management of pancreatic cancer

1. PANCREATIC CANCER
MANAGEMENT
Dr. Mohamed Salat Gonjobe
4TH semester.
FACILITATOR: Dr NDUMBALO
1

2. OUTLINE
I. INTRODUCTION
II. CASE PRESENTATION
III. Management of pancreatic cancer
resactable
Boderline
Unresectable
iv. Radiation techniques
v. CASE REVIEW
vi. Back to case

3. INTRODUCTION
 Pancreatic cancer is one of the leading cause of cancer-related
mortality world wide
 At diagnosis, 52% of all patients have distant mets and 26% have
regional spread.
 Cancers arise from both the endocrine and exocrine portions of
the organ, although 95% arise from the exocrine part.
 Approximately 75% of all pancreatic carcinomas occur within the
head and neck of pancreas, 15-20% body and 5-10% in the tail.
 …
Peritoneal and liver mets are most common. Lung is most
common location outside the abdomen.
 Surgical excision is the definitive RX with a 5-yr survival rate (after
resection) of ∼20%, but its only possible in 15%–20% of the pts
 Overall, PC carries an unfavorable prognosis. For all stages
combined, the 1- & 5-year survival rates are 24% & 5%,
respectively…
…

4. Case Presentation
 Name: A. K.H
 Age: 71yrs female
 Mikocheni, Dar es salaam
 Marital status: Married
 Religion: Christian
 Occupation: peasant
 Presenting complaint;
abdominal pains for 4 months
weight loss for 3 months

5. History of presenting illness
 Patient presented with history of abdominal pains 4 months and
weightloss for 3 months,pain is persistent and radiating to the back.
it was associated with abdominal fullness and lack of appetite with
on and off nausea.the symptoms were agrevated by feeding and
relieve a bit with some painkillers.no history of vomiting,diarrhea
constipation or itchness reported.
 ROS..normal
 PMSH..known DM patient on management,no hx of hypertension
or allergy.no hx of transfusion nor surgery.
 Had history of cigarrete smoking and alcohol intake although she
reported to have stopped

6. Cont; of HPI
 O/E sicklooking patient Cachexic KPS 80, no jaundice no
pallor,no cyanosis
 GIT EXAM..mild distension in epigastric region,tender on
palation,mass noted in the epigastric region 3 by 3 cm,.
 Labworks Fbp-normal findings
LFT—within normal ranges
RFT normal
 CA 19-9….75.81 ng/ml (normal 0-37)
 Imaging. CXR normal
CT scan chest normal
 CT SCAN ABDOMEN –heterogenous enhancing soft tissue mass
lesion approximately more than 4.41 by 6.38 by 6.94 noted in the
region of pancreatic body and involving peripancreatic vessels
and peritoneal lymphadenopathies noted.

7. summary
 A.K.H A 71 year old female who presented with history of
abdominal pains and weightloss for 4 months, it was associated
with abdominal fullness and lack of appetite with on and off
nausea. She is a known DM patient on management. O/E sick
looking patient Cachexic KPS 80 .GIT examination, Mild distension
in epigastric region with a mass noted measuring 3 by 3 cm
tender on palation. LABWORKS, CA19-9 was elevated 75.81 .CT
SCAN ABDOMEN heterogenous enhancing soft tissue mass lesion
approximately more than 4.41 by 6.38 by 6.94 noted in the region
of pancreatic body and involving peripancreatic vessels and
peritoneal lymphadenopathies noted. CT chest normal.patient
stage 3 (T4 N1 M0) locally advanced unresectable pancreatic
cancer

8. TREATMENT MODALITIES
 Surgery
 Chemotherapy
 Radiation therapy
 Targeted therapy

9. Management of pancreatic
cancer

11. Management of resectable PC
Surgery is the primary mode of treatment for PC.
Indications: T1 , T2 , rarely T3
1) SURGICAL OPTIONS:
 Pancreaticoduodenectomy (whipples procedure) with /
without sparing of the pylorus.
 Total pancreatectomy.
 Distal pancreatectomy.

12. CRITERIA DEFINING
RESECTABILITY STATUS
 No distant metastases
 No arterial tumor contact (celiac axis [CA], superior mesenteric
artery [SMA], or common hepatic artery [CHA])
 No tumor contact with the superior mesenteric vein (SMV) or
portal vein (PV) or ≤180-degree contact without vein contour
irregularity

13. Surgery
 WHIPPLE’S PROCEDURE (Pancreatico – duodenectomy)
 Includes en bloc resection of the duodenum, head of the
pancreas, immediate peripancreatic nodal tissue, and the
pylorus and antrum of the stomach.

15. Cont; surgery
➢ Total panceatectomy
 If cancer diffusely involves the pancrease or is present in
multiple sites within the pancrease
 It involves removal of entire pancrease,part of small intestine,
a portion of stomach the common bile duct, the gallbladder,
the spleen and the nearby lymph nodes.
➢ Body/tail cancers should undergo distal pancreatectomy
often with en bloc splenectomy

16. Cont; surgery
 In the past total pancreatectomy was advocated as better
procedure, but has not shown to improve survival compared to more
limited pancreaticoduedenectomy and it results in excrocrine
insufficiency and DM which are difficult to manage.
Lymph nodes Dissection:
 A standard lymphadenectomy in patients undergoing
pancreaticoduodenectomy entails removal of nodes at the
duodenum and pancreas, on the right side of the hepatoduodenal
ligament, the right side of the SMA the anterior and posterior
pancreaticoduodenal lymphnodes.
 data suggest that 12 to 15 lymph nodes constitute an adequate
assessment.

17. Cont; surgery
 Ultimately, prognosis for PC remains poor, even after potentially
curative Surgery in appropriately selected pts.
 Five-year actuarial survival rates ranges from 10.5% to 25% and
median survivals between 10.5 and 20 months
 Significant predictors of a better outcome
• Tumor size <3 cm
• Absence of lymph node metastases
• Negative resection margins
• Well-differentiated tumors

18. ADJUVANT THERAPY
 Single agent chemo alone/ Chemo-RT are both accepted.
 ChemoRT may be considered in patients with no
preoperative therapy who had either R1 resection or node-
positive disease after 4–6 mo of systemic chemo.
 ChemoRT may be with concurrent 5-FU, capecitabine, or
gemcitabine and may be delivered immediately,
sandwiched between chemo cycles, or after 2–6 cycles of
chemo

19. Cont; adjuvant therapy
 ASCO guideline Recommends 6-month adjuvant chemo for all
eligible patients who did not receive preoperative therapy
 If single agent is used , Gemcitabine is preferred to infusional 5-FU.
 If Chemo-RT is planned
• Gemcitabine 1000 mg/m2 Day 1, 8, 15
• Followed by Infusional 5FU + RT
5FU give 250 mg/m2 C-IV daily with RT – 50.4 Gy/1.8Gy/28 #s.
• Followed by Gemcitabine (same dose) every 4 weeks for 3 – 5
cycles.

20. NCCN POST OPERATIVE ADJUVANT
THERAPY

21.  phase 3, open-label, multicentre, randomised clinical trial at 92
hospitals in Europe.
 Eligible patients were aged 18 years or older and had undergone
complete macroscopic resection for ductal adenocarcinoma of
the pancreas (R0 or R1 resection).
 Pt randomized into two arms within 12 weeks of surgery to receive
six cycles of either 1000 mg/m2 gemcitabine alone administered
once a week for three of every 4 weeks (one cycle) or with 1660
mg/m2 oral capecitabine administered for 21 days followed by 7
days' rest (one cycle).
 The primary endpoint was overall survival, measured as the time
from randomisation until death from any cause

22.  Of 732 patients enrolled, 730 were included in the final analysis. Of
these, 366 were randomly assigned to receive gemcitabine and
364 to gemcitabine plus capecitabine.
 The median OS for patients in the gemcitabine plus capecitabine
group was 28,0 months (95% CI 23·5-31·5) compared with 25.5
months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82
[95% CI 0·68-0·98], p=0.032)
 CONCLUSION: The adjuvant combination of gemcitabine and
capecitabine should be standard of care following resection for
pancreatic ductal adenocarcinoma.

23. IS THERE A ROLE OF
RT?

24.  Systematic review and meta-analysis of 5 RT (GITSG, Norway,
EORTC, Japan, ESPAC-1) of adjuvant CHT and chemoRT for 1,136
patients
 CHT showed reduction in risk of death by 25% (HR 0.75, CI: 0.64–
0.90, p = .001) and improved MS at 19 months versus 13.5 months
without CHT.
 No significant difference in risk of death with chemoRT (HR 1.09,
CI: 0.89–1.32, p = .43)
 Subgroup analysis showed chemoRT IS more effective with
positive margins.

25. Conclusion: CHT is effective adjuvant therapy while
chemoRT is not unless pt has margin-positive disease.

26. PROSPECTIVE, RANDOMIZED TRIALS FOR
ADJUVANT THERAPY

27. Management of borderline PC
Boderline tumors are defined as those that abut the superior
mesenteric artery,Abut or encase the common hepatic artery
over a short segment or occlude the superior mesenteric vein or
portal vein.
 Tumours are considered resectable upon good response to
neoadjuvant RX including induction chemotherapy,
preoperative chemoradiation or a combination of both.
 While the heterogeneity of the trials on neoadjuvant therapy
in borderline resectable PC limits the power of any
conclusion, many individual series demonstrate improved R0
resection and promising survival rates.

28. Potential benefits of Neoadjuvant
therapy
 Downsize borderline resectable tumors to resectable;
 Increase likelihood of R0 resection in resectable patients; increase
proportion of resectable patients who will receive chemo and/or
RT;
 Help to Select patients with stable or disease responsive to therapy

29. Cont;
 Recent chemotherapy regimens, such as FOLFIRINOX [folinic
acid (leucovorin)/5-FU/irinotecan/ oxaliplatin], have already
shown promising results in small series of pts with borderline
resectable lesions (30%–45%).
 This Pts should be included in clinical trials wherever possible.
 In routine practice, if the pt is not included in a trial, a period of
chemotherapy (gemcitabine or FOLFIRINOX) followed by
chemoradiation and then surgery appears to be the best option.

30. Management of
unressectable pancreatic
tumor

31. UNRESECTABLE PC
 Unresectable disease is usually characterized by one or more of
the following features:
(1) Distant metastasis or extensive peripancreatic lymph node
involvement,
(2) Encasement or occlusion of the SMV or SMV/portal
confluence,
(3) Direct involvement of the SMA, inferior vena cava, aorta, or
celiac axis

32. Locally advanced disease
 When the pt has no metastases and the tumour is not
considered as borderline resectable, the tumour is defined as
truly locally advanced .
 Treatment of this group of pts remains highly controversial.
Regardless of many RX strategies, the average OS for these pts
remains low (<2 year) in most studies.

33. NCCN GUIDELINES FOR LOCALLY ADVANCED

34. Chemotherapy or
radiotherapy for LAPC?

35.  An international, open-label, phase 3 randomized trial, where 449 patients
were enrolled between 2008 and 2011. Follow-up ended in February 2013.
 OBJECTIEVS To assess whether chemoradiotherapy improves overall survival
of patients with locally advanced pancreatic cancer controlled after 4
months of gemcitabine-based induction chemotherapy and to assess the
effect of erlotinib on survival.

37. CONCLUSION
 There was no significant difference in overall survival with
chemoradiotherapy compared with chemotherapy alone and
there was no significant difference in overall survival with
gemcitabine compared with gemcitabine plus erlotinib used as
maintenance therapy
 Thus, the standard of care for these pts currently remains as 6
months of gemcitabine.

38. Advanced/metastasis
 The primary goal of treatment for metastaic pancreatic ca is
palliation and lengthening survival. survival benefits are usually
limited to patient with adequate performance status with good
pain management,patient biliary stent and adequate nutrition
intake,
 Systemic therapy is therefore recommended for patient with
metastatic disease and good performance status

39. NCCN GUIDELINE METASTATIC DSE

40.  Randomized prospective study 342 patients.followed up
for six months
 This trial included pts who were selected based on their
ability to receive aggressive chemotherapy ECOG status
0 or 1
 The median OS was 11.1 months in the FOLFIRINOX group
compared with 6.8 months in the gemcitabine group [HR
for death, 0.57; 95% CI 0.45–0.73; P < 0.001). More adverse
events were noted in the FOLFIRINOX group
 Conclusions: As compared with gemcitabine, FOLFIRINOX
was associated with a survival advantage and had
increased toxicity. FOLFIRINOX is an option for the
treatment of patients with metastatic pancreatic cancer
and good performance status

41. Targeted Therapeutic Agents
in Pancreatic Cancer
Poor results with conventional chemotherapy have led to ongoing
development of novel agents against PC. These new agents are designed
to target specific cellular pathways involved in tumor progression.
• Examples include inhibitors of farnesyltransferase, epidermal growth
factor receptor, and matrix metalloproteinases.
• These new biological agents show impressive results in both in vitro and
animal studies.
• However, efficacy in human trials has been more difficult to
demonstrate.

42. Radiation Approaches:
 RT and CRT are sometimes used for PC in the resectable and
adjuvant setting because they reduce likelihood of local
recurrence.
 The major goal of RT is to:
a) Sterilize vessel margins and increase the likelihood of margin-
negative resection.
b) Enhance local control and prevent d’se progression.
 Options include;
a) 45-54gy in 1.8-2.5 Gy fractions (doses higher than 54 Gy may be
considered if clinically appropriate)
b) OR 36 Gy in 2.4 Gy fractions

43. Field borders (AP/PA fields)
 Head of Pancreas lesions
• Superior border – Upper border of
T11
• Inferior border – Lower border of
L3
• Right border – Extended to cover
the duodenum and porta hepatis
• Left border – 2 cm to the left from
left edge of vertebral body

44. Field borders (AP/PA fields)
 Body of Pancreas lesions
• Superior border – Above
T11
• Inferior border – Lower
border of L3
• Right border – 2 cm to the right
from the right vertebral body edge
• Left border – Extend to
include the splenic hilum

45. Field borders (Lateral fields)
 Anterior : 1.5 – 2 cm
anterior to the tumour
 Posterior : 1.5 cm
behind the anterior portion of the
vertebral body
 Superior : Upper border
of T11
 • Inferior: Lower border of L3

46. Radiotherapy technique 3D
Conformal or IMRT
Immobilisation
 The patient lies supine with arms above the head in arm rests
 CT scans are acquired with a slice thickness of at 2–5mm
 interslice intervals from the top of the liver or top of T11 to cover
lymph nodes to the lower border of L3 and/or kidneys.

47. Cont;
 CT-MRI fusion may be appropriate in some cases if additional
information is derived from an MR scan
 Renal contrast is given and an initial anteriorposterior (AP) and
lateral films are taken to establish the position of the kidneys.
 oral contrast is given to visualize the stomach and duodenal C-
loop, which will localize the position of the head of the
pancreas

48. Target volume deliniation
 For lesions of the head of the pancreas,
invade the medial wall of the duodenum, and therefore the
entire involved duodenal wall should be covered for lesions
nodal groups should include the pancreaticoduodenal,
suprapancreatic, celiac, and porta hepatis lymph nodes.
 For lesions in the pancreatic body or tail
the target volume includes the tumor with a 2- to 3-cm margin
pancreaticoduodenal and porta hepatis nodes, lateral
suprapancreatic nodes, and nodes of the splenic hilum.

49. Target Volume Deliniation
 GTV which includes any enlarged regional lymph nodes of 1.5
cm (GTV-T and -N)
 The CTV should include visible tumour and surrounding oedema
 PTV margins are anisotropic with 5–10 mm in the AP direction,
2–4 mm in the transverse plane
 15–30 mm cranio-caudally to take account of organ movement
with respiration or gut motion

50. 67 yo F with resectable pancreatic adenocarcinoma s/p Whipple c/w
stage IIB (pT3N1M0) with +mgn
She received concurrent chemorad, 50.4Gy in 28 fractions to the post-
operative bed as well as peripancreatic, celiac, superior mesenteric,
porta hepatis, and para-aortic nodes.

51.  TECHNIQUE: She was treated with adjuvant chemoradiation
using IMRT and concurrent Xeloda. This was only after 6 months
of post-operative gemcitabine and a restaging scan that did
not show metastatic disease.

52. DOSE CONSTRAINTS

53. Palliative and supportive care
 Before even considering systemic chemotherapy, pts with
metastatic PC may need interventions to provide relief of biliary
and/or duodenal obstruction, malnutrition, and pain.
 Relief of jaundice can be achieved by biliary stents placed
percutaneously or endoscopically. Because these procedures are
usually well tolerated and perfomed on an outpatient basis, they
have become increasingly popular in the MX of malignant biliary
obstruction.
 Several randomized trials have demonstrated no difference in
survival between pts palliated endoscopically versus surgically for
obstructive jaundice

54. pain
 Pain in PC can be extremely distressing and may respond poorly
to oral narcotics.
 Percutaneous or surgical chemical neurolysis with alcohol is an
alternative palliative measure that can help in controlling pain or
decreasing narcotic use. Randomized trials have shown that
neurolysis of the celiac ganglion can offer relief to many pts.
 Lastly, radiation therapy may also be used for pain MX in selected
pts.

55. Cancer cachexia
 Cancer cachexia is a universal feature of advanced PC. The majority
of weight loss is secondary to the still poorly understood paraneoplastic
effects of the tumor on metabolism and calorie utilization.
 Agents targeting various cytokines such as interleukin-1α (IL-1α),
thought to contribute to cachexia are now being evaluated.
 Pancreatic exocrine insufficiency is a result of the loss of pancreatic
parenchyma, pancreatic ductal obstruction, decreased pancreatic
stimulation, or acid-medicated inactivation of pancreatic enzymes.
Clinical manifestations are abdominal cramps, bloating, steatorrhea,
and malnutrition with resultant weight loss.
 Oral administration of exogenous pancreatic enzymes is considered
standard therapy

56. Back to the case
 A.K.H A 71 year old female who presented with history of
abdominal pains and weightloss for 4 months, it was
associated with abdominal fullness and lack of appetite with
on and off nausea. She is a known DM patient on
management. O/E sicklooking patient Cachexic KPS 80 .GIT
EXAM..mild distension in epigastric region with a mass noted
measuring 3 by 3 cm tender on palation. LABWORKS, CA19-9
was elevated 75.81 . CT scan-heterogenous enhancing soft
tissue mass lesion approximately more than 4.41 by 6.38 by
6.94 noted in the region of pancreatic body and body
involving peripancreatic vessels and peritoneal
lymphadenopathies noted.chest CT normal.patient stage 3
(T4 N1 M0) locally advanced unresectable pancreatic
cancer.
 Pt got gemcitabine monotherapy and analgesics.got 6
cycles of chemo so far and is due for first followup on 2nd sept
2021.

57. Take home message
 Resection remains the only chance for a cure for pancreatic
adenocarcinoma followed by adjuvant therapy.
 Boderline resectable patients and select resectable patient
can undergo neoadjuvant therapy .
 Patient with locally advanced unresectable disease and good
performance status can undergo chemotherapy and
chemoradiaton with second line therapy if performance status
is maintained after progression.
 Good performance status patient presenting with metastatic
disease can undergo chemotherapy and can undergo
second line therapy if performance is maintained after
progression

58.  Specific palliative measures are recommended for patient with
advanced PC characterized by biliary or gastric obstruction. Severe
abdominal pain, or other tumor associated manifestation of the
disease

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