Case study 89.1

1. A patient presented to the emergency room with acute-onset shortness of breath. A computed tomography (CT) angiogram of the chest revealed a segmental pulmonary embolism, for which the patient was started on anticoagulation with low-molecular-weight heparin. Limited imaging of the upper abdomen demonstrated a pancreatic head lesion with mixed cystic and solid components, interpreted as concerning for malignancy. She was referred to your office for further evaluation. What do you recommend as the next step in her diagnostic evaluation?

Positron emission tomography (PET)–CT
CT scan with multiphasic pancreatic protocol
Endoscopic ultrasound
Abdominal magnetic resonance imaging (MRI)
Endoscopic retrograde cholangiopancreatography (ERCP)

Cross-sectional imaging is imperative prior to any interventional procedure for a newly diagnosed pancreatic mass and is critical to careful selection of patients for whom there is a reasonable likelihood of an R0 resection. Optimal multiphase imaging must include a noncontrast phase plus arterial, pancreatic parenchymal, and portal venous phases of contrast enhancement with cuts that are ≤3 mm. Multiphasic protocols allow for selective visualization of critical arterial and venous structures with which to assess vascular invasion. Contrast enhancement is necessary to distinguish between a hypodense lesion in the pancreas and the parenchyma, and is greatest during the late arterial phase.

A pancreatic protocol CT scan is widely available and remains the best-validated imaging modality for diagnosis and staging of a patient with pancreatic ductal adenocarcinoma (PDAC). Pancreas protocol MRI is emerging as an alternative to CT and in 2012 was added to the National Comprehensive Cancer Network (NCCN) Guidelines as an option for the initial work-up of a pancreatic mass. While CT remains more widely available and is more cost-effective, MRI may provide the added advantage of increased sensitivity for the detection of small hepatic or peritoneal metastases in high-risk patients.

Endoscopic ultrasound (EUS) is complementary to CT as a confirmatory test for lesions that have questionable vascular or lymph node involvement. In particular, the accuracy of EUS in assessing the involvement of venous structures is high, but it is less accurate in evaluating the superior mesenteric artery (SMA) for tumor invasion. The role of PET–CT in the staging of PDAC is still evolving, although it has been demonstrated that PET–CT in combination with a standard CT protocol is associated with superior sensitivity for the detection of metastatic disease than standard CT alone or PET–CT alone (87% vs. 57% vs. 61%). ERCP is typically limited to therapeutic purposes for patients who require biliary decompression.

2. A CT scan with pancreatic protocol is performed and demonstrates a pancreatic head mass with dilation of the pancreatic duct distal to the mass. There are clear fat planes between the mass and the SMA and the hepatic artery, and there is no evidence of hepatic metastases. A CT scan of the chest is negative for metastases. A pathologic diagnosis has not yet been confirmed. What is the next step?

EUS with fine-needle aspiration (FNA)
ERCP
CT-guided percutaneous biopsy
Refer for resection

A histologic diagnosis can be obtained by FNA with either EUS guidance or CT guidance. EUS-directed FNA is preferred due to the higher diagnostic yield and safety, and the possible risk of peritoneal seeding with a percutaneous approach. However, for a patient with a tumor that appears resectable, a histologic diagnosis is not required prior to proceeding with surgical resection, and thus this patient should be referred for surgical resection without delay for additional diagnostic intervention. For patients who present with disease in which neoadjuvant chemotherapy is recommended, a pathologic diagnosis is imperative prior to initiation of chemotherapy.

Case study 89.2

1. A 56-year-old male presented to his primary care physician with darkening urine and pruritis. He reported a 3-month history of early satiety, 15-lb. weight loss, and greasy foul-smelling stools. A CT scan was ordered and revealed biliary constriction, with a 3 cm mass in the pancreatic head, without evidence of vascular invasion or metastatic disease. What is the next step in his management?

Percutaneous biliary drainage
Deployment of a plastic stent
Deployment of a metal stent
Refer for resection

For patients who present with resectable disease, preoperative biliary stenting does not decrease the mortality rate of a Whipple procedure. In a retrospective study of 240 consecutive patients who underwent pancreaticoduodenectomies at Memorial Sloan Kettering Cancer Center (MSKCC), those who underwent preoperative biliary decompression (53%) were subject to an increased rate of postoperative complications, including death, compared to those who were taken directly to surgery. In a randomized trial of 202 patients with cancers of the pancreatic head who presented with obstructive jaundice, a nearly twofold increase in the rate of serious complications was reported in the group who underwent preoperative stenting (74% vs. 39%). Based upon these reports, our practice for patients who present with jaundice and potentially resectable disease is to perform decompression only in patients who are symptomatic, are septic, or in whom surgery is delayed. Use of plastic stents is endorsed in these cases since patients typically do not require the longer patency of a metal stent. For patients who require neoadjuvant induction therapy prior to resection, biliary decompression with a short, expandable, metal stent is necessary prior to initiation of therapy.

2. The patient underwent an uncomplicated Whipple resection with negative surgical margins. A focus of metastatic adenocarcinoma was present in 1 out of 13 resected peripancreatic lymph nodes. He returns to your office 4 weeks after his surgery, with a well-healed surgical scar. He reports incremental improvements in his appetite and energy since his surgery. Which of the following should be performed prior to initiation of adjuvant therapy?

CT scan of the chest, abdomen, and pelvis
CA 19-9 measurement
PET/CT
A and B

CA19-9 is a tumor-associated antigen that requires the presence of sialylated Lewis (Le)^ablood group antigen for expression. While data are conflicting regarding the predictive significance of CA19-9 in response to chemotherapy, postoperative CA19-9 measurement is valuable as a prognostic marker for those patients whose tumors express the antigen. It is known that normalization of elevated CA19-9 levels by 3 to 6 months postoperatively is associated with longer median overall survival (OS). In a prospective study of patients undergoing surgery for PDAC with curative intent, there was a significant survival advantage for the group of patients with a postoperative CA 19-9 level of <180 U/mL, compared to those with higher postoperative CA19-9 levels (hazard ratio 3.53; P < 0.0001). CT restaging should also be performed in the postoperative setting to exclude the interval development of local recurrence of distant metastases, as this would certainly impact prognosis and possibly therapeutic decision making.

3. What form of adjuvant therapy do you recommend for this patient?

Gemcitabine-based chemoradiation (CRT)
Fluropyrimidine-based CRT
Gemcitabine alone for 6 months
5-fluorouracil (5-FU)–leucovorin for 6 months
There is no known benefit of any adjuvant therapy

The Charité Onkologie Clinical Studies in GI Cancers CONKO-001 trial randomized 354 patients without prior radiation or chemotherapy to adjuvant gemcitabine versus observation following curative surgery. Patients in the treatment arm had greater median disease-free survival (13.4 months vs. 6.9 months, P < 0.001); however, the median OS difference failed to reach statistical significance (22.1 vs. 20.2 months, P = 0.06), likely due to the fact that nearly all patients in the observation arm received gemcitabine upon relapse.

The ESPAC-1 trial tried to address the question of chemotherapy alone versus CRT. With a 2 × 2 factorial design, its four randomization schemes included observation, CRT, chemotherapy alone, and sequential CRT plus chemotherapy. In the end, the ability to answer this question was limited by the small sample size in each group, but this study did successfully demonstrate a positive impact on OS in the chemotherapy-only arm versus the observation arm. However, no survival benefit was seen in the CRT arm, which actually performed worse than the no-CRT arm.

In ESPAC-3, 1088 patients who underwent resection were randomized to receive six cycles of either 5-FU–leucovorin or gemcitabine. No differences were detected in median OS (23.0 vs. 23.6 months), progression-free survival (PFS) (14.1 vs. 14.3 months), or quality of life. Gemcitabine, however, was associated with significantly fewer serious adverse events.

The Radiation Therapy Oncology Group (RTOG) 97-04 trial randomized 451 patients with resected PDAC to receive either gemcitabine or 5-FU chemotherapy both before and after 5-FU-based CRT. For the patients with tumors of the pancreatic head, there was a nonstatistically significant increase in OS reported in the gemcitabine arm versus the 5-FU arm (20.5 vs. 16.9 months). This difference in OS was not evident in the recent 5-year analysis, but multivariate analysis showed a trend toward improved OS with gemcitabine in patients with tumors of the pancreatic head (P = 0.08).

As of this writing, no standard has been established in the adjuvant treatment of node-positive PDAC. The currently available clinical data are insufficient, but for patients in our practice who undergo a R0 resection and are found to have lymph node involvement on pathologic review, we recommend 6 months of adjuvant chemotherapy. In the absence of a contraindication, gemcitabine is preferred over 5-FU–leucovorin due to its favorable toxicity profile. Adjuvant chemotherapy should only be recommended in a patient who has adequately recovered from surgery, and it ideally should be initiated within 4–8 weeks. Further clarification regarding the role for adjuvant chemoradiation for patients who undergo R0 resection is anticipated from the ongoing intergroup trial, “A Phase III Trial Evaluating Both Erlotinib and Chemoradiation as Adjuvant Treatment for Patients with Resected Head of Pancreas Adenocarcinoma” (NCT01013649).

Case study 89.3

A 58-year-old man underwent a Whipple resection for recently diagnosed PDAC. He was referred to you by his surgeon for consideration of adjuvant therapy. You review his pathology report, which is notable for a positive pancreatic margin with 3 out of 15 lymph nodes involved with metastatic PDAC.

1. He is fit, and his postoperative recovery has been uncomplicated. What do you recommend?

CRT, followed by gemcitabine
Fluoropyrimidine-based CRT
Gemcitabine alone for 6 months
IMRT alone
There is no known benefit of any adjuvant therapy

The role for radiation therapy in the adjuvant setting remains unclear, although a subgroup analysis of data pooled from five randomized controlled trials of adjuvant therapy estimated that it is more effective than chemotherapy alone in patients with positive surgical margins. For patients who have a positive margin, upfront CRT followed by systemic chemotherapy is preferred. In subgroup analyses of CONKO-001, the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. Thus, our recommendation for this patient who underwent a R1 resection would be that he should initiate fluoropyrimidine-based CRT, followed by 6 months of gemcitabine.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Oncohema Key

Fastest Oncology & Hematology Insight Engine

89: Pancreatic Cancer

Related

Stay updated, free articles. Join our Telegram channel

Full access? Get Clinical Tree