Pancreatic Cancer Flashcards
Pancreatic Cancer
At about which vertebrae does the pancreas lie?
L1-2
Pancreatic Cancer
Regional drainage of pancreatic head
peripancreatic
pancreaticoduodenal*
porta hepatis*
celiac
superior mesenteric lymph nodes
*paraaortic (posterior tumors)
Pancreatic Cancer
Regional drainage of pancreatic body and tail
splenic artery (hilar)*
peripancreatic
(lateral suprapancreatic)*
celiac
superior mesenteric
paraaortic nodal basins*
Pancreatic Cancer
Generalized peritoneal involvement is more common with
carcinoma of which part of the pancreas?
body and tail
Pancreatic Cancer
Main venous drainage
portal system
Pancreatic Cancer
Which of the following is/are TRUE?
I. Positive physical findings, if any, generally reflect incurable disease.
II. At present, surgery offers the only means of cure.
III. The incidence of pancreatic cancer rises sharply after age 45, with higher
rates in females than in males (1.3:1) and in blacks compared with the general population
IV. Described risk factors for pancreatic cancer include chronic
pancreatitis, smoking, alcohol consumption, Helicobacter pylori infection, and
factors associated with metabolic syndrome such as obesity and glucose
intolerance
I, II, IV
***
III is false. (males > females)
Pancreatic Cancer
Jaundice and steatorrhea is more common with
carcinoma of which part of the pancreas?
head
Pancreatic Cancer
Only 10% of patients deemed unresectable because of vascular involvement by CT are truly inoperable at time of surgery.
TRUE or FALSE?
False.
Over 90%
Pancreatic Cancer
CT-guided biopsy facilitates FNA without exposing the peritoneum to potential tumor seeding, as may occur with EUS.
An advantage of EUS over CT is the ability to detect small or isoattenuating lesions, which might not be well visualized on cross-sectional imaging.
Sensitivity for EUS is at least comparable to CT, with tumor detection reported as high as 97%.
Only I is true Only I and II are true Only II and III are true Only I and III are true Only II is true Only III is true
All are true
None is true
II And III are true
I is false. ***Other way around
Pancreatic Cancer
What are the two standard procedure for the diagnosis and staging of pancreatic malignancies, in general.
HRCT and EUS.
Pancreatic Cancer
What staging procudre is helapful to assess for intraperitoneal metastases?
staging laparoscopy.
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the T stage:
2010 Tumor limited to the pancreas > 2 cm
2018 Tumor >2 and ≤4 cm
T2
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the T stage:
2010 Tumor involving the celiac axis and SMA
2018 and/or common hepatic artery, regardless of size
T4
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the T stage:
2010 Tumor beyond the pancrease but not involving the celiac axis and SMA
2018 Tumors >4 cm
T3
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the T stage:
Tumor 1–2 cm in greatest dimension
T1c (2018)
a - ≤0.5
b - >0.5 <1 cm
all less than 2 cm are “T1” in 2010.
Pancreatic Cancer AJCC staging (2010 or 2018)
What is:
N1
2010 - (+) regional lymph nodes
2018 - 1-3 RLN; 4 or more is N2 (no N2 in 2010)
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the stage group:
N2
Stage III
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the stage group:
N1 (except T4)
IIB
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the stage group:
T3, N0
IIA
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the stage group:
T2, N0
IB
Pancreatic Cancer AJCC staging (2010 or 2018)
Identify the T stage:
PanIn-3
Tis
Tis N0 M0 is Stage 0
Pancreatic Cancer
What are the criteria for disease resectability? (any site)
no distant metastasis
no arterial tumor contact (sma, ca, cha)
no tumor contact with SMV or PV; or ≤180 deg contact WITHOUT vein contour irregularity
Pancreatic Cancer
What are the criteria for disease borderline resectability? (head/uncinate)
solid tumor contact with:
- CHA
- SMA ≤180 deg
- variant arterial anatomy
- SMV/PV >180 with contour irregularity but with suitable vessel for reconstruction
- IVC
Pancreatic Cancer
What are the criteria for disease borderline resectability? (body/tail)
solid tumor contact with:
- CA ≤180 deg
- CA >180 deg without aorta and with intact GDA permitting Appleby
Pancreatic Cancer
What are the criteria for disease unresectability? (head/uncinate)
Solid tumor contact with:
- SMA >180
- CA >180
- first jejunal SMA branch
- Unreconstructible SMV/PV
- most proximal draining jejunal branch into SMV
Pancreatic Cancer
What are the criteria for disease unresectability? (body/tail)
Solid tumor contact with:
- > 180 SMA or CA
- CA and aortic involvement
- Unreconstructible SMV/PV
Pancreatic Cancer
What is the standard surgical treatment for pancreatic cancer of the head or uncinate?
Pancreaticoduodenectomy, first described by Whipple et al. in 1935.
Pancreatic Cancer
What is the standard surgical treatment for pancreatic cancer of the tail?
distal pancreatectomy +/- splenectomy
Pancreatic Cancer
How many lymph nodes harvested constitute an adequate assessment?
12 to 15
Pancreatic Cancer
What is the most common cause of death in patients with locally advanced/metastatic disease?
hepatic failure
mets or obstruction
Pancreatic Cancer
What is the usual superior and inferior extent of an APPA field?
T11 vertebral body (celiac vessels)
L2-3 (SM lymph nodes, D3)
Pancreatic Cancer
What is the usual anterior and posterior extent of lateral fields?
- 5 to 2.0 cm beyond initial gross disease
1. 5 cm behind the anterior portion of the vertebral body (paraaortic)
Pancreatic Cancer
Adjuvant Treatment
GITSG conducted the first
multicenter prospective trial of adjuvant CRT for patients with resected pancreatic cancer and negative surgical margins, laying the foundation for the
adoption of CRT in the United States.
Two-year OS was 42% in the CRT group versus 15% in the
surgery-alone arm.
Although with promising results,
why was this study criticized?
old EBRT techniques
CRT is difficult to evaluate effect of either treatment alone.
noncompliance in the CRT arm
Pancreatic Cancer
Adjuvant Treatment
In contrast to the GITSG, the EORTC sought to confirm the findings of the previous study.
Longterm
follow-up of the EORTC trial demonstrated no difference in 5-year OS with
CRT use: 22% (surgery alone) versus 25% (CRT). Post hoc analysis of
pancreatic head lesions failed to demonstrate a benefit with CRT, with a median
OS of 1.3 years for CRT versus 1 year for surgery alone.
Why was this study criticized?
inclusion of periampullary ca
older EBRT techniques
inclusion of patients who underwent noncurative resection
no maintenance chemo after CRT.
Pancreatic Cancer
Adjuvant Treatment
Which study with three parallel arms showed that
adjuvant CRT was associated with a deleterious effect on survival?
ESPAC
Pancreatic Cancer
Adjuvant Treatment
Despite the negative effect on CRT on survival as shown in ESPAC-2 (2x2 analysis),
why should this data be used with caution?
not powered to detect OS difference.
***
Additionally, old EBRT techniques,
possible bias in randomization,
noncompliance to treatment
Pancreatic Cancer
Adjuvant Treatment
What European phase III trial showed 5-year OS improvement with adjuvant gemcitabine vs. observation?
Charite Onkologie (CONKO)
Pancreatic Cancer
Adjuvant Treatment
What is this largest randomized trial in pancreatic cancer that compared adjuvant 5-FU vs gemcitabine?
At a median follow-up of 34.2 months, there was no
difference between the two groups in the primary end point of OS.
ESPAC-3
Pancreatic Cancer
Adjuvant Treatment
What is this largest randomized trial in pancreatic cancer that tested the addition of capecitabine to gemcitabine alone which concluded that adjuvant gemcitabine and
capecitabine may be a reasonable alternative to single-agent gemcitabine?
ESPAC-4
Pancreatic Cancer
Neoadjuvant Treatment
Which is FALSE regarding the rationale behind neoadjuvant chemotherapy.
I. Approximately one-third of patients experience a significant delay or do no receive adjuvant therapy following resection.
II. Twenty percent to 40% of patients will be spared the morbidity of resection as their metastatic disease becomes clinically apparent during course of neoadjuvant therapy.
III. Preoperative therapy could theoretically be less toxic and more effective as the chemotherapy and radiation would be given without the postsurgical issues of small bowel in the radiation field, decreased oxygenation and decreased drug delivery to the remaining tumor bed.
IV. Patients with local, borderline, and unresectable lesions may be able to be downstaged to allow for surgical resection and sterilization of the operative region, which potentially facilitates R0 resection and reduces the risk of spread during surgical manipulation.
None
Pancreatic Cancer
Adjuvant Treatment
This trial which compared adjuvant chemotherapy (5 FU vs gemcitabine) followed by CRT had a secondary aim of assessing the ability of posteresection CA 19-9 levels.
When CA19-9 levels were analyzed in a
cohort of 385 patients as a dichotomized variable (<180 IU/mL vs. ≥180 IU/mL,
≤90 IU/mL vs. >90 IU/mL), there was a significant survival difference favoring
patients with CA19-9 levels of <180 IU/mL.
RTOG 9704
Pancreatic Cancer
Neoadjuvant Treatment
With recent data demonstrating efficacy of combination chemotherapy in the metastatic setting, there has been growing interest to assess these agents in less advanced disease.
The ongoing Southwest Oncology Group (SWOG) phase II study is comparing neoadjuvant gemcitabine and nab-paclitaxel to m-FOLFIRNOX for resectable pancreatic adenocarcinoma.
The goal of this study is to identify the superior arm to test in a larger randomized trial. (https://clinicaltrials.gov/show/NCT02562716).
Side question.
What is FOLFIRNOX?
FOL-inic acid
F-U
IRN-otecan
OX-aliplatin
Pancreatic Cancer
LAPC
The GITSG compared EBRT alone to EBRT
with concurrent and maintenance 5-FU.
194 eligible patients with surgically confirmed unresectable and nonmetastatic pancreatic
adenocarcinoma were randomized to receive 60-Gy split-course EBRT alone,
40-Gy split-course EBRT with 2 to 3 cycles of concurrent bolus 5-FU
chemotherapy (500 mg/m2), or 60-Gy split-course EBRT using a similar
chemotherapy regimen.
What were the findings?
The EBRT-alone arm
was closed early as a result of an inferior survival rate. The 1-year survival rate
in the two combined modality therapy arms was roughly 40% (with no statistical
difference between CRT arms) versus 11% in the EBRT-alone arm.
Pancreatic Cancer
LAPC
The ECOG-8282 randomized 114 patients to EBRT alone (59.4 Gy) with or without continuous infusion 5-FU (1,000 mg/m2/d) on days 2 to 5 and 28 to 31 and mitomycin-C (10 mg/m2) on day 2.
What were the findings?
There was no difference in response rates, DFS, or OS with the addition of
concurrent chemotherapy.
Higher rates of toxicity, primarily hematologic, were
noted in the CRT group
Pancreatic Cancer
LAPC
A second GITSG trial randomized 157 and analyzed results for 143 eligible
patients with unresectable disease to 60-Gy split-course EBRT with concurrent
and maintenance 5-FU (500 mg/m2) (as in the prior GITSG trial) or 40-Gy
continuous course radiation with weekly, concurrent doxorubicin chemotherapy
(10 mg/m2), followed by maintenance doxorubicin and 5-FU.
A significant
increase in treatment-related toxicity was seen in the doxorubicin arm, with no
survival difference observed between the two groups (median survival 8.5 vs.
7.6 months).
No clinical benefit was seen in substituting doxorubicin for 5-
FU
Pancreatic Cancer
LAPC
“ECOG vs. GITSG”
Which group showed a significant survival advantage for CRT over CT alone?
(54 Gy+5FU+SMF vs. SMF)
Which group showed no benefit to CRT vs. CT only?
(40 Gy + 5 FU vs. 5-FU)
Which group showed no difference in DFS but detected a survival benefit for the CRT arm?
(50.4Gy+gemcitabine vs. gemcitabine)
GITSG
ECOG
ECOG
Pancreatic Cancer
LAPC
Based on the phase II SCALOP trial.
Which agent was preferable in the concurrent setting?
capecitabine vs. gemcitabine
Capecitabine
***
Seventy-four patients
were randomized and median OS in the capecitabine group was 15.2 months
compared with 13.4 months in the gemcitabine arm (P = .012). More patients in
the gemcitabine group than in the capecitabine group had grade 3 to 4
hematologic toxicity and grade 3 to 4 nonhematologic toxicity during CRT.
Pancreatic Cancer
Borderline Resectable
In the neoadjuvant setting, what is the usual RT dose given with concurrent chemotherapy?
50.4/28
Pancreatic Cancer
Dose Escalation
A phase I/II study by Ben Josef
et al. attempted to define the maximum tolerated radiation dose via IMRT in combination with gemcitabine for unresectable pancreas cancer.
Fifty patients were accrued and dose-limiting toxicity was seen at ___Gy.
55
Pancreatic Cancer
SBRT
RT doses
25/25/1
(91% freedom from local progression, no g3 acute, 9% g3 late toxicity, hence succeeding studies utilizing 5 fractions)
33/6.6/5
Pancreatic Cancer
(from in-service bank)
- A 58 year-old male was diagnosed with pancreatic head adenocarcinoma, KPS 80, no jaundice and abdominal CT (pancreas protocol) showing abutment but not encasement of the superior mesenteric vessels. Staging revealed no evidence of distant metastasis. Multidisciplinary tumor board was convened and you are the attending radiation oncologist.
The surgical specialist advised neoadjuvant treatment as he was concerned with the proximity of the tumor to the superior mesenteric vessels. After review of the available imaging, the consensus was to perform neoadjuvant treatment.
With currently available data, what would you recommend as the treatment of choice?
A. Chemoradiotherapy as the latest randomized trial showed a 3 month benefit in overall survival (PREOPANC-1)
B. Total neoadjuvant Gemcitabine-abraxane as found superior in the MGH Phase II neoadjuvant trial
C. Total neoadjuvant FOLFIRINOX as found superior in the MGH Phase II neoadjuvant trial
D. 3 cycles neoadjuvant 5-fluorouracil with folinic acid, which is still the standard neoadjuvant treatment for borderline resectable pancreatic cancer
C
Pancreatic Cancer
(from in-service bank)
13. In patients who have had an R1, and in select patients who have had an R0 resection for pancreatic cancer, the most appropriate post-operative management is \_\_\_\_\_\_. A. Close monitoring B. Post-operative radiotherapy C. Post-operative chemoradiotherapy D. Post-operative chemotherapy
D
Pancreatic Cancer
(from in-service bank)
- Based on the ESPAC series of trials on the post-operative management of pancreatic cancer, the standard treatment for patients requiring adjuvant treatment is _______.
A. FOLFOX chemotherapy
B. Single-agent gemcitabine chemotherapy
C. 45 Gy external beam radiotherapy + continuous infusion 5FU+FA
D. FOLFIRINOX chemotherapy
D
Pancreatic Cancer
(from in-service bank)
15. The radiation dose fractionation scheme in the PREOPANC-1 trial was \_\_\_\_\_\_. A. 30 Gy in 10 fractions B. 36 Gy in 15 fractions C. 45 Gy in 25 fractions D. 50.4 Gy in 28 fractions
B
Pancreatic Cancer
(from in-service bank)
- In the phase III SFRO trial in locally-advanced pancreatic cancer, the standard of care in unresectable disease is ______.
A. Standard fractionated radiotherapy alone
B. Stereotactic ablative body radiotherapy
C. Standard fractionated radiotherapy with cisplatin and 5-FU followed by maintenance gemcitabine
D. Gemcitabine alone
D
Pancreatic Cancer
(from in-service bank)
- A 51 year old male patient (ECOG 0-1) with pancreatic head adenocarcinoma underwent 6 cycles of neoadjuvant gemcitabine with albumin-bound paclitaxel for borderline resectable disease. Post-chemotherapy abdominal CT scan showed no progression of the primary, though there was solid tumor contact with the common hepatic artery without extension to the celiac axis and the hepatic artery bifurcation. There was still no evidence of distant metastasis. Your opinion as a radiation oncologist is needed by the multidisciplinary team, especially since the patient has already maximized gemcitabine-based chemotherapy. Which among the following will help you in your decision regarding the next step in the management of this patient?
A. Although using an older chemotherapy regimen (gemcitabine or gemcitabine + erlotinib), the LAP-07 trial showed a decrease in local progression (32% vs 46%) with the addition of chemoradiation.
B. A statistically significant overall survival benefit was seen with preoperative chemoradiation (3 cycles of gemcitabine, the second combined with radiotherapy) in the PREOPANC trial)
C. Preoperative chemoradiation has been reported to improve the R0 resection rates, disease-free survival, and locoregional failure-free interval in the study by the Dutch Pancreatic Cancer Group phase III trial
D. The patient may already be an appropriate candidate for surgery, especially since your institution is considered a high-volume center for pancreatic cancer resections (10 cases per year).
C
