Pancreatic and periampullary adenocarcinoma

Question 1

Appx how many pancreatic adenocarcinoma (PCA) pts are diagnosed per yr in the United States?

Answer 1

As of 2016, the incidence of PCA is 53,670 cases/yr in the United States, with 43,090 deaths. Its incidence is higher in developed countries

Question 2

Where does PCA rank in cancer incidence in the United States? Cancer
mortality?

Answer 2

As of 2016, PCA is the 12th most common cancer Dx but the 4th most common cause of cancer death in the United States.

Question 3

Is there a racial or sex predilection for PCA?

Answer 3

Yes. African Americans are more commonly affected than Caucasians; however, the incidence is similar among males and females.

Question 4

In what decades of life does PCA incidence peak?

Answer 4

The peak age of PCA is in the 6th–7th decades of life.

Question 5

What are 3 environmental exposures associated with PCA?

Answer 5

Most common environmental risk factors for PCA:

1. Tobacco smoking
2. 2-naphthylamine
3. Benzidine

Question 6

What % of PCA is familial?

Answer 6

∼10% of PCA is familial.

Question 7

What 2 genetic mutations have most frequently been associated with familial PCA?

Answer 7

p16 and BRCA2 are the 2 most common familial associated genetic changes
found in PCA.

Question 8

Is chronic pancreatitis associated with increased risk of PCA?

Answer 8

No. Chronic pancreatitis is not associated with risk of PCA. Historically, there appeared to be an association, but this can be explained by confounding
factors.

Question 9

Appx at what vertebral bodies are the pancreas, celiac axis, and superior
mesenteric artery (SMA) located?

Answer 9

Pancreas: L1–2
Celiac axis: T12
SMA: L1

Question 10

What % of PCA arise in the head, body, and tail of the pancreas?

Answer 10

Common PCA sites are 75% in the head, 15% in the body, and 10% in the
tail.

Question 11

What is the distribution of local, regional, and metastatic Dz at Dx?

Answer 11

10% of PCA pts have local Dz at Dx.
25% of PCA pts have regional node+ Dz at Dx.
50% of PCA pts have DM at Dx.

Question 12

For PCA, what are the 3 most common sites of DM?

Answer 12

Common sites of DM for PCA include the liver, peritoneum, and lungs.

Question 13

Is there a role for screening in PCA?

Answer 13

No. There is no current role for PCA screening. There are studies evaluating
the role of screening 1st-degree relatives of PCA with EUS, but this is still
experimental.

Question 14

What % of pancreatic tumors are from the exocrine pancreas?

Answer 14

95% of PCA are from the exocrine pancreas.

Question 15

What are the 4 most common pathologic subtypes of exocrine pancreatic tumors?

Answer 15

Most common subtypes of exocrine pancreatic tumors:

1. Ductal adenocarcinoma (80%)
2. Mucinous cystadenocarcinoma
3. Acinar cell carcinoma
4. Adenosquamous carcinoma

Question 16

What are the most common oncogenes in PCA?

Answer 16

K-ras oncogene is present in >95% of PCA.
p16 mutations are seen in >90% of PCA.
p53 mutations occur in 55%–75% of PCA.
DPC4 mutations occur in ∼50% of PCA.

Question 17

What are the most common presenting signs & Sx of PCA?

Answer 17

Common presenting signs & Sx of PCA are pancreatic/biliary duct
obstruction, jaundice, and abdominal pain.

Question 18

What Dz is commonly diagnosed 1–2 yrs prior to a PCA Dx?

Answer 18

60%–80% of PCA pts are diagnosed with diabetes 1–2 yrs prior to Dx.
However, only a small proportion of diabetic pts develop PCA.

Question 19

Periampullary cancers refer to tumors arising from what 4 structures?

Answer 19

Periampullary tumors are those arising from the ampulla of Vater, common
bile duct (CBD), head of the pancreas, and adjacent duodenum.

Question 20

What is the DDx of a pancreatic mass?

Answer 20

The DDx of a pancreatic mass includes exocrine cancer, islet
cell/neuroendocrine cancer, cystic adenomas, papillary cystic neoplasms (e.g., intraductal papillary mucinous tumor), lymphoma, acinar cell carcinoma, and metastatic cancer.

Question 21

What is the initial workup for suspected PCA?

Answer 21

Suspected PCA workup includes a focused H&P, labs including CBC, CMP,
and CA 19-9, and abdominal CT scan.

Question 22

In what circumstance will a PCA pt not excrete any CA 19-9?

Answer 22

If a pt is red cell Lewis antigen A–B negative, then the pt cannot excrete
CA 19-9. The Lewis antigen– phenotype is present in 5%–10% of the
population.

Question 23

What is the appropriate imaging for suspected PCA?

Answer 23

Dual-phase thin-sliced (preferably submillimeter) CT abdomen, with images
obtained in the pancreatic parenchymal and portal venous phases of
enhancement.

Question 24

Name 4 appropriate procedures for obtaining tissue from a suspicious
pancreatic mass.

Answer 24

Procedures to obtain tissue from a suspicious pancreatic mass:

1. EUS-guided FNA
2. CT-guided FNA
3. Endoscopic retrograde cholangiopancreatography (ERCP)
4. Pancreatic resection (i.e., histologic Dx is not required before Sg)

Question 25

When is it appropriate to obtain tissue prior to Sg for lesions suspicious on
imaging?

Answer 25

Tissue Dx prior to Sg is not routinely necessary, except for: (1) clinical trial enrollment, (2) prior to neoadj therapy, or (3) prior to chemo/CRT in unresectable pts.

Question 26

What is the major advantage of EUS-guided FNA over CT-guided FNA of a pancreatic mass?

Answer 26

EUS-guided FNA is associated with lower risk of peritoneal seeding (2%
vs. 16%).

Question 27

When is ERCP indicated instead of EUS?

Answer 27

ERCP carries a higher risk of iatrogenic pancreatitis, so it is reserved for cases where PCA is causing biliary obstruction and cholangitis requiring stenting.

Question 28

What is the NCCN 2018 classification scheme for PCA?

Answer 28

PCA are classified into 4 categories

1. Resectable (T1–3N0 or N+)
2. Borderline resectable (T1–4Nany)
3. Locally advanced unresectable (T4Nany)
4. Metastatic (TanyNanyM1)

Question 29

What 3 criteria are necessary for a primary pancreatic tumor to be
resectable (per NCCN)?

Answer 29

NCCN resectability for PCA is defined as:
1. No distortion of superior mesenteric vein (SMV) or portal vein (PV) &
≤180-degree contact
2. Clear fat plane around celiac artery, SMA, and common hepatic artery
(CHA)
3. No distant mets or mets to nodes beyond field of resection

Question 30

What characteristics make a primary pancreatic tumor unresectable (per NCCN)?

Answer 30

Unresectable characteristics include:

1. > 180-degree encasement of SMA, celiac axis, first jejunal branch of SMA for head lesions
2. > 180-degree encasement of the SMA, celiac axis, or abutment of CA w/ aortic involvement for body/tail lesions
3. Unreconstructable SMV/PV occlusion, contact w/ most proximal draining jejunal branch of SMV
4. Aortic invasion/encasement

Question 31

What are the characteristics of borderline resectable pancreatic head/body
tumors (per NCCN)?

Answer 31

The definitions vary, but NCCN definition of borderline resectability for
PCA are:
1. SMV/PV involvement (distortion, narrowing or occlusion) that can be
resected and reconstructed using nearby vessels.
2. Tumor abutment on SMA ≤180 degrees, CHA abutment without extension
to celiac axis or hepatic bifurcation.
3. Gastroduodenal artery encasement up to the hepatic artery, including up to short segment encasement or direct abutment of the hepatic artery, without celiac axis involvement.

Question 32

What pancreatic tail lesions are considered “borderline resectable”?

Answer 32

Invasion into the adrenal gland, colon, mesocolon, or kidney are considered borderline resectable for PCA tail lesions

Question 33

What location of PCA is associated with higher rates of resectability: head, body, or tail?

Answer 33

PCA head tumors are more resectable b/c they cause Sx early (and therefore
present with earlier-stage Dz).

Question 34

At presentation, what % of PCA pts are resectable?

Answer 34

10%–20% of PCA pts are potentially resectable at presentation.

Question 35

What % of pts with resectable PCA tumors by CT imaging will be
resectable at the time of Sg?

Answer 35

∼65%–80% of PCA pts deemed resectable by CT are resectable at the time
of Sg.

Question 36

What is the role of staging laparoscopy?

Answer 36

Staging laparoscopy at the time of Sg is not routinely warranted. Select pts
with tumors >3 cm, tumors in the body/tail, equivocal CT findings of mets, or
CA 19-9 >100 U/mL may benefit

Question 37

What imaging is indicated to assess for metastatic Dz?

Answer 37

CT chest with contrast is routinely performed for metastatic workup of PCA.
PET-CT may be more sensitive for systemic Dz, but is not yet standard.

Question 38

What is the significance of a postresection CA 19-9 >90 U/mL?

Answer 38

In RTOG 9704, 53 pts (14%) had CA 19-9 >90 U/mL, and only 2 of these
pts survived up to 3 yrs.

Question 39

What is the AJCC 8th edition (2017) T and N staging for PCA?

Answer 39

T1: tumor size ≤2 cm
T1a: ≤0.5 cm
T1b: >0.5 cm and <1
T1c: ≥1cm and ≤2 cm
T2: tumor size >2 cm and ≤4 cm
T3: Tumor size >4 cm
T4: celiac axis, SMA, or CHA involvement

N1: 1–3 regional nodes
N2: ≥4 regional nodes

Question 40

What are the AJCC 8th edition (2017) stage groupings for PCA?

Answer 40

Stage 0: Tis
Stage IA: T1N0M0
Stage IB: T2N0M0
Stage IIA: T3N0M0
Stage IIB: T1–3N1M0
Stage III: T1–3N2, T4 Any N M0
Stage IV: Any T Any N M1

Question 41

What is the stage of a PCA pt with positive cytology at time of laparoscopy?

Answer 41

Positive cytology is stage IV (M1).

Question 42

Does the AJCC 8th edition (2017) TNM staging for ampullary, bile duct, and duodenal cancer differ from PCA?

Answer 42

Yes.

Question 43

What is the 5-yr OS for all stages of PCA?

Answer 43

5-yr OS is 7% for all stages of Dz combined

Question 44

What surgical procedure is required to resect a pancreatic head lesion?

Answer 44

Sg utilized for pancreatic head resection includes pylorus-preserving pancreaticoduodenectomy (PPPD) or classic pancreaticoduodenectomy
(Whipple procedure).

Question 45

What anastomoses are performed in the classic pancreaticoduodenectomy
(Whipple)?

Answer 45

There are 3 anastomoses performed for the Whipple procedure:

1. Pancreaticojejunostomy
2. Choledochojejunostomy (hepaticojejunostomy)
3. Gastrojejunostomy

Question 46

What are the 4 most favorable prognostic factors after resection?

Answer 46

Most favorable prognostic factors after resection of PCA:

1. Negative margins (R0)
2. Low grade (G1)
3. Small tumor size (<2 cm)
4. N0 status

Question 47

What is the modern MS for unresectable, margin– resected, and margin+
resected PCA pts?

Answer 47

The MS for PCA pts with the following surgeries in the era of adj and
definitive CRT is:
1. Unresectable ∼13 mos
2. Margin+ resection ∼16–18 mos
3. Margin− resection ∼25 mos

Question 48

What is the current mortality rate for pancreaticoduodenectomy?

Answer 48

At tertiary care centers with high throughput (min 15–20/yr), the mortality
rate for pancreaticoduodenectomy is <4%.

Question 49

What is the most feared complication for pancreaticoduodenectomy?

Answer 49

Anastamotic leaks are the most important complications after
pancreaticoduodenectomy and can lead to peritonitis, abscess, autodigestion,
hemorrhage, and delayed gastric emptying.

Question 50

Is there a benefit to R1 or R2 resection over definitive CRT for PCA?

Answer 50

No. Retrospective evidence suggests that survival is similar b/t PCA pts who
had R1 or R2 resection and definitive CRT. Therefore, planned resections should be done in pts where R0 resections are likely. Debulking Sg does not
improve outcome over definitive CRT.

Question 51

Should pts with resectable PCA undergo extended retroperitoneal lymphadenectomy?

Answer 51

No. Resectable PCA pts should not undergo an extended retroperitoneal
lymphadenectomy. There is no survival benefit to extended lymphadenectomy by an RCT (5-yr 25% vs. 31%, NSS). (Riall TS et al., J
Gastrointest Surg 2005)

Question 52

Can definitive CRT replace surgical resection for resectable PCA?

Answer 52

No. Sg alone is sup to CRT alone for pts with resectable PCA per the
Japanese PCA Study Group in an RCT of Sg alone vs. definitive CRT (50.4
Gy with continuous infusion (CI) 5-FU). The trial was stopped early d/t the
benefit of Sg: MS was 12 mos vs. 9 mos, and 5-yr OS was 10% vs. 0%. (Doi
R et al., Surg Today 2008)

Question 53

What are the adj Tx options for a PCA pt s/p resection?

Answer 53

Adj Tx options after a pancreaticoduodenectomy:
1. Adj gemcitabine (CONKO-001)
2. Adj gemcitabine alone → 5-FU/RT→ gemcitabine alone (RTOG 9704)
3. Adj 5-FU/RT (GITSG 91–73); consider maintenance gemcitabine
afterward
4. Adj 5-FU → 5-FU/RT → 5-FU (RTOG 9704)
5. Observation alone

Question 54

What is the standard postop RT Tx volume, dose, and fractionation for PCA?

Answer 54

Standard adj RT volume includes tumor bed, anastomoses (pancreaticojejunostomy and choledochojejunostomy), and LN basin (peripancreatic, celiac, sup mesenteric artery, porta hepatis, and aortocaval). The initial volume is treated to 45 Gy in 1.8 Gy/fx with a cone down to 50.4– 54 Gy to the surgical bed depending on extent of resection. Keep max small bowel dose <51 Gy.

Question 55

For pts with resected PCA, LF is the site of 1st failure for what % of pts treated with adj CRT? Distant failure as the 1st site?

Answer 55

Based on RTOG 9704, LF was site of 1st failure in 28% of PCA and distant
failure was 1st site in 73%.

Question 56

What U.S. study 1st reported a benefit of adj CRT vs. no additional Tx for
resected PCA? Describe the arms of this study and the major results.

Answer 56

The GITSG 91–73 trial 1st reported benefit to adj CRT for PCA in 1985. All
pts had R0 resections.
Standard arm: postop observation
Experimental arm: adj CRT using split-course RT to 40 Gy (2-wk break after 20 Gy) with intermittent bolus 5-FU → 2 full yrs of adj 5-FU alone
Improved MS (20 mos vs. 11 mos) and 2-yr OS (42% vs. 15%) in the adj CRT arm. (Kalser MH et al., Arch Surg 1985)

Question 57

Did the EORTC 40891 study on PCA support or contest the benefit of adj CRT?

Answer 57

Support. The EORTC 40891 trial used the same randomization as GITSG
91–73, except the Tx arm did not rcv maintenance adj 5-FU for 2 yrs. Median PFS was 17 mos (CRT) vs. 16 mos (observation), NSS; MS was 24 mos (CRT) vs. 19 mos (observation), NSS. For the subset of PCA pts, 5-yr OS
was 20% (CRT) vs. 10% (observation) (p = 0.09) (Klinkenbijl JH et al., Ann Surg 1999). Of note, in addition to T1–2N0–1 PCA, 45% of pts had periampullary adenocarcinoma, which were excluded in GITSG 91–73, and generally have better prognosis. Authors concluded that routine adj CRT was not warranted, although statistical reanalysis of this study found a significant survival benefit with adj therapy. (Garofalo MC et al., Ann Surg 2006)

Question 58

Did the ESPAC-1 study on PCA support or contest the benefit of adj CRT?

Answer 58

Contest. ESPAC-1 included pts with grossly resected adenocarcinoma of the pancreas. The study used a 2 × 2 factorial design; Sg +/− CRT and +/− adj chemo. Adj CRT was similar to GITSG. Adj chemo was 6 mos of 5-FU. MS was 15 mos (CRT) vs. 16 mos (no CRT), NSS; OS was 20 mos (chemo) vs. 14 mos (no chemo) (p = 0.0005).
Criticisms: Physicians could randomize pts into 2 × 2 or directly into 1 of the 2 randomizations. “Background Tx” was allowed (i.e., observed pts may have rcvd chemo +/− RT). There was no central RT QA. (Neoptolemos JP et al., Lancet 2001) Note: Analysis of 2 × 2 subset suggests that CRT had a
deleterious effect; 5-yr OS was 10% (CRT) vs. 20% (no CRT) (p = 0.05).

Question 59

How does the presence of a +margin after resection for PCA influence the decision for adj CRT?

Answer 59

UK Clinical Trials Unit meta-analysis of 5 RCTs, including individual data from 4 RCTs, found that the benefit of adj CRT was greater in R1 pts
compared to R0 pts, although the difference was not SS. Also, the benefit
of adj chemo alone decreased in R1 pts compared to R0 pts, suggesting that CRT may have a more important role in R1 pts. (Butturini G et al., Arch Surg 2008) This is being examined in RTOG 0848, which randomizes postop pts, stratified by margin status, to either chemo alone or CRT after 5 cycles of induction chemo.

Question 60

Which study supports the role for adj gemcitabine for resected PCA over best supportive care? What subset of pts were excluded from this trial?

Answer 60

CONKO-001 included T1–T4, N0–N1 pts in an RCT of observation vs. adj
gemcitabine. Outcomes favored adj Tx: median DFS was 13 mos vs. 7 mos (SS). MS was 23 mos vs. 20 mos (SS), and 5-yr OS was 21% vs. 10% (SS), 10-yr OS was 12.2% vs. 7.7%. (Oettle H et al., JAMA 2013) Note: Pts with CA 19-9 >90 (2.5 × upper limit of normal [ULN]) were excluded from this
trial.

Question 61

What study compared adj 5-FU to gemcitabine following surgical resection?

Answer 61

ESPAC-3 showed an MS of 23 mos for pts treated with 5-FU (and folinic acid) vs. 23.6 mos for pts treated with gemcitabine (NSS). (Neoptolemos JP et al., JAMA 2010)

Question 62

Did the study RTOG 9704 on PCA support or contest a benefit of gemcitabine-based adj CRT?

Answer 62

This is controversial. RTOG 9704 randomized R0 and R1 PCA pts to CI 5-FU (250 mg/m2/d) CRT (50.4 Gy) and pre- and post-CRT with either additional 5-FU or gemcitabine. Among all eligible pts, there were no
differences. In a preplanned subset analysis of pts with pancreatic head tumors, trends favored gemcitabine: MS was 20.5 mos vs. 16.7 mos, and 3-yr OS was 31% vs. 22%, but results were NSS (p = 0.09). The 3-yr LR was significantly better for the gemcitabine arm (23% vs. 28%). Updated 2012
results showed significantly worse survival in pts with CA 19-9 >90 U/mL, positive nodes, & RT quality assurance protocol deviations. (Regine W et al.,
JAMA 2008; Berger AC et al., IJROBP 2012)

Question 63

What is the Tx paradigm for borderline resectable PCA?

Answer 63

Borderline resectable PCA Tx paradigm: consider staging laparoscopy, stent
placement if jaundice, and neoadj chemo +/− CRT → resection.

Question 64

What neoadj regimen should be used for borderline resectable PCA?

Answer 64

There is no standard neoadj Tx for PCA. Use similar paradigms as for locally advanced cases: multi-agent chemo for at least 4 cycles f/b
consideration of fluoropyrimidine-based CRT, e.g., (1) gemcitabine/Abraxane or FOLFIRINOX (leucovorin, fluorouracil, irinotecan,
and oxaliplatin) +/− fluoropyrimidine-based chemo/RT, with RT to 45–50.4
Gy in 1.8–2 Gy/fx or 30 Gy in 3 Gy/fx per the MDACC paradigm. (Breslin TM et al., Ann Surg Oncol 2001)

Question 65

What is the Tx paradigm for locally advanced PCA?

Answer 65

Locally advanced unresectable PCA Tx paradigm: biliary stent (if jaundice) can be done 1st then based on KPS→ (1) induction chemo → restage →
CRT, (2) definitive CRT if not candidate for multi-agent chemo, or (3) chemo
alone. CRT regimens typically involve 5-FU or gemcitabine. Chemo alone or induction chemo involves gemcitabine (poor KPS or unable to tolerate
multiple agents), gemcitabine + Abraxane, FOLFIRINOX, or other
combination in clinical study. Multi-agent chemo is preferred, and 4–6 cycles
for induction chemo.

Question 66

What is the role of regional LN RT with neoadj or definitive CRT for borderline resectable or locally advanced PCA?

Answer 66

LN irradiation is controversial in the neoadj or definitive setting. In this
setting, some institutions trend toward using smaller fields that treat gross
tumor plus a small margin (McGinn CJ et al., JCO 2001), while others have
continued to treat LN in the definitive setting (Ben-Josef E et al., IJROBP 2004). Recent Alliance (A021501) & NRG (RTOG 1201) cooperative group clinical trial designs have not involved elective LN RTin the neoadj or definitive setting, respectively.

Question 67

What is the evidence to support induction chemo prior to CRT in locally
advanced PCA?

Answer 67

In a retrospective study of locally advanced PCA pts from MDACC, pts who
rcvd induction gemcitabine f/b CRT had longer MS than pts that had initial CRT (12 mos vs. 8 mos). They hypothesize that induction chemo may select for pts that benefit from CRT. (Krishnan S et al., Cancer 2007)

Question 68

What definitive CRT regimen should be used for locally advanced PCA?

Answer 68

Standard regimen for definitive CRT: 5-FU (CI 250 mg/m2/d) + RT, with RT
to 50–60 Gy in 1.8 Gy/fx or 30 Gy in 3 Gy/fx.

Question 69

What study established the role of definitive CRT vs. RT alone in locally advanced PCA? What were the study arms and survival outcomes?

Answer 69

The GITSG 9273 trial (pts enrolled in the 1970s). Arm 1: RT alone, splitcourse
60 Gy in 2 Gy/fx; arm 2: 5-FU + RT, split-course RT to 40 Gy in 2 Gy/fx; arm 3: 5-FU + RT, split-course RT to 60 Gy in 2 Gy/fx. All arms rcvd maintenance 5-FU × 2 yrs. MS favored the CRT arms: 5.3 mos (arm 1) vs.
9.7 mos (arm 2) vs. 9.3 mos (arm 3). 1-yr OS favored the CRT arms: 10% (arm 1) vs. 35% (arm 2) vs. 46% (arm 3). There were no statistical
differences b/t the CRT arms. (Moertel CG et al., Cancer 1981)

Question 70

What study suggests that gemcitabine alone may be sup to 5-FU–based
CRT in locally advanced PCA? What were the study arms and survival
outcomes?

Answer 70

FFCD/SFRO study (French). Arm 1: RT (60 Gy) + CI 5-FU + intermittent cisplatin → maintenance gemcitabine; arm 2: induction gemcitabine → maintenance gemcitabine. Upfront CRT was more toxic and had worse survival outcomes. MS was 8.6 mos vs. 13 mos, and 1-yr OS was 32% vs.
53%. Criticism: The upfront CRT was not standard and was very poorly tolerated. (Chauffert B et al., Ann Oncol 2008)

Question 71

What study suggests that concurrent gemcitabine-based CRT is sup to gemcitabine alone for locally advanced PCA?

Answer 71

ECOG 4201, which closed early d/t slow accrual. 74 pts (71 evaluable). Arm 1: gemcitabine alone; arm 2: gemcitabine + RT, then gemcitabine alone. MS
and 2-yr OS were better with CRT (11.1 mos vs. 9.2 mos and 12% vs. 4%, respectively). There were higher G4/5 toxicities with arm 2, but G3/4 toxicities were similar. (Loehrer PJ et al., JCO 2011)

Question 72

What were the trial design, findings, and criticisms of the recent trial, LAP-07, regarding Tx for locally advanced PCA?

Answer 72

442 pts underwent 4 cycles of induction chemo w/ gemcitabine +/– erlotinib f/b continued gem or RT+cape 800 mg bid. RT involved 54
Gy/30 fx w/o prophylactic nodal irradiation. Erlotinib had trend to poorer survival (HR 1.19, p = 0.09). Only ∼1/2 of pts underwent 2nd randomization. MS did not differ b/t the CRT (15.2 mos) vs. chemo (16.5 mos) groups
(NSS). CRT associated with decreased with LRF (32% vs. 46%, p = 0.03) but increased DM (60% vs. 44%, p = 0.04). Toxicities were similar (except worse nausea with CRT), and there was increased time off therapy for the CRT group (6.1 vs. 3.7 mos, p = 0.02) (Hammel P et al., JAMA 2016).

Criticism: use of single-agent chemo in the induction arm. Of note, QA revealed 68% RT plans had minor or major deviations, and 9% of pts
randomized to CRT never rcvd RT.

Question 73

What 2 regimens may have greater activity than gemcitabine alone in
metastatic PCA?

Answer 73

FOLFIRINOX and gemcitabine + Abraxane both were sup to gemcitabine alone in 2 separate phase III RCTs in metastatic PCA. In a French study of 342 pts, FOLFIRINOX had an MS of 11.1 mos vs. 6.8 mos for gemcitabine and increased QOL despite increased G3/4 toxicities (Conroy T et al., NEJM 2011). The MPACT international study of 861 pts showed gemcitabine +
Abraxane had MS of 8.5 mos vs. 6.7 mos for gemcitabine alone. (Von Hoff DD et al., NEJM 2013)

Question 74

Estimate the MS and 1-yr OS for pts with locally advanced PCA at Dx, based on LAP-07.

Answer 74

Outcomes for locally advanced PCA: MS was ∼13 mos and 1-yr OS was ∼50% based on LAP-07.

Question 75

In PCA pts, what are 3 Tx options for tumor-associated biliary obstruction?

Answer 75

Tx options for tumor-associated biliary obstruction:

1. Endoscopic biliary stent
2. Percutaneous biliary drainage with subsequent internalization
3. Open biliary-enteric bypass

Question 76

In PCA pts, what are 3 Tx options for tumor-associated gastric outlet obstruction?

Answer 76

Tx options for tumor-associated outlet obstruction:

1. Gastrojejunostomy
2. Enteral stent
3. PEG tube

Question 77

In PCA pts, what Tx should be considered for tumor-associated severe abdominal pain refractory to analgesic med?

Answer 77

Celiac plexus neurolysis is an effective option for Tx-refractory pain.
Radiation

Question 78

Are there any data on stereotactic body radiotherapy (SBRT) for
pancreatic cancer?

Answer 78

Several studies have evaluated SBRT for unresectable PCA. Early reports suggest excellent LC; however, a significant proportion of pts experience duodenal toxicity

Stanford (Chang DT et al., Cancer 2009): 77 pts with unresectable PCA rcvd
25 Gy × 1 with CyberKnife SBRT. The 6- and 12-mo isolated LR rate was 5% and 5%, respectively. The PFS at 6 and 12 mos were 26% and 9%, respectively. The 1-yr OS was 21%. At 12 mos, the ≥G2 late toxicity was 25%, including 1 small bowel perforation (G4), 1 duodenal stricture (G3), and 3 gastric ulcers (G3).

Beth Israel Deaconess (Mahadevan A et al., IJROBP 2010): 36 pts with
unresectable PCA rcvd 24–36 Gy CyberKnife SBRT in 3 fx. Gemcitabine was given after SBRT. LC rate was 78%, and MS was 14.3 mos. 39% developed ≥G2 toxicity (25% G2, 14% G3); including 3 pts with vomiting and dehydration (G3) and 2 pts with GI bleed (G3).

John Hopkins, MSKCC, Stanford (Herman J et al., Cancer 2014) 49 pts, rcvd 1 cycle gemcitabine, then 33 Gy in 5 fx, with 1-yr freedom from local progression (FFLP) 78%, MS 13.9 mos, with 11% grade 2 or more toxicity, 1 G5 GI bleed, 1 G3 bleed, 1 G3 ulcer.

Question 79

Is there a potential for dose escalation with the use of IMRT in pancreatic
cancer?

Answer 79

Yes. A phase I–II trial of IMRT dose-escalation (50–60 Gy) with concurrent gemcitabine in 50 pts with unresectable PCA found dose-limiting toxicities in 11 pts, including duodenal bleed (3 pts) and perforation (1 pt). The
recommended dose was 55 Gy, with an estimated 24% rate of dose-limiting toxicity (Ben-Josef E et al., IJROBP 2012). Single institution data from MDACC (Krishnan S et al., IJROBP 2016) found improved survival (MS
17.8 vs. 15 mos, p = 0.03) in pts with BED >70 Gy10 compared to biological effective dose (BED) ≤70 Gy10. No increased toxicity was seen in the higher-dose group. An example of BED 70 Gy10 would be 57.27 Gy in 25 fx.

Question 80

Do Tx paradigms differ b/t pancreatic and periampullary adenocarcinoma?

Answer 80

Yes. Tx paradigms can differ b/t pancreatic vs. periampullary cancers.
Consider observation for completely resected T1–T2, N0 ampulla of Vater carcinoma. Retrospective reviews suggest high OS (5-yr OS ∼80%) with observation alone (Willett C et al., Surg Gynecol Obstet 1993). Otherwise, periampullary adenocarcinoma generally follows PCA paradigms, especially for T3–T4, poor histologic grade, LVSI/PNI (Krishnan S et al., IJROBP
2008), or node+ pts. (Zhou J et al., Radiother Oncol 2009)

Question 81

What are the expected acute and late RT toxicities associated with Tx of
resected and unresectable PCA?

Answer 81

Acute toxicities: nausea, diarrhea, small bowel obstruction, weight loss, anorexia, abdominal pain
Late toxicities: small bowel obstruction/stenosis/perforation, gastric/small bowel ulceration and/or bleeding, biliary stenosis obstruction, 2nd malignancies

Question 82

What are duodenal toxicities related to fractionated RT or SBRT for PCA?

Answer 82

RT can induce duodenal injury: ulceration, bleeding, perforation, and fistula
formation. These mostly occur in the 1st 12 mos after completing RT.

Question 83

What is the typical f/u schedule after Tx of pancreatic cancer?

Answer 83

Pancreatic cancer f/u schedule after Tx: surveillance q3–6mos × 2 yrs, then q6–12mos. At each visit, perform full H&P for Sx assessment, and consider
CA 19-9 levels, LFTs, and abdominal CT with contrast.