about the diagnosis and treatment of pancreatic cancer

1. CHEMOTHERAPY AND RADIOTHERAPY
IN
PANCREATIC CANCER
PRESENTER- Dr HARDIK
SHARMA
MODERATOR- Dr SHIKHA
GOYAL

2. INTRODUCTION - EPIDEMIOLOGY
• The Majority of cases are locoregionally advanced and only 15 to 20 percent are potentially
resectable at presentation , usually because of vascular invasion
• Majority of these tumors (85%) are adenocarcinomas arising from the ductal epithelium
• Defining the treatment strategy for patients suffering from pancreatic cancer requires a
specialised multidisciplinary team that includes: surgeons, radiation oncologist, medical
oncologist, gastroenterologists, and supportive palliative care specialists.
• Majority of patients with pancreatic cancer progress to either metastatic or locally advanced
disease in the asymptomatic phase
• BRCA 2 gene frequency ass with pancreatic ca (70%) & more sensitive to platinum agents
2

3. ANATOMY
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• Pancreas lies in the retroperitoneal space of the
upper abdomen
• It is partly exocrine and partly endocrine
• Exocrine part secretes the digestive pancreatic
juice, and the endocrine part secretes hormones,
eg. Insulin, glucagon
• Pancreas is “J”-shaped or retort shaped set
obliquely
• Length: 12–15 cm
• Width: 3–4 cm
• Thickness: 1.5–2 cm
• Weight: 80–90 g

4. BLOOD SUPPLY
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5. LYMPHATIC DRAINAGE
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• Rich lymphatic drainage of the pancreas is
interconnected with duodenal lymphatics
• The pancreatic head drains to
• The pancreatic body and tail drains to
Peripancreatic, common hepatic
nodes, hepatoduodenal nodes, SMA
nodes, celiac nodes, ant & post
pancreaticoduodenal nodes
splenic artery, peripancreatic, celiac,
superior mesenteric, paraaortic nodal
stations, splenic hilum

6. CLASSIFICATION
ENDOCRINE NEOPLASMS
• INSULINOMA
• GLUCOGONOMAS
• GASTRINOMAS
• SOMATOSTATATINOMAS
• VIPOMA
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NON-ENDOCRINE NEOPLASMS
• DUCTAL ADENOCA- 85-90%
• IPMN WITH ASS INV CA
• MCN WITH ASS INV CA
• SOLID PSEUDOPAPILLARY
• ACINAR CELL CA
• PANCREATOBLASTOMA
• SEROUS
CYSTADENOCARCINOMA

7. CLINICAL PRESENTATION
SYMPTOMS
• Asthenia- 86%
• Weight loss-85%
• Anorexia- 83%
• Abdominal pain-79%
• Epigastric pain-71%
• Dark urine-59%
• Jaundice -56%
• Nausea- 51%
• Back pain- 49%
• Diarrhoea- 44%
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SIGNS
• Jaundice
• Hepatomegaly
• Right upper quadrant mass
• Cachexia
• Courvoisier’s sign
• Ascites
More common
in head region
(60-70%)
Body & tail
region cause
late symptoms
(20-25%)

8. SPREAD
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Routes Descriptions
Local
extension
• Involvment liver, duodenum & blood vessels like celiac axis, SMA
from tumours of pancreatic head or body is common
• Body/tail tumour extension on stomach, intestine, and spleen and
obstruction of bile duct is relatively uncommon
• 90% have PNI; peritoneal seeding is common, even in resectable
disease
Regional
lymph node
metastasis
• lymph node involvement – 75% at diagnosis
• Lymphatic drainage depends on origin of primary disease
Distant
metastasis
• liver, peritoneum and lung
• To other organs are uncommon

9. DIAGNOSTIC ALGORITHM
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AST, ALT, S. BILIRUBIN,
S. AMYLASE, S.
LIPASE

10. DIAGNOSTIC ALGORITHM
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11. PANCREATIC TRIPLE PHASE MDCT
• The typical CT appearance of an exocrine
pancreatic cancer is an ill-defined
hypoattenuating mass within the pancreas
• Dilatation of both pancreatic duct & bile duct,
commonly referred as the “ double duct sign” is
present in 62-77% of cases of pancreatic
cancer.
• Sensitivity of CT for pancreatic cancer is
highest (88-97%) with triple phase MDCT
• Sensitivity for hepatic metastases is high,
particularly using the pancreatic protocol
technique 20XX Pitch Deck 15

12. PANCREATIC CT
• Arterial phase of enhancement- corresponds to the first 30 sec after the start of the
contrast injection, provides excellent opacification of celiac axis, SMA and
peripancreatic arteries.
• Pancreatic phase- obtained at 30-45 sec, an attenuation diff between tumor and
normal pancreas, which increases lesion prominent, is best achieved after peak
enhancement of the aorta in the arterial phase but before peak enhancement of the
liver, which occurs in the portal venous phase
• Portal venous phase - obtained at 60 to 70 sec after the start of the contrast injection,
provides better enhancement of the SMV, splenic and portal veins. In addition, peak
hepatic enhancement, which optimizes the detection of hepatic metastases, also
occurs in the portal venous phase
16

13. PANCREATIC CT
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14. CT – GRADING SYSTEM FOR PREDICTING VASCULAR
INVASION
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GRADING DEGREE OF INVOLVMENT (
CIRCUMFERENCE)
PERCENTAGE VASCULAR INVASION
0 NO CONTIGUITY/INVOLVEMENT 0 % OF CASES
1 <25% OF A VESSEL 0% OF CASES
2 25-50% OF A VESSEL 57% OF CASES
3 50-75% OF A VESSEL 88% OF CASES
4 >75% OF A VESSEL IN ALL CASES
a) ERCP-a malignant tumor of HOP with superimpose strictures, duct stricture in
excess of 1cm length
b) MRCP-It is at least as sensitive as ERCP in detecting pancreatic ca
c) EUS-EUS is not recommended as a routine staging tool
d) PET-CT

15. PET-CT
• One possible benefit of PET is enhanced detection of
small volume metastatic disease which is often missed
by CT.
• But the consensus-based guidelines for staging cancer
from the NCCN and ESMO do not recommend routine
use of PET/CT for staging of pancreatic cancer
• May be considered after formal pancreatic CT protocol
in high risk patients to detect extra-pancreatic
metastasis
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16. AJCC- STAGING OF PANCREATIC CANCER (8TH
EDITION)
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17. STAGING
• Five year survival rates stratified according
to stage grouping as follows
Stage IA- 39%
Stage IB- 34%
Stage IIA- 34%
 Stage IIB-28%
Stage III- 11%
Stage IV- 4.5%
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18. MANAGMENT
• RESECTABLE
• BORDERLINE RESECTABLE
• UNRESECTABLE BUT NOT
METASTATIC
• METASTATIC
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19. FACTORS IMPORTANT FOR DECIDING THERAPY
• After the staging of the tumour , patient will receive surgery/chemotherapy
or chemoradiotherapy
• But we have to see other parameter also to decide the which chemotherapy
will be suitable for the patient i.e.
1. Comorbidity score
2. Performance status
3. Serum bilirubin
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20. 20XX Pitch Deck 24
CRITERIA DEFINING RESECTABILITY STATUS

21. 20XX Pitch Deck 25

22. 20XX 26
RESECTABLE
PANCREATIC
CANCER
Surgery /
neoadjuvant therapy
If >T1No then
adjuvant therapy and
if T0 then
observation
Chemotherapy /
chemoradiotherapy
BRPC
Neoadjuvant therapy
Surgery
If >T1N0 then
adjuvant therapy and
if T0 then
observation
LAPC
Neoadjuvant therapy
(NACRT
/NACT/SBRT)
If become resectable
then surgery / if
remain unresectable
Chemotherapy /
chemoradiotherapy
Systemic therapy
(Chemotherapy +
immunotherapy)
PALLIATIVE
RADIOTHERAPY
SUPPORTIVE
CARE
METASTATIC
PANCREATC
CANCER
If unresectable then
systemic/ local
therapy
I

23. RESECTABLE DISEASE
• Surgical resection is the only potentially curative treatment for exocrine pancreatic cancer
• Because of the late presentation of the disease, only 15-20% of patients are candidates
for pancreatectomy
• Local unresectability is usually due to vascular invasion
• Prognosis of pancreatic cancer is poor even in those with potentially resectable disease
(R0)
• 5-year survival following surgery is only approximately 25 to 30% for node -ve and 10%
for node +ve tumors
• Patients who present with LAPC have a median survival of 8 to 14 months
• Up to 60% of patients present with metastatic disease, which carries a shorter median
survival of 4 to 12 months. 20XX Pitch Deck 27

24. WHIPPLE SURGERY
28
DISTAL PANCREATECTOMY

25. PATHOLOGICAL ANALYSIS
• Tumour size
• Histological grade
• Tumour type
• Margins around vessels, posterior margin, bile duct, enteric ,
• LVSI
• PNI
• Regional lymph node
• additional findings like chronic pancreatitis 29

26. PATTERNS OF FAILURE
• Three major sites of disease relapse dominate: locoregional, peritoneal
cavity and liver
• High local failure rates of 50% to 86% despite resection because of:
 Frequent cancer invasion into retroperitoneal soft tissues
 High rates of lymphatic and perineural involvement
 Inability to achieve wide retroperitoneal soft tissue margins because of
anatomic constraints to wide posterior excision
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27. ADJUVANT THERAPY
• The guidelines recommend adjuvant chemotherapy for all patients with
resected ductal adeno ca who did not receive neoadjuvant chemotherapy
included those with resected T1N0 disease
• Timing and duration- 6 months of adjuvant chemotherapy, ideally started
within 8 weeks of surgery (ASCO guideline)
• Data from other analyses suggest that starting adjuvant chemo up to 12
weeks of surgery may also not compromise OS (ESPAC-3, NCDB analysis)
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28. CHEMOTHERAPY- REGIMEN FOR ADJUVANT
THERAPY
• mFOLFIRINOX/FOLFIRINOX
• GEMCITABINE + NAB-PACLITAXEL
• GEMCITABINE + CAPECITABINE
• GEMCITABINE
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After seeing the patient
PS, COMORBIDITY
SCORE & S. BILIRUBIN
LEVEL

29. TRIALS IN ADJUVANT THERAPY
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30. ESPAC-1 ADJUVANT CT VS NO CT
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Survival benefit –
median OS (19.7 vs 14
months) p <0.03
No survival difference
post op CRT vs no adj
CT
MEDIAN OS (15 VS 16
MONTHS)
Adjuvant chemotherapy has a
significant survival benefit,
whereas adjuvant
chemoradiotherapy has a
deleterious effect on survival.

31. FLAWS IN ESPAC-1 :
• Physicians were allowed to choose which of the three parallel trials to enroll
patients on, lead to bias
• Patients could receive background CRT or CT as decided by their physician
• The CRT group received RT in a split course fashion, and the final dose (
40-60 Gy) was left to the judgement of treating physician
• CRT group did not include post-RT adj chemotherapy
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32. CONKO-001 TRIAL
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3 & 5 year DFS (
23.5 vs 8.5%)
p<0.0.1
3 & 5 year OS (
36.5- vs 19.5%)
both favoured
GEM ARM
Adjuvant gemcitabine
chemotherapy has a
significant survival
benefit.

33. ESPAC -3 TRIAL
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Median OS GEM VS LV-
FU
Was similar (23.6 vs 23
months) p<0.4
Time to start CT ( 8 wks
vs later) was an imp
survival factor
Median OS was similar with
GEM vs LV-FU

34. RTOG 9704 STUDY
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No significant 5-year OS or
DFS between two groups
p<0.9
Better median OS (20.5 vs
17 months ) in head vs
body/tail site
No significant 5-year OS or
DFS between gem vs 5-FU
with CCT

35. ESPAC-4 TRIAL – GEM VS GEM-CAP
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Significant median OS
(30.2 vs 27.9) months
and fiver year OS (28
vs 17%) p<0.03
Grade ¾ toxicities more
in GEM+CAP VS GEM
alone arm
Adjuvant gemcitabine+
capecitabine chemotherapy
has a significant survival
benefit.

36. MODIFIED FOLFIRINOX – PRODIGE-24 TRIAL
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Median DFS (21.6 VS
12.8) months
Median overall survival
(54.4 vs 35 months)
More toxicity ass with
mFOLFIRINOX vs
GEMCITABINE

37. APACT TRIAL III- GEMCITABINE + NAB-PACLITAXEL
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2021. ESMO OS was
better (41.8 vs 37.7
months HR-0.88)
5-year OS ( 38% vs
31%)
DFS was not significant
(19.4 vs 18.8 months)
Adjuvant gemcitabine+ nab-
paclitaxel chemotherapy has
a significant survival benefit.

38. ADJUVANT CHEMORADIOTHERAPY
• Statistical data on chemoradiotherapy is still not clear
• For patients who received either gemcitabine alone or gem+ capecitabine for
adjuvant chemotherapy, addition to chemoradiotherapy to chemotherapy but
tolerability with FOLFIRINOX is unclear
• Chemotherapy alone as the preferred regimen for adjuvant therapy, but they
include induction chemotherapy for four to six months f/b CRT as an
acceptable option for adjuvant therapy
• Most European clinicians advocate chemotherapy alone, emphasizing the
O.S. of chemotherapy in German CONKO-001 trial, the lack of significant
benefit with CRT in EORTC and detrimental impact CRT on survival seen in
42

39. • On other hand, the American approach, which includes chemoradiotherapy in
addition to adjuvant chemotherapy, emphasizes the following points:
 The high risk of local failure after resection of pancreatic cancer and the potential for
benefit from chemoradiotherapy
 The high rate of positive retroperitoneal margins and the adverse impact of this
finding on survival
 The survival benefit form CRT in the GITSG study
 The trend toward improved survival seen with chemoradiotherapy on underpowered
EORTC study
 The serious flaws of the ESPAC-1 trial and the inherent difficulty in drawing
definitive conclusions from this study
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40. ADJUVANT CHEMORADIOTHERAPY TRIALS
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41. GITSG STUDY (1985)
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Median survival for obs vs
adj (10.9 vs 21 months
p(0.03)
2 year OS for obs vs CRT
( 15% vs 42%)
Adjuvant CRT has a
significant survival benefit vs
SURGERY + observation

42. GITSG TRIAL
• 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.
• EBRT approach in this trial was considered low dose with split-course
technique and use of large treatment fields
• Additionally, the inclusion of both CRT and adjuvant chemotherapy after
surgery evaluated two treatment variables, making it difficult to discern the
true effect of either treatment alone
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43. EORTC 40891 ( KLINKENBIJL ET AL 1999)
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no median survival
benefit with adj crt (17 vs
13 mnths)
FLAWS
• Split RT
• Dose suboptimal
• No prospective
assessment
Adjuvant CRT (5-FU) has a no
significant survival benefit vs
SURGERY + observation

44. HERMAN ET AL ( JOHN HOPKINS)
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Adjuvant CRT improved
survival among both margin
negative and margin-
positive patients
Limitation
Study does not showed as
whether CRT is superior to
chemotherapy alone
Adjuvant CRT has a
significant survival benefit vs
SURGERY + observation

45. DOES CRT ADD BENEFIT TO CT- EORTC 40013
PHASE II
• Beside the ESPAC-1 trial , the only trial to compare the relative benefits of
adding CRT to systemic therapy vs systemic therapy alone was EORTC
40013/FFCD 9203/GERCOR Phase II study
• In contrast to the results of ESPAC-1 , CRT was
not deleterious
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46. META-ANALYSIS
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CT with 5-FU or
GEM is optimum adj
treatment for
PANCREATIC CA
Reduces mortality
after surgery by about
a third
CRT plus CT is less
effective in prolonging
survival and is more
toxic than CT

47. OVERVIEW-BORDERLINE RESECTABLE DISEASE
• For fit patients, initial attempt at NAT f/b restaging and surgical exploration
rather than upfront surgery
• For most patients, an initial period of CT rather than immediate RT or CRT
• A careful assessment fir resectability should be undertaken after 4 to 6
months of NACT
• Rationale- major goal of surgery to get R0 resection ; because a margin
positive resection strongly predicts early recurrence and short survival
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48. BORDERLINE RESECTABLE DISEASE
• Chemoradiation (with 5FU-based chemo)
• SBRT/IORT
• EBRT with novel chemotherapeutic or targeted agents
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RATIONALE OF NEOADJUVANT THERAPY
• Improve the selection of patients for whom resection will not offer a survival
benefit(i.e. those who rapidly progress to metastatic disease during preoperative
therapy
• Increases rates of margin negative resection, which is the major goal of surgery
• Early treatment of micro-metastatic disease

49. NEED - NEOADJUVANT THERAPY
• Approximately 25% of patient do not receive adjuvant therapy in a timely
manner after surgery or did not receive it at all.
• With neoadjuvant therapy, 20% to 40% of patients will be spare the morbidity
of resection because their metastatic disease becomes clinically apparent
• Preoperatively therapy could theoretically be less toxic and more effective
• Patients with local and unresectable lesions may be able to downstages to
allow for surgical resection
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50. BENEFITS OF NEOADJUVANT THERAPY
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R0 resection was higher with
preop therapy
(71% vs 40%)
Median OS (16 vs 14.3
months) with better DFS
& locoregional free
interval

51. SEER DATABASE- 3855 RESECTABLE PANCREAS
CANCER
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52. MAYO CLINIC TRIAL (1960)
• The MAYO clinic undertook an early randomised trial in the 1960s
• 64 patients with locally unresectable pancreatic adenocarcinoma received
35 to 40 Gy of EBRT with concurrent FU vs THE SAME EBRT plus placebo
• A significant survival advantage was seen for patients receiving EBRT with
5-FU vs EBRT only ( 10.4 vs 6.3 months)
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53. OVERVIEW-UNRESECTABLE BUT NOT
METASTATIC
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54. • A careful assessment of resectability should be taken after 2 months of
neoadjuvant therapy. In the era prior to FOLFIRINOX and GEMCITABINE,
it was rare for tumours to be converted to resectable after gemcitabine or
CRT
• For patients who are not considered candidates for surgical exploration,
continued chemotherapy is preferred approach
• RT as a single modality could be considered to palliative pain for a patient
who is not considered a candidate for combined CRT due to medical
comorbidities and whose pain is not adequately controlled with narcotic
analgesics
• Another option is celiac plexus nerve block
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55. LOCALLY ADVANCED PANCREAS CARCINOMA
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56. GEMCITABINE COMBINATIONS- NEOLAP TRIAL
• 2019 ESMO congress, preliminary report
sequential FOLFIRINOX was not
significantly superior with regard
to surgical exploration or rate of
complete macroscopic resection
( R0 or R1) margins, 45 vs 31%,
odds ratio 0.54
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57. 20XX Pitch Deck 61
ESPAC-5F TRIAL
No significant in resection
rate for SUREGRY (62%) VS
NACT (55%), p < 0.66
Significant survival
advantage at 1 yr for NACT
(77%) VS SURGERY (42%)
FOLFIRINOX showed best
survival vs SURGERY(84%)
vs compared with GEMCAP
(79%) and CRT (64%)

58. MD ANDERSON SERIES
• MD ANDERSON CANCER CENTER, 285 received FOLFIRINOX and 200
received gemcitabine plus nabpaclitaxel as the first line regimen
• Partial response was more common with FOLFIRINOX
• 27% underwent pancreatectomy in FOLFIRINOX arm vs 16% in
gem+nabpacli arm
• OS was similar (21 vs 20 months)
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59. IS THERE BENEFIT TO CRT AFTER INITIAL CT
Three unresolved controversies that impact the decision to pursue CRT after initial CT
1. Efficacy of post-NACT imaging to determine feasibility of R0 resection
2. Ability of RT to improve the rate of R0 resection (vs R2).
3. Whether RT gives additional gain over CT in adjuvant , neoadjuvant or perioperative
settings for LAPC.
Unfortunately, the benefit of RT with LAPC, whether initially resectable or potentially
resectable, remains an unresolved issue
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60. LAP07 TRIAL- LAPC
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CRT was not superior vs Cont
CT ( median OS 15.2 vs 16.5
months) p <0.001
Local control was significantly
better in CRT group ( 32% vs
46%) with CT alone
The independent contribution of
RT and CRT to surgical
outcomes was not addressed
There was no significant difference in OS
with chemoradiotherapy compared with
chemotherapy alone and there was no
significant difference in OS with gem
compared with gem+erlotinib used as
maintenance therapy

61. ECOG TRIAL, LOEHRER 2011
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Median overall survival with
GEM VS GEM + XRT ( 9.2
VS 11.1 months) p- 0.17
Greater incidence of grades
4 and 5 toxicities (41% v 9%)
in CRT, but grades 3 and 4
toxicities combined were
similar (77% in gem alone v
79% CRT).

62. STEREOTACTIC BODY RADIATION THERAPY
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There are no phase-III studies for SBRT in
pancreatic cancer and no comparative studies
Herman et al- single arm trial
• A significant reduction in cancer related pain
• High rate of freedom from local progression
(78%)

63. SBRT- PHASE-II ALLIANCE A021501- BRPC
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Eight courses of preop
mFOLFIRINOX or seven
courses of mFOLFIRINOX f/b
SBRT ( 33Gy to 40Gy in five #)
or hypo-fractionated IGRT(25Gy
in 5#)
Complete resection (42 vs 25%)
, 18 month OS (67.9 vs 47.3%)
and median OS (31 vs 17.1)
months all favoured CT alone vs
CT f/b SBRT

64. ALLIANCE A021501
This trial is problematic from number of standpoints:
• As noted above this trial was not statistically powered to compare FOLFIRINOX
with or without RT
• There were imbalances in certain prognostic factors between two groups. As an
example, CA19-9 was higher in SBRT arm (260) vs (167)
• More patients in SBRT arm developed metastatic disease and therefore were not
attempted resection
• The timing of surgery was four to eight weeks , which may not have fulfilled for
maximal downstaging
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65. TELETHERAPY TECHNIQUES
• 2D/3DCRT/ IMRT
• SBRT
• Conventionally fractionated RT (25-30#), moderately hypo
fractionated (12-15#) and SBRT (3-12#) are treatment option in the
management of pancreatic cancer
• There is no data to confirm superiority of one approach to over the
other
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66. TARGET VOLUME DELINEATION
Target volume consists of:
• Primary tumour ( include possible infiltration
of adjacent structure or organs)
• Involved regional lymph nodes
• Possible regions of increased risk for
subclinical disease
• Information about tumour motion
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67. SIMULATION
• Immobilization- depending on the intended treatment technique
• For conventionally # RT, positioned supine with arms above the
head with red foot rest
• For SBRT, immobilisation device for high precision positioning
which may include abdominal compression
• Planning CT obtained in exhalation breath hold with iv contrast in
pancreatic phase (45sec) to define the GTV
• Additional scans can be taken in venous phase to allow easy
identification of vascular structure especially if elective nodal
irradiation is planned
• Minimum flow of 3ml/s and delays of roughly 25,40 and 70 s from
injection
• Slice thickness of 3mm or less
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68. MOTION ASSESSMENT & MANAGEMENT
• 4D-CT- motion detection during treatment planning is mandatory
due to large variations in pancreatic movement
• 4D-CT obtained directly after Contrast enhanced 3D-CT scan
• 4D-CT matched rigidly to 3D-CT bony landmarks for ITV
reconstruction while the final planning treatment is done on 3-D
CT
• Continuous irradiation in free breathing using ITV based on CT
scan in end breathing phase
• Irradiation in specific breathing phases-
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Gating
Real time
tumor
tracking
Active
breathing
coordinato
r

69. 20XX Pitch Deck 73

70. TREATMENT FIELD - AP/PA & LATERAL FIELDS
• Superior field- middle of T11 vertebral body
• Inferior field- at the level L2-L3 to include SM
lymph nodes and third portion of duodenum
• The upper fields extent is sometimes more
when body lesion to obtain adequate margin
• With Lateral fields
o Anterior field margin 1.5-2 cm beyond initial
gross disease
o Posterior margin- 1.5 cm behind the anterior
portion of vertebral body for paraortic nodes
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71. CONVENTIONAL
LOCALIZATION OF TUMOR
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ANTERIOR AND TWO LATERAL
FIELD WITH WEDGES
PRACTICAL RADIOTHERAPY PLANNING – JANE

72. DOSE , FRACTIONATION, DOSE CONSTRAINTS
• Conventional fractionation or moderately hypo-fractionated
• Long course CRT – 1.8 to 3.0 Gy
• Duration of treatment- three to six weeks to total doses of 30-55 Gy , 25-30 # or 10-12 #
• With concurrent chemo- capecitabine, C.I. 5-FU, weekly gemcitabine
• ORGAN AT RISK
 Duodenum
 Stomach
 Small bowel
 Liver
 Kidney
 Spinal cord
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73. 20XX Pitch Deck 77
ORGAN AT RISK

74. DEFINING THE GTV ( ALL
INDICATION EXCEPT
ADJUVANT)
• GTV delineate in pancreatic phase
planning CT
• GTV- primary tumour and
radiologically enlarged lymph nodes
• For SBRT, tumour volume only
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DEFINING THE ITV ( ALL
INDICATION EXCEPT
ADJUVANT)
• Internal target volume is created along
the 4D-CT by contouring the tumor on
multiple phases of respiration
• For SBRT, tumour volume
encompassed in all phases of
respiration
• Abdominal compression reduce the
respiratory motion to <5mm but centre
which perform gating or tracking do
not require an ITV

75. DEFINING THE CTV
• Elective nodal irradiation is not recommended in patients receiving CRT or
SBRT for LAPC
• If ENI is treated based on pattern of nodal involvement
• LAPC- ENI is not recommended because CRT is commonly delivered after a
course of induction chemotherapy and in patients receiving SBRT , additional
expansion of ITV is not usually applied to take CTV into account
• For adjuvant CRT- to create the overall CTV, merge all subvolumes of table 2b
& add this volume to exclude overlaps with normal organs
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76. 20XX Pitch Deck 80

77. 20XX Pitch Deck 81
AORTA (BLUE) CELIAC ARTERY( YELLOW) SMA (GREEN) PORTAL
VEIN(PINK)

78. DEFINING THE PTV
• Is required to compensate for setup errors
 4D available- ITV + 0.5-1cm
 If 4D not available- GTV( or primary CTV) and elective nodal CTV ( if used) +
1.5cm (A-P,L); and 2cm margin in cranio-caudal directions
 For SBRT, all ITV are further expanded to obtain PTV, usually 0-5mm margin
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79. NORMAL DOSE CONSTRAINTS FOR CONVENTIONAL RT
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80. 3D-CRT VS IMRT (1999-2001)
• Analysis of DVH and NTCP of
small bowel showed that IMRT has
the potential to significantly
improve radiotherapy of pancreatic
cancers by reducing normal tissue
dose and simultaneously allowing
escalation of dose to further
enhance locoregional control.
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81. DVH – 3DCRT VS IMRT
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82. 3D-CRT VS IMRT
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IMRT 3D-CRT P-values
% small
bowel>50
Gy
19.2 31.4 0.04
% small
bowel >60
Gy
12.5 19.8 0.03
Dose to 1/3
volume
small
bowel
30 38.5 0.006
% small
bowel
NTCP
9.3 24.4 0.02

83. POSSIBLE ADVANTAGES OF IMRT/VMAT
• Setup uncertainties decreased – reduced PTV margin
• Organ motion accounted for
• Better sparing of OAR in close vicinity to target
 Dose escalation can be planned where necessary
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84. SBRT
• Variable dose schedules
• Common schedule - 30-33 Gy/ 6-8 Gy per fraction/ 3-5 fractions, SIB upto 40 Gy
to tumor vessel interface
• Dose limiting OARs - duodenum and stomach
• Others- liver, kidney, spinal cord and colon
• Prophylactic PPI to reduce duodenal and gastric erosions (may continue for 3-6
months as necessary)
• Motion management is necessary
• Pre-treatment, volumetric IGRT with CBCT before each fraction is mandatory
• Quality assurance should be performed in minimum weekly intervals
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85. NORMAL DOSE CONSTRAINTS FOR 3#/5# SBRT
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86. INTRAOPERATIVE RADIATION THERAPY
• No randomized trials
• Not a standard but may serve as a promising approach for BAPC/LAPC
• Permits high dose RT directly to tumor without the morbidity associated
with irradiation of adjacent normal tissues, particularly small bowel
• Has been explored in conjunction with preop CRT, with possibly higher
local control
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87. Patient Selection
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IOERT Irradiation

88. 20XX Pitch Deck 92

89. IOERT
• Long term survival and disease control are achievable with LAPC
• IOERT as a part of multimodality Rx has proven to promote high local
control without significant increase in treatment toxicity
• IOERT is a risk-adaptable technique in the era of personalised oncology
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90. 20XX Pitch Deck 94
TECHNIQUE WHICH
SETTINGS
DOSES TRIAL CONCURRENT
CHEMOTHERAPY
Conventional RT ADJUVANT SPLIT COURSE
20Gy – 2weeks-20Gy
ESPAC-1 5-FU
Conventional RT ADJUVANT SPLIT COURSE
20Gy – 2weeks-20Gy
GITSG 5-FU
Conventional RT ADJUVANT 50.4 Gy RTOG 9704 5-FU
Conventional RT ADJUVANT SPLIT COURSE
20Gy – 2weeks-20Gy
EORTC 40891 5-FU
Conventional RT ADJUVANT 50.4 Gy EORTC 40013 GEMCITABINE
Hypofractionated RT NEOADJUVAN
T
36Gy PREOPANC-III GEMCITABINE
Hypofractionated RT NEOADJUVAN
T
35-40 Gy MAYO CLINIC 5-FU
CONVENTIONAL RT NEOADJUVAN
T
50.4Gy ESPAC-5 CAPECITABINE
CONVENTIONAL RT NEOADJUVAN 50.4Gy LAP07 TRIAL CAPECITABINE
New updates
• TRK fusion +ve cancers- TRK
inhibitors Larotectinib &
entrectinib are approved
regardless of histology
• Second line therapy for TRK +ve
tumours
New updates
• RAS G12C- Mutation , patients
who progressed on initial
chemotherapy
• Sotorasib – FDA approved in
LAPC and metastatic NSCLC

91. METASTATIC CA PANCREAS
• Palliative systemic chemotherapy can improve the disease related
symptoms and prolong survival
• Patients with metastatic pancreatic cancer should be offered aggressive
treatment for pain and other symptoms related to the cancer.
• Referral for a palliative care consultation should be considered early in the
treatment course, especially for patients with a high symptoms burden.
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92. 20XX Pitch Deck 96
• Two trials have shown a clear survival benefit for combination therapy FOLFIRINOX
and GEMCITABINE + NAB-PACLITAXEL respectively vs gemcitabine alone
• In the COCHRANE META-ANALYSIS, which included eight randomised trials of
chemotherapy vs supportive care alone for advanced pancreatic cancer,
chemotherapy significantly improved one-year mortality
• Patient with ECOG>3 or poorly controlled comorbid conditions should be offered
systemic therapy only on an individualised, case by case , supportive case should
be emphasised

93. SUPPORTIVE CARE IN LOCALLY
ADVANCED/METASTATIC
• Early palliative care involvement- assessment of symptom burden,
psychological status and social supports
• Pain- opioid medication, with adjuvant medication like gabapentin (WHO pain
ladder score), early celiac plexus neurolysis
• Managing biliary & gastric outlet obstruction- placement of metallic stents or
surgical bypass for those in whom stent placement is not possible
• VTE prophylaxis – LMW heparin, low dose ultra fractionated heparin
• Weight loss and anorexia- all patients to meet nutritionist or dietician and use
of appetite stimulants such as megestrol acetate
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94. PHASE III STUDIES FOR METASTATIC CA
PANCREAS
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95. DMMR/ MSI-H
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• Patients with MSI-H tumors respond
to checkpoint inhibitor
immunotherapy
• Although there are no phase-II
studies for first line treatment , we
believe that it is reasonable to
consider first line checkpoint
inhibitor immunotherapy in the rare
group of individuals
HRR DEFICIENCY
• HRR deficiency patients are
sensitive to platinum agents and
PARP inhibitor
• FOLFIRINOX , GEM+CIS, FOLFOX
• Maintenance treatment with PARP
inhibitor will be benefitted
There was no statistically
significant difference. PFS2
showed a clear trend for treatment
benefit beyond disease
progression in favor of olaparib
Median PFS (7.4 vs 3.8
months) p- 0.06 with
maintenance olaparib
Twice as many patients
were progression free
(22 vs 9.6%) & OS in
similar in both groups

96. PATIENTS WITH HRR DEFICIENCY / STATUS
PENDING
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97. POLO TRIAL- PARP INHIBITOR
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Median PFS (7.4 vs
3.8 months) p- 0.06
with maintenance
olaparib
Twice as many
patients were
progression free (22
vs 9.6%) & OS in
similar in both
groups
There was no statistically
significant difference. PFS2
showed a clear trend for treatment
benefit beyond disease
progression in favor of olaparib

98. MPACT STUDY- NAB-
PACLITAXEL+GEM VS GEM
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Median OS (9.8 vs 7.5
months) &
PFS ( 5.5 vs 3.7 months)
p <0.01
ACCORD 11- PHASE III TRIAL
Median PFS (6.4 vs 3.3 months) &
overall survival (11.1 vs 6.8 months)-
superiority of FOLFIRINOX over
GEMCITABINE

99. OTHER COMBINATIONS OF GEMCITABINE
• GEMCITABINE PLUS FU
• GEMCITABINE PLUS CAPECITABINE
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FLUOROPYRIMIDINES
• Fluorouracil
• Capecitabine
• S-1 derivative
 tegafur, gimeracil and oteracil
 It is approved in JAPAN for adjuvant therapy of gastric cancer and in Europe too
 In phase III GEST trial, s-1 (80-120mg) daily on days 1 to days 28 with cycles repeated
every 42 days was directly compared with gemcitabine monotherapy (100mg/m2) on
d1,8,&15 or s-1 plus gemcitabine

100. POST TREATMENT
SURVEILLANCE
METASTATIC DISEASE
• RADIOGRAPHIC ASSESSMENT- first
response assessment using cross
sectional imaging should be offered at two
to three months after initiation of therapy
• TUMOR MARKER RESPONSE- serum CA
19-9 levels are not considered an optimal
substitute for imaging for assessing
treatment response.
• Suspected disease progression based on
rising CA19-9 levels should be confirmed
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POST TREATMENT
SURVEILLANCE
NON-METASTATIC DISEASE
• A follow up visit every 3-4 months that
includes a physical examination, LFT &
RFT for 2 yrs, after which time intervals
can be increased to every 6 months
• Testing for serum tumor markers , if
initially elevated and cross sectional
imaging at least every 3-4 months
during first two years, then every six
months once disease stability is
established
• Routine use of PET-CT imaging is not
recommended

101. CONCLUSIONS
• h
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102. • h
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103. • h
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104. • h
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