PATHOPHYSIOLOGY

    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 (<15%). However, all precursor lesions have key similarities [4,48,50]:

    • Early oncogene mutations initiate tumorigenesis.

    • Later loss of tumor suppressor genes drives tumor progression, high-grade dysplasia, and invasive cancer.

    • Increasing grades of dysplasia are associated with accumulation of somatic mutations in key driver genes.

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    6 . 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].

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    7 . All patients with pancreatic cancer should have germline testing and gene profiling offered
    A) only if requested by the patient.
    B) after one year of unsuccessful therapy.
    C) only if they have a positive family history.
    D) as quickly as possible after diagnosis.

    PANCREATIC CANCER SCREENING

    All patients with pancreatic cancer should have germline testing and gene profiling offered as quickly as possible after diagnosis; the implications for first-line therapy and beyond are significant [79,80]. The 2020–2021 ASCO and NCCN recommendations are for all patients with PDAC to receive germline genomic testing using comprehensive gene panels for hereditary cancer syndromes, and targeted (somatic) profiling of tumor tissue using next-generation sequencing [10,11]. Patients with locally advanced or metastatic PDAC should have available tumor tissue tested for DNA mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) status. It is also recommended that these patients undergo testing for actionable somatic mutations, including fusions (ALK, NRG1, NTRK, ROS1), mutations (BRAF, BRCA1/2, HER2, KRAS, PALB2), and mismatch repair deficiency (dMMR).

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    8 . 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 70%) originate in the head of the pancreas and present with biliary obstruction leading to dark urine (49%), jaundice (49%), loss of appetite (48%), weight loss (55%), and pancreatic insufficiency (25%) [134]. Symptoms of pancreatic cancer arising in the body and tail of the pancreas are more nonspecific, such as abdominal pain, back pain, weight loss and fatigue. Pancreatic cancers 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].

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    9 . In one study, the most common symptom of early-stage PDAC was
    A) nausea.
    B) fatigue.
    C) steatorrhea.
    D) abdominal pain.

    CLINICAL EVALUATION OF PANCREATIC CANCER

    Early-stage pancreatic cancer is notoriously difficult to diagnose. The most common symptoms in a series of patients diagnosed with PDAC were fatigue (86%), weight loss (85%), anorexia (83%), abdominal pain (79%), epigastric pain (71%), jaundice (56%), nausea (51%), diarrhea (44%), pruritus (32%), and steatorrhea (25%) [82].

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    10 . 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.

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    11 . Which of the following psychiatric issues is 11 times higher in men with PDAC compared with the general population?
    A) Suicide
    B) Attention deficit
    C) Aggression and violence
    D) Borderline personality disorder

    CLINICAL EVALUATION OF PANCREATIC CANCER

    A peculiar herald sign of occult pancreatic cancer is the insidious onset of an enigmatic depression, absent abdominal pain and often accompanied by anorexia and weight loss. In some patients, depression may be the most prominent presenting symptom, possibly secondary to delayed diagnosis. In addition, although patients may not communicate it to their families, they are often aware that a serious illness of some kind is occurring in them [24]. The risk of suicide among male patients with PDAC is almost 11 times higher than the general male population. Patients who underwent resection are more likely to commit suicide, specifically in the early postoperative period [83].

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    12 . 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].

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    13 . 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].

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    14 . Which of the following statements regarding pancreatic cancer cachexia is TRUE?
    A) It rarely develops in patients with PDAC.
    B) It typically responds well to therapeutic interventions.
    C) It is characterized by an increase in skeletal muscle mass.
    D) It is commonly associated with adipose tissue wasting and anorexia.

    CLINICAL EVALUATION OF PANCREATIC CANCER

    Pancreatic cancer cachexia is a multifactorial paraneoplastic syndrome characterized by a loss of skeletal muscle mass, commonly associated with adipose tissue wasting and anorexia, fatigue, and reduced exercise tolerance. Cachexia develops in approximately 80% of patients with PDAC, in whom the syndrome is typically present at diagnosis and responds poorly to therapeutic interventions [47,86].

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    15 . 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.

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    16 . All of the following are common laboratory abnormalities in patients with pancreatic cancer, EXCEPT:
    A) Mild anemia
    B) Decreased serum amylase
    C) Elevated serum bilirubin levels
    D) Elevated alkaline phosphatase levels

    CLINICAL EVALUATION OF PANCREATIC CANCER

    Routine laboratory tests are often abnormal but nonspecific for PDAC. Common abnormalities include an elevated serum bilirubin and alkaline phosphatase levels, and presence of mild anemia [84].

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    17 . 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 degree of contact between the tumor and local blood vessels (i.e., uninvolved, abutted, or encased) is used to define the most optimal initial treatment [134]. The NCCN recommends that MDCT angiography should also cover the chest and pelvis for complete staging [11].

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    18 . In patients with PDAC, biopsy
    A) can interfere with definitive surgery.
    B) is required before undergoing surgery.
    C) does not result in seeding if proper protocols are followed.
    D) will appropriately delay surgical resection if nondiagnostic.

    THE DIAGNOSTIC AND STAGING WORKUP

    Endoscopic ultrasound-guided biopsy is preferable to a CT-guided biopsy in patients with non-metastatic disease because of better diagnostic yield, safety, and lower risk of peritoneal seeding when compared with the percutaneous approach. Biopsy proof of malignancy is not required before surgical resection, and a non-diagnostic biopsy should not delay surgical resection when the clinical suspicion for pancreatic cancer is high [11]. However, when histologic confirmation of a pancreatic cancer diagnosis is required, as in certain situations, endoscopic ultrasonography-guided fine-needle core biopsy is the best modality for obtaining a tissue diagnosis.

    A pathologic diagnosis is indicated to confirm PDAC in locally advanced or metastatic disease, before neoadjuvant therapy, and in atypical presentations in which differential diagnosis is needed with other pancreatic masses (e.g., pancreatitis, lymphoma, tuberculosis). If a biopsy does not confirm malignancy, it should be repeated at least once [16].

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    19 . 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 not sufficiently sensitive or specific for routine screening, CA19-9 is the most clinically useful biomarker in PDAC, with sensitivity (79% to 81%) and specificity (82% to 90%) in symptomatic patients. A normal serum level is 37 U/mL [90].

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    20 . Patients with a pancreatic tumor 1–2 cm in greatest dimension would be staged
    A) Tis.
    B) T1c.
    C) T2.
    D) T3.

    THE DIAGNOSTIC AND STAGING WORKUP

    AMERICAN JOINT COMMISSION ON CANCER EXOCRINE PANCREATIC CANCER TNM STAGING

    Category Criteria
    Primary tumor (T)
    TXPrimary tumor cannot be assessed
    T0No evidence of primary tumor
    TisCarcinoma in situ, including high-grade PanIN (PanIN-3) and IPMN, ITPN, or MCN with high-grade dysplasia
    T1Tumor ≤2 cm in greatest dimension
    T1aTumor ≤0.5 cm in greatest dimension
    T1bTumor >0.5 and <1 cm in greatest dimension
    T1cTumor 1–2 cm in greatest dimension
    T2Tumor >2 and ≤4 cm in greatest dimension
    T3Tumor >4 cm in greatest dimension
    T4Tumor involves the celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size
    Regional lymph nodes (N)
    NXRegional lymph nodes cannot be assessed
    N0No regional lymph node metastasis
    N1Metastasis in one to three regional lymph nodes
    N2Metastasis in four or more regional lymph nodes
    Distant metastasis (M)
    M0No distant metastasis
    M1Distant metastasis
    IPMN = intraductal papillary mucinous neoplasm; ITPN = intraductal tubulopapillary neoplasm; MCN = mucinous cystic neoplasm; PanIN = pancreatic intraepithelial neoplasia
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    21 . 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)

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    22 . 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
    A) 1.
    B) 2.
    C) 3.
    D) 4.

    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
    5Deceased
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    23 . Which of the following is considered a curative treatment for PDAC?
    A) Chemotherapy
    B) Radical surgery
    C) Combination chemotherapy and radiation therapy
    D) There is no potentially curative treatment for PDAC.

    TREATMENT APPROACHES FOR PANCREATIC CANCER

    Curative surgical approaches for resectable pancreatic cancer are well-established. In contrast, the pace of new U.S. Food and Drug Administration (FDA) approvals and/or phase III evidence continue to make chemotherapy, molecular-targeted therapy, radiation, and chemoradiotherapy approaches a fluid, evolving area, requiring frequent updating and revisions in multidisciplinary clinical practice guidelines for pancreatic cancer treatment. Many potential treatment approaches lacking phase III or prospective evidence are being addressed, with publication of trial results awaited [2].

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    24 . 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].

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    25 . The cycle length of FOLFIRINOX chemotherapy for pancreatic cancer is
    A) 7 days.
    B) 14 days.
    C) 1 month.
    D) 3 months.

    TREATMENT APPROACHES FOR PANCREATIC CANCER

    CHEMOTHERAPY PROTOCOLS IN PANCREATIC CANCER

    DrugDose and RouteAdministrationGiven on Days
    Gemcitabine
    Indication: Nonmetastatic PDAC
    Cycle length: 4 weeks (once weekly for 3 weeks, then 1 week off)
    Gemcitabine1,000 mg/m2 IVDilute in 250 mL NS (concentration ≤40 mg/mL), administered over 30 minutes.Days 1, 8, and 15
    Gemcitabine and capecitabine (GemCap)
    Indication: Adjuvant therapy
    Cycle length: 28 days
    Duration: 6 months
    Gemcitabine1,000 mg/m2 IVDilute in 250 mL NS (concentration ≤40 mg/mL), administered over 30 minutes.Days 1, 8, and 15
    Capecitabinea830 mg/m2 per dose oralTwice daily (total 1,660 mg/m2 per day), 12 hours apart. Swallow with water within 30 minutes post-meal.Days 1 through 21
    Modified FOLFIRINOX
    Cycle length: 14 days
    Oxaliplatinb85 mg/m2 IVDilute in 500 mL D5W, administer over 2 hours (before leucovorin). Shorter schedules (e.g., 1 mg/m2 per minute) appear safe.Day 1
    Leucovorin400 mg/m2 IVDilute in 250 mL normal saline or D5W, administer over 2 hours (after oxaliplatin).Day 1
    Irinotecanc150 mg/m2 IVDilute in 500 mL normal saline or D5W, administer over 90 minutes concurrent with the last 90 mins of leucovorin infusion, in separate bags, using Y-line connection.Day 1
    Fluorouracil2,400 mg/m2 IVDilute in 500–1,000 mL 0.9% normal saline or D5W, administered as continuous IV infusion over 46 hours.dDay 1
    FOLFIRINOX
    Indication: Metastatic PDAC
    Cycle length: 14 days
    Oxaliplatinb85 mg/m2 IVDilute in 500 mL D5W, administer over 2 hours (before leucovorin). Shorter schedules (e.g., 1 mg/m2 per minute) appear safe.Day 1
    Leucovorin400 mg/m2 IVDilute in 250 mL normal saline or D5W, administer over 2 hours (after oxaliplatin).Day 1
    Irinotecanc150 mg/m2 IVDilute in 500 mL normal saline or D5W, administer over 90 minutes concurrent with the last 90 mins of leucovorin infusion, in separate bags, using Y-line connection.Day 1
    Fluorouracil400 mg/m2 IV bolusGive undiluted (50 mg/mL) as a slow IV push over 5 minutes (immediately after leucovorin).Day 1
    Fluorouracil2400 mg/m2 IVDilute in 500–1,000 mL 0.9% normal saline or D5W, administer as continuous IV infusion over 46 hours (immediately after IV bolus).dDay 1
    aCapecitabine is contraindicated in patients with known DPD deficiency.
    bMany centers routinely infuse oxaliplatin via central venous line because of local pain with infusion into a peripheral vein
    cConsider a lower dose of irinotecan with poor performance status.
    dTo accommodate an ambulatory pump for outpatients, can be administered undiluted (50 mg/mL) or the total dose diluted in 100–150 mL normal saline.
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    26 . 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/EvidenceRegimenNotesa
    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 2BCapecitabine
    Neoadjuvant stage 1/2 (resectable or borderline resectable)
    Category 2AGemcitabine/paclitaxel NAB
    Category 2B
    Gemcitabine/cisplatinb
    FOLFIRINOX
    Chemoradiation
    Stage 3 (locally advanced)
    Category 1GemcitabinePreferred 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 2AGemcitabine fixed-dose rateFixed-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
    CategoryDefinition
    1Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
    2ABased upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
    2BBased 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.
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    27 . 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.

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    28 . 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

    Symptomatic biliary obstruction develops in approximately 80% of patients with carcinoma of the head of the pancreas [143]. Biliary stents relieve troublesome pruritis and may be used to improve liver function sufficiently to permit safe administration of cancer treatment. Endoscopic retrograde stenting is superior to surgical or percutaneous approaches to address bile duct obstruction because of a more favorable adverse event rate. Successful biliary stent placement can be achieved in more than 90% of patients, with potential post-procedure complications of pancreatitis, bleeding, or cholangitis in 5% of cases [143]. 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.

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    29 . 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].

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    30 . 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

    Counselling of family members regarding what to expect with disease progression is important—it can alleviate distress that leads to well-meaning but futile 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).

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