1. CARCINOMA
PANCREAS

2. Anatomy
 The pancreas is an elongated, coarsely lobulated
gland lying transversely and retroperitoneally in the
posterior abdomen
 at approximately the L1 to L2 level

4. Arterial Supply

5. Venous Drainage

6. Lymphatic Drainage

7. Innervation

8. Epidemiology
 Pancreatic cancer is the fifth leading cause of cancer
mortality among men and women of all ages
 a male-to-female ratio of 1.3 : 1.
 Diagnosis is rare before age 45 but rises sharply
thereafter

9. Causal Factors
 Smoking -raises the relative risk 1.5 times.
 Alcohol
 Diets high in meat or fat also have been linked to
increased risk
 a diet of fresh fruits and vegetables has been found to be
protective.
 An increased incidence also is found with a prior history
of surgery for peptic ulcer disease

10.  chronic pancreatitisare associated with
pancreatic cancer
 One study showing 7 times higher risk
 Long-term diabetes appears to be a risk
factor for pancreatic cancer
 Chemical agents
 Workers employed in manufacturing 2-
naphthylamine, benzidine,and gasoline are
reported to have a fivefold increased risk

12. Genetics, and Cytogenetic Abnormalities
 Pancreatic cancer is thought to have a familial
component in approximately 10% of cases
 There are four specific genes identified as crucial in
the development of pancreatic cancer:
 p16, p53, DPC4, and BRCA2
 An example is the k-ras oncogene, which is often
activated in human pancreatic duct carcinomas.

13.  95% of pancreatic adenocarcinomas contain k-ras
oncogenes activated by a mutation at codon 12.

16.  Germline mutations in the STK11 gene result in
Peutz-Jeghers syndrome
 individuals have gastrointestinal polyps and a highly
elevated risk for colorectal cancers
 highly elevated risk for developing pancreatic cancer,
reported to be increased by as much as 132-fold

17.  Familial Malignant Melanoma syndrome (also
known as Melanoma-Pancreatic Cancer syndrome or
Familial Atypical Multiple Mole Melanoma
syndrome [FAMMM])
 caused by germline mutation of the CDKN2A
(p16INK4a/p14ARF) gene.
 This syndrome is associated with a 20-fold to 47-
fold increased risk for pancreatic cancer

18.  Lynch syndrome also have an estimated 9- to 11-fold
elevated risk for pancreatic cancer
 BRCA 1 N 2
 The risk of pancreatic cancer is elevated 2- to 6-fold
in these patients
 age of onset is younger than average

19.  As many as 80% of patients with a family history of
pancreatic cancer have no known genetic cause.
 having just 1 first-degree relative with pancreatic
cancer raises the risk of pancreatic cancer by 4.6 fold
 having 2 affected first-degree relatives raises risk by
about 6.4-fold

20. Pancreatic Cancer Screening
 high-risk individuals
 defined as first-degree relatives of patients with
pancreatic cancer from familial kindreds;
 carriers of p16 or BRCA2 mutations with an affected
first-degree relative
 patients with Peutz-Jeghers syndrome
 patients with Lynch syndrome and an affected first-
degree relative with pancreatic cancer.

21. Pathologic Conditions
 The most common type of pancreatic cancer is of
ductal origin, comprising from 75% to 90% of
patients
 It is twice as common in the head as in the body or
tail
 Less frequently occurring exocrine tumors, such as
cystadenocarcinoma or intraductal carcinoma, are
more common in women

22.  Solid and cystic papillary neoplasms, also
known as Hamoudi tumors, occur in women
in their third decade of life
 rarely metastasize, and have a good
prognosis
 Rare acinar cell cancers are associated with
fat necrosis and high lipase production and
have a poor prognosis
 may be associated with a clinical picture that
includes rash, eosinophilia, and
polyarthralgia

23.  Giant cell tumors, which account for only a
small percentage of pancreatic cancers, are
very large and aggressive and have a very
poor survival rate
 metastases in the pancreas with the most
frequent primary sites being breast, lung, or
melanoma
 5% of pancreatic cancers are of endocrine
origin

24.  Location
 66% in Head and Uncinate Process
 Dx earlier ,
 Symptomatic
 15% in Body
 10% in Tail
 Usually larger & more progress at time of Dx
 Asymptomaic
 Other diffuse involvement

25. Clinical Presentation
 More than 80% of patients present with pain,
jaundice, or both and weight loss
 Infrequently, patients may present with migratory
thrombophlebitis (Trousseau sign)
 or with a palpable gallbladder (Courvoisier sign).

28. Evaluation

29.  The most commonly used diagnostic and staging
examination is an abdominal CT scan
 Over 90% of patients deemed unresectable by CT are
actually unresectable at operation
 CT can be utilized to facilitate fine-needle aspiration.

31. EUS
 In this procedure, an endoscope with an ultrasound
transducer at its tip is passed into the stomach and
duodenum
 it provides high-resolution images of the pancreas and
surrounding vessels and facilitates needle biopsies
 EUS is usually performed in conjunction with endoscopic
retrograde cholangiopancreatography (ERCP)
 This combined diagnostic approach allows for staging,
therapeutic stenting of the common bile duct when
indicated, and retrieval of tumor cells by fine-needle
aspiration

32.  (MRI) including high-resolution imaging, fast
imaging, volume acquisitions, functional imaging,
and MR cholangiopancreatograph
 have led to an improved ability of MRI to diagnose
and stage pancreatic cancer
 Used in patients with poor renal function
 Small foci of hepatic mets are better detected by MRI

33. PET
 Initial studies showed (PET) has a higher sensitivity,
specificity, and accuracy than CT in diagnosing
pancreatic carcinomas
 more accurate than CT in identifying malignant
pancreatic cystic lesions

34. STAGING LAPROSCOPY
 current imaging techniques cannot visualize small (1
to 2 mm) liver and peritoneal implants
 staging laparoscopy has been used preoperatively to
exclude intraperitoneal metastases
 can detect intraperitoneal metastases in up to 37% of
patients with apparently locally advanced disease by
CT

35.  WHEN?
 borderline resectable disease
 markedly elevated CA 19-9
 large primary tumors
 large regional lymph nodes
 highly symptomatic

36. Biopsy
 Although a pathologic diagnosis is not required
before surgery
 it is necessary before administration of neoadjuvant
therapy and for patients staged with locally
advanced, unresectable pancreatic cancer or
metastatic disease
 often made using fine-needle aspiration (FNA)
biopsy with either EUS guidance (preferred) or CT

37.  Pancreatic ductal brushings or biopsies can also be
obtained at the time of ERCP

38. STAGING

40. Diagnosis & staging
• Stage at Diagnosis
– 7% : Localized stage
• 5yr-SR = 20.3%
– 26% : +ve Regional LN involvment / T3 up
• 5yr-SR = 8.0%
– 52% : metastasis (Distant stage)
• 5yr-SR = 1.7%
– 15% : unknown stage information
• 5yr-SR = 4.1%
• Overall 5yr-SR = 5%

41. MANAGEMENT
 RESECTABLE
 BORDERLINE RESECTABLE
 UNRESECTABLE BUT NOT METASTATIC
 METASTATIC

42. CRITERIA DEFINING RESECTABILITY
STATUS
 Resctable tumors
 No distant metastases
 No radiographic evidence of superior mesenteric
vein (SMV) or portal vein (PV) distortion.
 Clear fat planes around the celiac axis, hepatic
artery, and SMA

43. borderline resectable
 No distant metastases
 Venous involvement of the SMV or PV with distortion or
narrowing of the vein or occlusion of the vein with
suitable vessel proximal and distal, allowing for safe
resection and replacement.
 Gastroduodenal artery encasement up to the hepatic
artery with either short segment encasement or direct
abutment of the hepatic artery without extension to the
celiac axis.
 Tumor abutment of the SMA not to exceed greater than
180 degrees of the circumference of the vessel wall

44. UNRESCTABLE

45. Management of Resectable and
Borderline Resectable
Disease

46.  Surgical resection is the only potentially curative
technique for managing pancreatic cancer
 more than 80% of patients present with disease that
cannot be cured with surgical resection

47.  The goals of surgical extirpation of pancreatic
carcinoma focus on the achievement of an R0
resection
 a margin positive specimen is associated with poor
long-term survival
 Achievement of a margin negative dissection must
focus on meticulous perivascular dissection of the
lesion in resectional procedures, recognition of the
need for vascular resection and/or reconstruction

48.  prognostic indicators for long-term patient survival
 Negative margin status (ie, R0 resection)
 Tumor DNA content
 tumor size
 absence of lymph node metastases

49.  When deciding whether a patient is a surgical
candidate.
 Age of the patient
 Comorbidities
 performance status
 frailty are all things to be discussed

50. Primary Surgery for Pancreatic Cancer
 The nature and extent of the surgery for resectable
tumors depend on the location and size of the tumor.
 Because tumors of the body and tail cause symptoms
late in their development
 they are usually advanced at diagnosis and are rarely
resectable.

51. Surgical Procedures
 Tumors of the Body
and Tail
 Distal Pancreatectomy
 Removal of body & tail of
pancreas
 spleen

52. Surgical Procedures
 Head of the
pancreas: Whipple
Procedure
 Removal of:
 Distal stomach
 Duodenum and
proximal jejunem
 Head of pancreas
 Gallbladder and
common bile duct

54. Complications
 Whipple Procedure
 bleeding
 Gastroparesis
 Pancreatic duct leak
 Bile duct leak
 Diabetes
 malabsorption
 Distal pancreatectomy
 Bleeding
 Pancreatic duct leak
 Malabsorption
 diabetes

55.  Total pancreatectomy
 If the cancer diffusely involves the pancreas
 or is present at multiple sites within the pancreas
 where the surgeon removes
 Entire pancreas, part of the small intestine, a portion
of the stomach, the common bile duct, the
gallbladder, the spleen, and nearby lymph nodes

56.  If the tumor is found to be unresectable during
surgery
 biopsy confirmation of adenocarcinoma can be done.
 If a patient with jaundice is found to be unresectable
at surgery stenting or biliary bypass can be done

57. Lymph node dissection
 A standard lymphadenectomy in patients undergoing
pancreatoduodenectomy
 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 pancreatoduodenal lymph
nodes

58. Preoperative Biliary Drainage
 The main goals of preoperative biliary drainage are
to alleviate the symptoms of pruritus and cholangitis
 and to potentially make surgery less morbid by
improving liver function preoperatively.
 But earlier study does not support use of
preoperative drainage routinely

59.  It is considered
 When surgery is delayed due to sepsis
 When planned for neoadjuvant therapy

60. ADJUVANT THERAPY
 Even with R0 resections, recurrence rates are very
high in this disease.
 Additional therapy is required for all patients with
resected pancreatic adenocarcinoma.

61. PATTERN OF FAILURE
 the bed of the resected pancreas (local recurrence)
 the peritoneal cavity
 liver

62.  High local failure rates of 50% to 86% occur despite
resection
 because of frequent cancer invasion into the
retroperitoneal soft tissues
 high rates of lymphatic involvement
 the inability to achieve wide retroperitoneal soft-
tissue margins because of anatomic constraints to
wide posterior excision

63. EARLIER STUDIES
 GITSG trial, which enrolled patients with completely
resected pancreatic cancer
 A total of 46 patients were randomized to undergo
observation
 or to receive bolus 5-FU (500 mg/m2 daily) during
the first 3 days of each period of split course
radiation
 20 Gy in 10 fractions, 2 weeks break, and
resumption of radiation to a total dose of 40 Gy

64.  followed by up to 2 years of weekly bolus 5-FU
 striking survival advantage for patients receiving
combined modality therapy compared with survival
of patients who underwent surgery alone
 median 21.0 months vs. 10.9 months, respectively; P
= .03

65.  The findings from the GITSG study could not be
reproduced by a subsequent trial conducted by the
EORTC
 EORTC-40891 randomized 218 patients
 undergo observation or to receive infusional 5-FU
(25 mg/kg/d to a maximum dose of 1,500 mg/d)
given concurrently during the first week of two split
courses of radiation (total dose 40 Gy)
 Result showed trend towards improvement in OS but
not statistically significant

66. ESPAC 1 TRIAL

68. RESULTS
 Patients who received chemoradiation did worse
 median survival of 15.9 months
 than those not receiving chemoradiation (median
survival of 17.9 months)
 who received chemotherapy had a median survival of
20.6 months

69.  The investigators concluded that chemoradiation not
only failed to benefit patients but also reduced
survival when given before chemotherapy.

70. FLAWS IN ESPAC 1
 Physicians were allowed to choose which of the three
parallel trials to enroll patients on, creating potential
bias
 Patients could receive background•chemoradiation
or chemotherapy as decided by their physician.
 Approximately one third of the patients enrolled on
the chemotherapy versus no chemotherapy trial
received background chemoradiation therapy or
chemotherapy

71.  The radiation was given in a split-dose fashion, with
the treating physician judging the final treatment
dose (40 Gy vs. 60 Gy).
 In the chemoradiation versus no chemoradiation
trial, no maintenance adjuvant chemotherapy was
given
 All these trials do not address local control,
palliation of local symptoms, and quality of life

72. Studies of Gemcitabine-Based Adjuvant Therapy

75.  With available studies role of RT in adjuvant setting
is not well established
 Adjuvant chemotherapy has definite role in adjuvant
setting
 It has been suggested patients with R1 resections or
positive lymph nodes may be more likely to benefit
from adjuvant chemoradiation.

76.  To definitively clarify the role of chemoradiation
following gemcitabine monotherapy in the adjuvant
setting
 RTOG is conducting trial 0848.
 Patients without evidence of progressive disease
after 5 cycles of gemcitabine-based chemotherapy
are being randomized to 1 additional round of
chemotherapy
 or 1 additional round of chemotherapy followed by
chemoradiation with capecitabine or 5-FU.

77. Neoadjuvant Therapy
 Approximately 25% of patients do not receive
adjuvant therapy in a timely manner after surgery or
do not receive it at all
 Given the high recurrence rates after surgical
resection, pancreatic cancer is likely a systemic
disease at the time of diagnosis in 80% to 85% of
patients who appear to have resectable disease

78.  with neoadjuvant therapy, 20% to 40% of patients
will be spared the morbidity of resection
 because their metastatic disease becomes clinically
apparent
 Preoperative therapy could theoretically be less toxic
and more effective
 Patients with local and unresectable lesions may be
able to be downstaged to allow for surgical resection

79.  Potential disadvantages include the fact that
 in the absence of staging laparoscopy, some patients with
distant metastatic disease who are unlikely to benefit
from RT will receive unnecessary treatment
 it is possible that local progression during neoadjuvant
therapy will preclude surgical resection
 radiation-related toxicity may impair the patient’s ability
to tolerate surgery
 increase risk of wound complications.

80.  analysis of preoperative vs. postoperative
chemoradiotherapy at M. D. Anderson Cancer
Center
 did not note differences in toxicity or survival.
 Evans et al reported results of a phase II study of 86
pancreas cancer patients with potentially resectable
disease treated with
 preoperative chemoradiotherapy (7 weekly doses of
gemcitabine 400 mg/m2 plus 30 Gy radiation in 10
fractions)

81.  The authors concluded that preoperative
gemcitabine-based chemoradiotherapy identified a
subgroup of patients unlikely to benefit from surgical
resection
 Randomized trials are lacking, but existing data
support further exploration of neoadjuvant
chemoradiotherapy

82. UNRESECTABLE TUMORS
 intermediate prognosis between resectable and
metastatic patients.
 therapeutic options include
 EBRT with 5-FU chemotherapy
 IORT
 EBRT with novel chemotherapeutic and targeted agents.

83. TRIALS
 The Mayo Clinic undertook an early randomized trial
in the 1960s
 64 patients with locally unresectable, nonmetastatic
pancreatic adenocarcinoma received 35 to 40 Gy of
EBRT with concurrent 5-FU versus the same EBRT
schedule plus placebo.
 A significant survival advantage was seen for
patients receiving EBRT with 5-FU versus EBRT only
(10.4 months vs. 6.3 months)

84. RCT IN UNRESECTABLE TUMORS

85.  with the exception of one study
 conventional EBRT combined with 5-FU
chemotherapy has been shown to offer a modest
survival benefit for patients with locally advanced
unresectable pancreatic cancer compared to
radiation alone or chemotherapy alone

86. Intraoperative Radiation Therapy
 Because of the poor local control and results achieved
with conventional EBRT and chemotherapy
 increase the radiation dose to the tumor volume have
been used to improve local tumor control without
significantly increasing normal tissue morbidity
 A lower incidence of local failure in most series and
improved median survival in some have been reported
with these techniques when compared with conventional
external beam irradiation
 but it is uncertain whether this is due to superior
treatment or case selection

87. Chemoradiation Following
Chemotherapy in Locally Advanced
Disease
 Starting with 2 to 6 cycles of systemic chemotherapy
followed by chemoradiation therapy is an option for
selected patients with unresectable disease and good
performance status who have not developed
metastatic disease.

88.  it is highly unlikely that the patient will become
resectable (ie, complete encasement of superior
mesenteric/celiac arteries)
 there are suspicious metastases
 the patient may not be able to tolerate
chemoradiation

89.  Employing an initial course of chemotherapy may
improve systemic disease control in these cases.
 In addition, the natural history of the disease can
become apparent during the initial chemotherapy,
 thus allowing the selection of patients most likely to
benefit from subsequent chemoradiation

90. CHEMOTHERAPY
 Gemcitabine Monotherapy
 In the large phase III CONKO-001 trial, in which 368
patients without prior chemotherapy or RT were
randomly assigned to adjuvant gemcitabine versus
observation
 DFS 13.4 VS 6.9 months
 An absolute survival difference of 10.3% was observed
between the two groups at 5 years (20.7% vs. 10.4%).

91. Gemcitabine Combinations
 Gemcitabine has been investigated in combination
with potentially synergistic agents (such as cisplatin,
oxaliplatin, capecitabine, 5-FU, and irinotecan)
 Two recent meta-analyses of randomized controlled
trials both found that gemcitabine combinations give
a marginal benefit in OS over gemcitabine
monotherapy in the advanced setting, with a
significant increase in toxicity

92. Combination with ERLOTINIB
 phase III, double-blind, placebo-controlled NCIC
CTG PA.3 trial of 569 patients with advanced or
metastatic pancreatic cancer
 randomly assigned to receive erlotinib plus
gemcitabine versus gemcitabine alone
 patients in the erlotinib arm showed statistically
significant improvements?? in OS
 MS 6.24 VS 5.91 months

93. Gemcitabine Plus Cisplatin
 3 phase III trials evaluating the combination of
gemcitabine with cisplatin versus gemcitabine alone
 in patients with advanced pancreatic cancer failed to
show a significant survival benefit for the
combination over the single agent

96.  Gemcitabine dosage
 1000 mg/m² intravenously over 30 minutes.
 repeat at weekly intervals for up to 7 weeks, followed
by one week of rest.
 If toxicity occurs, a dose should be held.
 Subsequent cycles should consist of weekly cycles
for 3 consecutive weeks, out of every 4 weeks
 Erlotinib -100-150 mg/day

97.  FOLFIRINOX
 (oxaliplatin, 85 mg per m2irinotecan, 180 mg per
m2; leucovorin, 400 mg per m2; and fluorouracil,
400 mg per square meter given as a bolus
 followed by 2400 mg per square meter given as a 46-
hour continuous infusion, every 2 weeks

98. RT TECHNIQUES
 Immobilisation
 The patient lies supine in a vacuum moulded bag with
arms above the head in arm rests
 CT scans are acquired as described above with a slice
thickness of 5 mm 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.

99.  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 anterior-
posterior (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

100. Target volume definition
 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.

101.  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.
 It is not necessary to include the whole duodenal
loop in the treatment field

102. Target volume definition
 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

103. CONVENTIONAL FIELD BOARDERS
 Superior and Inferior Borders
 For pancreatic head lesions, to ensure adequate
coverage on the celiac nodes, the superior border
should be at the T10/T11 level
 the lower border at the L3/L4 level, depending on
the preoperative staging studies

104.  Lateral field boarder should include tumor with 2.5-
3 cm margin
 Posteriorly should include 1.5-2 cm of vertebral body
 Anteriorly to cover tumor with 1.5-2 cm margin

106.  OAR include the spinal cord, kidneys, liver and small
bowel.

109. RTOG GUIDELINES IN POST OP
 Treatment Volumes: GTV
 By definition there is no GTV (tumor has been resected)
 Location of pancreatic tumor prior to resection must be
reviewed and contoured based on preoperative axial
imaging/simulation
 Pre-operative diagnostic or simulation scans can be fused with
post-operative CT to facilitate localization of tumor bed
 Surgical and pathological information must be reviewed at
time of treatment planning

110. CTV
 The post operative CTV is that area where there is
likely tobe the highest concentration of residual sub-
clinical tumor
 that can be treated with radiotherapy without
resulting in a treatment volume that encompasses an
excessive amount of normal organs and normal
tissue.

111. CTV

112. ROI Delineation:
 CA and SMA
 The most proximal 1.0-1.5 cm of the celiac artery
(CA)
 The most proximal 2.5 to 3.0 cm of the superior
mesenteric artery (SMA

113. PV
 Include the portal vein (PV) segment that runs slightly to
the right of, in front of (anterior) and anteromedial to the
inferior vena cava (IVC).
 Contour from the bifurcation of the PV to, but do not
include, the PV confluence with either the SMV or
Splenic Vein (SV).
 – The PV bifurcation can be extrahepatic or almost
intrahepatic.
 – The PV most often will merge first with the SMV, but
may merge with the SV.

114. Post-op Bed

115.  The pancreaticojejunostomy (PJ) is identified by
following the pancreatic remnant medially and
anteriorly until the junction with the jejunal loop is
noted.
 The aorta (Ao) from the most cephalad contour of
either the celiac axis, PV, or PJ (whichever among
these 3 is the most cephalad) to the bottom of the L2
vertebral body.
 If the GTV contour extends to or below the bottom of
L2 then contour the aorta towards the bottom of the
L3 vertebral body as needed to cover the region of
the preoperative tumor location

116. ROI Expansions
 The celiac axis, SMA, and PV ROI’s should be
expanded by 1.0 - 1.5 cm in all directions..
 The PJ should be expanded 0.5 -1.0 cm in all
directions.
 Delineated clips may be expanded by 0.5 – 1.0 cm in
all directions or used without expansion

117.  Suggested approximate expansion amounts for the
aortic ROI are as follows:
 2.5 to 3.0 cm to the right
 1.0 cm to the left
 2.0 to 2.5 cm anteriorly
 0.2 cm posteriorly towards the anterior edge of the
vertebral body
 Goal is to cover paravertebral nodes laterally while
avoiding kidneys

118.  The CTV should then be created by merging the
above ROI/ ROI expansions
 CA, SMA, PV, GTV, Aortic, PJ, HJ, clips

121. CTV EXPANSION

122. NORMAL STRUCTURES

124.  Dose-fractionation
 Radical (in combination with chemotherapy with
gemcitabine or 5FU)
 45–50.4 Gy in 25–28 fractions of 1.8 Gy given in 5–
51⁄2 weeks.

125. Role of IMRT
 Ben-Josef and colleagues described using an IMRT
approach to treat locally advanced and resected
pancreatic cancer with concurrent capecitabine
 Using this technique, the primary tumor (or tumor bed if
treating postoperatively) was treated with 54 Gy and the
lymph nodes with 45 Gy
 Acceptable toxicity occurred if the following dose
limitations were observed:
 50% of each kidney below 20 Gy, 67% of liver below
35 Gy, 90% of small bowel below 45 Gy, 90% of stomach
below 45 Gy, and 90% of spinal cord below 45 Gy