Nghiên cứu đặc điểm hình ảnh, vai trò của FDG PET CT trong đánh giá giai đoạn, phát hiện tái phát ở bệnh nhân ung thư vú trước và sau điều trị tt tiếng anh

MINISTRY OF EDUCATION
AND TRAINING

MINISTRY OF
NATIONAL DEFENCE

VIETNAM MILITARY MEDICAL UNIVERSITY

NGUYEN TRONG SON

STUDY ON 18FDG UPTAKE CHARACTERISTICS,
THE ROLE OF PET/CT IN DIAGNOSIS OF STAGE,
RECURRENCE, METASTASES IN BREAST
CANCER PATIENTS BEFORE AND POST
TREATMENT
Specialty : Radiology and Nuclear Medicine
Code
: 9720111

PH.D. THESIS SUMMARY

HANOI - 2019


THE RESEARCH WAS FINISHED AT
VIETNAM MILITARY MEDICAL UNIVERSITY

Supervisors:
1. Prof. Ph.D. Mai Trong Khoa
2. Assoc.Prof. Ph.D. Nguyen Danh Thanh

Judge 1: Prof. Ph.D. Nguyên Ba Đuc
Judge 2: Assoc.Prof. Ph.D. Le Ngoc Ha
Judge 3: Assoc.Prof. Ph.D. Bui Van Lenh

The thesis will be defended before the Thesis Assessment Council at
Institute level
At: Vietnam Military Medical University
Date

month

year

The thesis can be found at:
- National Library
- Vietnam Military Medical University Library


LIST OF WORKS RELATED TO THE THESIS
HAS BEEN PUBLISHED
1.

Nguyen Trong Son, Nguyen Danh Thanh (2019). The role of
18

FDG PET/CT in the diagnosis of recurrence and distance

metastases in 98 post treatment breast cancer patients, J.of
Practical Medicine, 7 (1102): 27-30.
2.

Nguyen Trong Sơn, Nguyen Danh Thanh (2019). Results of
18

FDG PET/CT stage diagnosis in 55 breast cancer patients. J.

of Community Medicine, 4 (51): 48-52.


1
INTRODUCTION
Breast cancer (BC) is the most common female cancer, with
higher rate of morbidity in Europe and American, lower in Asia and
Africa. In Viet Nam, BC is the most common female cancer with
morbidity rate is increasing each year.
The diagnosis of BC is based on clinical history, histology and
diagnosis imaging such as mammography, ultrasound, CT scan,
MRI... SPECT (Single Photon Emission Computed Tomography) and
PET (Positron Emission Tomography) are nuclear imaging method,
which have high value in clinical practice and BC.
PET/CT with 18FDG can detect early changes of metabolic shift of
disease, even before physiological and anatomical changes. In
patients with BC, 18FDG PET/CT allows us to find axillary node,
extraaxillary locoregional node (supraclavicular or internal mammary
nodes), thoracic and abdominal metastases, bone metastases, evaluate
cancer stage before treatment. After 18FDG PET/CT, changed the
stage diagnosis in 1/3 of patients and treatment tactics was changed
in 1/6 of patients with BC.
18
FDG PET/CT also has high accuracy rate, sensitivity (Se) and

specificity (Sp) in follow up scan to find recurrence, metastases after
treatment. Especially when patient with clinical symptoms of
recurrence or high serum concentration of tumor markers but has no
abnormal sign in other conventional imaging method, or even when
patients has no clinical symptoms.
In Vietnam nowadays, it had a few studies about value of 18FDG
PET/CT in patients with BC. But there didn't have a systematic study
about characteristics of 18FDG uptake in tumors, recurrence and
distance metastases lesions; axilary nodes, extraaxilary nodes; stage
diagnosis value of 18FDG PET/CT, at which clinical stage 18FDG
PET/CT should be intiated? And which the role of PET/CT for follow
up?


2
So we did our study about "Study on 18FDG uptake
characteristics, the role of PET/CT in diagnosis of stage, recurrence,
metastases in breast cancer patients before and post treatment" with
following research objectives:
1/ Study on 18FDG uptake characteristics, the role of PET/CT in
diagnosis of stage in breast cancer patients pre-treatment.
2/ Evaluate the role of 18FDG PET/CT in finding recurrence
lesions and metastases in breast cancer patients post-treatment.
- New contributions
The results of thesis confirmed the value of the 18FDG PET/CT
method in the staging diagnosis of breast cancer patients: tumor
detection at the rate of 100% of the patients, detected nodal
metastases on 36/55 patients (65.6%) and metastases on 9/55 patients
(16.4%). 18FDG PET/CT method changed the diagnosis, were
upstaging TNM of 21/55 patients (38.2%), which is the basis for

physicians to select the appropriate treatment method. Treatment
tactics was changed in 9/55 patients (16.4%).
The thesis demonstrated the role of 18FDG PET/CT in lymph node
detection, distance metastases, local recurrence of tumor in post
treatment breast cancer patients.
The thesis has identified the 18FDG uptake characteristics of
tumors, nodes, and distance metastases of breast cancer patients, the
relations between SUVmax of primary tumor with lymph node status,
distance metastases, tumor size and histological grade,
histopathological type. It also found the relations between SUV max of
metastatic nodules with location and lymph node size.
- The dissertation structure:
The dissertation consists of 118 pages, including: Introduction (2
pages), Overview (40 pages), Subjects and method (10 pages),
Results (29 pages), Discussions (34 pages), Conclusions (2 pages)
and Proposals: 1 page. It also have 35 tables, 7 charts, 3 pictures, 138
references (21 Vietnamese and 117 English), and Index.


3
CHAPTER 1: OVERVIEW
Using

18

FDG PET/CT to find tumor, lymph nodes and distance

metastases has important role in stage diagnosis of cancer and follow
up post-treatments.

18

FDG PET/CT help us early and accurately

evaluate treatments responses, and easily distinguish between tumor
and scar, fibrosis... and early detect recurrence lesions, better than
conventional imaging methods (CT scan, MRI...), give us more
accurate in biopsy, reduce false negative rate.
Conventional imaging methods such as CT, MRI often has
difficulty and easily give false negative when metastases and lymph
nodes are size smaller than 1cm. 18FDG PET/CT have higher value of
Se and Sp in cancer staging pre and post-treatments compare to
conventional CT scan. 18FDG PET/CT also has about 10-15% more
accurate compare to PET scan alone in cancer staging diagnosis.
Se and Sp value of 18FDG PET/CT in BC diagnosis is 80-96% and
83-100% respectively.

18

FDG PET/CT Sp value in distinguishing

between benign and malign lesions is about 90%.
Using 18FDG PET/CT can detect lymph nodes, which sizes are not
big enough to be found in conventional CT scan.

18

FDG uptake in

PET/CT allows us to detect axillary nodes and lymph nodes group III

as supraclavicular node, inner mammary node...
18

FDG PET/CT is prefer to evaluated local and distance

metastases in advanced stage of BC. It was helpful for detecting
occult non-symptoms metastases lesions, which can be missed in
conventional imaging methods.
18

FDG PET/CT has important role in determining the stage of

disease for patients in stage IIB (T2N1, T3N0) and IIIA (T3N1).


4
Beside the role of staging diagnosis, the

18

FDG uptake by a

primary tumor also has high value in prognosis. Patient who has
higher SUVmax in primary tumor has poorer outcome. Patient who has
ER (+)/ Her2 (-) and high SUVmax has shorter over survival time.
Post-treatments, local recurrence often found in 5-9% patient in
N0 stage, increase to 20-28% in patient with axillary nodes.
Mammography is currently preferred methods for detecting local
recurrence and post-treatment follow up. MRI is also used to
distinguish between scars and recurrence lesions, or to diagnose

complications. 18FDG PET/CT has high value in detecting abnormal
after radiotherapy treatment or mammoplasty complications.
Locations with high rate of recurrent post-treatments are thoracic
wall and upper clavical nodes. 18FDG PET/CT is useful for detecting
local recurrence and distance metastases post-treatments.
CHAPTER 2: SUBJECTS AND METHODS
2.1 SUBJECTS
Patients

with

a

cancer

diagnosis

were

confirmed

by

histopathology as breast carcinoma, with full records.
- Group 1: 55 patients with BC, underwent 18FDG PET/CT before
treatment to diagnosis cancer stage, study on uptake characteristic
18

FDG of turmors, lymph nodes, metastases.
- Group 2: 98 post- treatments (surgery +/- radiotherapy +/-

chemotherapy) breast cancer patient, underwent 18FDG PET/CT to:
+ Subgroup 1: post-treatments follow up: time from last treatment
to PET/CT time was at least 3 months.
+ Subgroup 2: patients had clinical symptoms, with recurrence
lesions and metastases detected on other conventional imaging
methods as mammography, CT. MRI, ultrasound, bone scintigraphy.


5
+ Subgroup 3: patients with high tumor markers concentrations
(CEA, CA15.3).
- Exclude patients who are pregnant or breastfeeding; Patients at
risk of near death due to other serious illnesses.
PET/CT was taken at Viet Duc Hospital, Bachmai Hospital and K
hospital from 2013 to march 2019.
2.2. METHODS
2.2.1. Study design
Non-control prospective clinical study, cross-sectional description
with convenience sampling.
2.2.2. Steps to proceed
2.2.2.1. Clinical and subclinical
In group 1: Pre-treatment breast cancer patients
- Clinical: age; reason why they came to hospital; form of breast
cancer detection; some subclinical characteristics.
- Some pathological characteristics of tumor:
+ Tumor locations; lymph node status, metastases.
+ Histopathology.
+ Histological stage: I, II, III.
+ Pathological type: invasive ductal carcinoma, invasive lobular

carcinoma.
+ Clinical subtype: Luminal A, Luminal B, Her2-positive, triple
negative.
+ Tumor markers test: CEA (normal:<4.3ng/ml), CA15.3 (normal:
<25 U/ml).
- TNM staging before

18

FDG PET/CT according to American

Joint Committee on Cancer (AJCC - 2017).


6
In group 2: breast cancer patients after treatment
- Age; tumor size; primary tumor location (left, right or both).
- Treatments were used: surgry, radiotherapy, chemotherapy.
- Time from disease, from the end of treatment until taken 18FDG
PET/CT.
- Tumor markers test: CEA, CA15.3.
2.2.2.2. 18FDG PET/CT procedure
18

FDG PET/CT was processed according to American College of

Radiology (ACR) and European Association of Nuclear Medicine
(EANM) guidelines.
- Radiopharmaceutical and PET/CT systems:
+ Radiopharmaceutical: solution-based 18FDG (2-flouro-2-deoxyD-glucose) was produced in Cyclotron center of Vietnam Military

Central Hospital 108 and Institute of Nuclear Science and
Technology.
Used dosage: 0.15mCi/kg (5.55MBq/kg); injected through venous
system 45 minutes before scan process.
+ PET/CT system: GE PET/CT Discovery ST4 system, Siemens
PET/CT Biograph 6 True Point system and GE PET/CT Discovery
IQ system.
- Analyze imaging results:
+ Abnormal image included: abnormal anatomical structures,
locations and organs. Increase 18FDG uptake in primary tumor, lymph
nodes, and distance metastases lesions.
+ All images were recorded in CDRom, and were analyzed by
two nuclear medicine doctors, using TRUE D software system.


7
+ The

18

FDG PET/CT image is firstly analyzed qualitatively:

location, affected organ. Next step determines the size, SUV max of
tumors, lymph nodes, distance metastase lesions...
+ Evaluation of lymph node metastases: number of lymph nodes,
supraclavicular lymph nodes, inner mammary lymph nodes... newly
detected on 18FDG PET/CT.
+ Metastases and recurrence lesions: number, location of lesions,
18

FDG uptake SUVmax.
- Measurements on 18FDG PET/CT images:
In patients group 1: before treatment
+ Tumors location; size (cm); tumor 18FDG uptake SUVmax
+ Lymph nodes: Number; size; SUVmax
+ Metastases lesions: number; size; SUVmax
+ Some factors related to SUVmax of primary tumors and lymph

nodes.
In patients group 2: breast cancerpatients after treatment
+ Lymph nodes: Number, location, size, SUVmax.
+ Distance metastases lesions: affected organs, size, SUV max.
+ Recurrence lesions:

18

FDG PET/CT was performed after last

treatment at least 3 months to eliminate false positive due to
inflammatory after treatments.
+ Other factors related to metastases and recurrence rates.


8
CHAPTER 3: RESULTS
3.1. THE ROLE OF

18

FDG PET/CT IN BREAST CANCER

STAGE DIAGNOSIS
3.1.1. Some characteristics of breast cancer patints before
treatment
Cancer patients in the study group had the lowest age of 28, the
highest was 87. The majority were aged 40-70 (72.8%). Under 40
years old and over 70 years old, the rate is low, accounting for 14.5%
and 12.7% respectively.
Each patient has only 1 tumor. Right breast tumors were found in
29/55 patients (52.7%) and left breast tumors in 26/55 patients
(47.3%). The most common primary tumor site is 1/4 in the upper
outer (42%), the upper inner and the lower outer sites are met with
36% and 18%, respectively.
The majority of patients have histology II (72.7%). Grade I had 4
patients (7.3%) and level III had 11 patients (20.0%).
The molecular subtype classification of breast cancer patients:
Luminal A 23.6%; Luminal B 34.5%, Her2 + overexpressed: 16.4%
and triple ER, PR and Her2 negative 25.5%.
Before 18FDG PET/CT scan, the almost of breast cancer patients
at T1 and T2 stage (85.5%). 14.5% of patients had a large breast
tumor invasive to the skin, chest wall.
56.4% of patients had not detected lymph nodes before PET/CT.
43.6% detected lymph nodes, of which N1 34.5%, N2-N3 9.1%.
Stage I: 7.3%, stage II accounts for the majority (72.7%), stages
IIIB and IIIC: 20.0%.


9
3.1.2. Diagnosis of tumors and lymph nodes on 18FDG PET/CT
In 55 patients, PET/CT detected primary tumors (100%), size

from 0.7cm to 7.6cm; 89.1% have size <5cm, average 2.87 ±1.46cm.
Table 3.7. Number of lymph nodes detected on 18FDG PET / CT
Lymph nodes on
Number of
Nodes/B Total number
18
FDG -PET/CT
patients
N
of nodes
No lymph nodes
19
0
0
16
1
16
12
2
24
4
3
12
With lymph nodes
36
2
4
8
2
5

10
Total
55
70
36/55 patients (65.5%) found lymph node (axillary lymph nodes,
internal mammary, supraclavicular nodes ...) with the number of 70
lymph nodes. The number of each patient is from 1 to 5 lymph nodes,
an average of 2 nodes/patient.
Table 3.10. Distance metastases detected on 18FDG PET/CT
Metastatic location
Number of patients Rate (%)
Lung
2
Bone
2
9
16.4
Lung + Bone
3
Contralateral breast

2

Distance metastases due to breast cancer in the study group were
found in 9/55 patients (16.4%), including 2 patients with lung
metastases, 2 patients with bone metastases, 2 patients with
metastases from contralateral breast, 3 patients both bone metastases
and lung metastases. Of the 9 patients with metastases detected, 4/40
patients (10.0%) in stage II and 5/11 (45.5%) in patients with stage
III before 18FDG PET/CT. No patients with stage I before 18FDG

PET/CT detected distance metastases.


10
3.1.3. Change of stage diagnosis on 18FDG PET/CT
Table 3.13. Change of T stage diagnosis after 18FDG PET/CT
Before 18FDG PET/CT
After 18FDG PET/CT
T
N0 of patients
T1
T2
T3
T4
T1
5
5
T2
42
3
34
5
T3
T4
8
8
Total
55
8
34

13
18
After FDG PET/CT scan, the T stage diagnossis (invasive)
changed in 8 patients:
3 patients before 18FDG PET/CT were T2, after 18FDG PET/CT
changed to T1 due to change in tumor size.
5 patients with T2 after 18FDG PET/CT changed to T4 due to skin
and/or chest wall invasion.
Table 3.14. Change of N stage diagnosis after 18FDG PET/CT
Before 18FDG PET/CT
After 18FDG PET/CT
N
N0 of patients
N0
N1
N2
N3
N0
31
18
9
2
2
N1
19
1
16
2
N2
2

1
1
N3
3
1
2
Total
55
19
25
4
7
The number of patients with lymph node-negative N 0 decreased,
and the number of patients with lymph node N1 and N3 increased due
to the detect of additional lymph nodes in the 18FDG PET/CT image.
18

FDG PET/CT changed the diagnosis of lymph node in 18/55
patients (32.7%), of which 16/55 patients (29.1%) had up-stage and
2/55 patients (3, 6%) with reduction stage.


11
The overall results after the 18FDG PET/CT changed the stage of
disease in 55 patients (according to the TNM classification of the
American Cancer Society AJCC- 2017) as follows:
Table 3.15. Change of TNM stage diagnosis after 18FDG PET/CT
Before

Stage TNM after 18FDG PET/CT

PET/CT
Stage

No of
Pt.

I

IIA

IIB

IIIA

IIIB

IIIC

IV

-

-

-

-

I

4

4

-

-

IIA

24

1

13

6

1

1

2

IIB

16

-

1

10

2

1

2

IIIA

0

IIIB

8

-

-

-

-

4

1

3

IIIC

3

-

-

-

-

-

1

2

IV

0

Total

55

0

0
5

14

16

7

4

9

- 4 patients with stage I did not change diagnosis after PET/CT.
- 24 patients with stage IIA before

18

FDG PET/CT, after 18FDG

PET/CT had stage changes in 11/24 patients (45.8%), of which 1
patient from T2 to T1 (tumor size = 1.4cm) changed from IIA to IA
and 10 patients (41.7%) increased the stage, including:
+ 2 patients changed to stage IV: 1 patient with lung metastases
(SUVmax = 5.99) and 1 patient with opposite side metastases (SUV max
= 3.69).
+ 6 patients wwith axillary lymph nodes changed to stage IIB
+ 1 patient with carina lymph nodes (1.6cm, SUV max= 8.7)
changed to stage IIIC.

+ 1 patient with invasive chest wall changed to stage IIIB.


12
- 16 patients with stage IIB before 18FDG PET/CT. After 18FDG
PET/CT changed stage in 6/16 patients (37.5%) including 1 patient
due to different tumor size, so from T2 to T1c and from IIB to IIA
stage. And 5 patients (31.2%) increased the stage, including:
+ 2 patients changed to stage IV: 1 patient with opposite side
metastases (SUVmax = 6.46) and 1 patient with multifocal bone
metastases.
+ 2 patients had invasive skin + chest wall, from T2 to T4,
changed to stage IIIB.
+ 1 patient found carina lymph nodes (SUV max=10.3), changed to
stage IIIC.
- 8 patients with stage IIIB before

18

FDG PET/CT, after

18

FDG

PET/CT, there were 4/8 patients (50%) with stage changes:
+ 3 patients changed to stage IV: 1 patient with lung metastases
(SUVmax = 3.1); 2 patients with lung and bone metastases.
+ 1 patient found subclavicular node (SUV max = 5.88) changed
from N2 to N3 and stage from IIIB to IIIC.

- 2 patients with stage IIIC before

18

FDG PET/CT, after

18

FDG

PET/CT detected 1 patient with lung metastases and bone metastases;
1 patient with multifocal bone metastases. Both cases are in stage IV
after 18FDG PET/CT.
A total 21/55 breast cancer patients (38.2%) had an increase in
stage after 18FDG PET/CT.
After 18FDG PET/CT, there were 21/55 patients (38.2%) with upstage, 2/55 patients (3.6%) with reduction stage. The rate of up-stage
in patients with stage II before PET/CT was 37.5% and in stage III
before PET/CT was 54.5%. 4 patients from stage II and 5 patients


13
from stage III were found metastases changed to stage IV, changing
the premary treatment method (16.4%).
3.1.4. 18FDG uptake characteristics of tumors, lymph nodes, and
metastases of breast cancer patients
3.1.4.1. 18FDG uptake characteristics of tumors
Table 3.17. 18FDG uptake (SUVmax) by tumors size
Tumor size
No of
Average

p
(cm)
patients
SUVmax
<2 (1)
17
4.14 ± 2.17
p1,2; p1,3 <0.05
(2)
2-5
32
8,70 ± 3.61
p2,3>0.05
>5 (3)
6
11.12 ± 7.69
Total:
55
7.56 ± 4.49
18
FDG uptake (SUVmax) of tumors is positively correlated with
the tumor size. The bigger tumor is, the higher SUV max is. Tumor
<2cm, the 18FDG has not increased much (SUV max = 4.14 ± 2.17).
Tumor size 2-5 cm 18FDG uptake doubled (SUVmax = 8.70 ± 3.61), p
<0.05.
Table 3.18. 18FDG uptake (SUVmax) of tumor related TNM
Stage
T
N
M

TNM
Total

T1 (1)
T2 (2)
T4 (3)
N0
N1-2-3
M1
M0
I (1)
II (2)
III (3)
IV (4)

No of Pt.
8
34
13
19
36
9
46
5
30
11
9
55

Average

SUVmax
2.84 ± 1.26
7.88 ± 3.87
9.62 ± 5.39
5.73 ± 4.05
8.52 ± 4.47
7.60 ± 4.74
7.35 ± 3.15
2.08 ± 0.60
7.67 ± 3.99
9.90 ± 5.80
7.35 ± 3.15
7.56 ± 4.49

p
p1,2; p1,3 <0,01
p2,3 >0,05
<0,05
>0,05
p1,2; p1,3;
p1,4 <0.01


14
SUVmax increases with the extent of tumor invasion, low in
patients with tumor at stage T1, (SUV max = 2.84 ± 1.26). When the
degree of invasion increased to T2, SUVmax increased (7.88 ± 3.87) (p
<0.01) and little changed with the increase of the next level of
invasion (p> 0.05).
18

FDG uptake in tumors in the group with metastatic lymph nodes
(including N1, N2 and N3 lymph nodes) increased (SUV max = 8.52 ±
4.47); significantly higher than in the group that did not detect lymph
node metastasis on 18FDG PET/CT (SUVmax = 5.73 ± 4.05), p <0.05.
18
FDG uptake of 5 patients at stage I was low, averaging 2.08 ±
0.60. In Stage II of 55 patients SUV max increased sharply to 7.67 ±
3.99, continued to increase the highest in stage III: SUV max = 9.90 ±
5.80.
Table 3.19. The influence of some pathological factors on the
18
FDG uptake
No of

Average

patients

SUVmax

I+II

44

6,8 ± 3,8

III

11

10,6 ± 5,8

Luminal A (1)

13

5,5 ± 3,5

(2)

19

6,8 ± 3,9

Her2+ (3)

9

7,2 ± 4,5

Triple negative (4)

14

10,9± 4,6

Ductal invasive

51

7,9 ± 4,5

Lobular and other

4

3,7 ± 0,6

Lesions

p

Histological grade:
<0.05

Molecular subtype:
Luminal B

p14, p24, p34
<0.05

Histopathology:
<0.01


15
11 patients with histology grade III had an SUV max =10.6 ± 5.8;
significantly higher than 44 patients with histology grade I-II
(p<0.05). Patients with ductal invasive type have significantly
higher

18

FDG uptake compared with invasive lobular type and

other type (p <0.01).
Triple subgroup ER, PR and Her2 negative had significantly
higher 18FDG uptake than the rest (p <0.05).
3.1.4.2. 18FDG uptake of tumors, lymph node and metastases
18

FDG uptake increases with lymph node size. Node <1cm with

SUVmax=2.38 ± 1.43; Lymph nodes 1-2cm have SUVmax = 3.64 ± 2.31
(p<0.01). Lymphs node with size>2cm,

18

FDG uptake

strongly,

SUVmax = 4.52 ± 1.25.
18

FDG uptake of lymph node in patients with N1, N2 group was

2.88 ±1.88; markedly lower than the

18

FDG uptake of N3 group

(when there is metastasis of subclavicular, supraclavicular lymph
nodes, etc.) (p <0.05).
3.2. THE ROLE OF PET/CT IN FINDING RECURRENCE
AND METASTASES
3.2.1. Some characteristics of the group of post-treatment cancer
patients
32/98 patients (32.7%) had

18

FDG PET/CT after 6 months of

finishing treatment of breast cancer. 15.3% were treated and the
patient's survival time was more than 5 years, the patient with the
longest time after finishing treatment was 15 years.


16
Table 3.25. Reason for indicating 18FDG PET/CT(n=98)
Reason for indicating
N0 of
Rate (%)
18
FDG PET/CT
patients
Post-treatment Evaluate
53

54.1
Replase, metastases on CT,
13
13.2
US, MRI
Replase, metastases on CT,
US, MRI and increase CA15.3
12
12.2
(>25 U/ml)
CA15.3 increated (>25 U/ml)
20
20.4
54.1% of patients had

18

FDG PET/CT scan to post-treatment

evaluate, detect metastatic recurrence. The remaining 45.9% took
18

FDG PET/CT scan because of signs of relapse, metastasis on

conventional imaging diagnosis (CT, US, MRI) and/or CA15.3
marker increased> 25 U/ml.
Table 3.28. Lymph node, recurrence, metastases detected
before PET/CT scan
Location of lesions

Number of

Rate (%)

patients
Bone

8

Bone + Liver

2

Liver

2

Lung

4

Brain

1

Metastases

Before

17

17.3

Lymph nodes

4

4

4.0

Recurrence

2

2

2.0

18

FDG PET/CT, clinically and by conventional imaging

diagnostics (CT, ultrasound, MRI, radiography...) detected distance


17
metastases in 18/98 patients (17.3%). Most common were bone
metastases: 10/98 patients (10.2%) and lung metastases 4/98 patients
(4.1%). Bedide, on the ultrasound also detected axillary nodes in 3

patients and supraclavicular node in 1 patient. 2 patients had local
recurrence lesions.
3.2.2. Detected recurrent and metastases on 18FDG PET/CT
From 98 treated breast cancer patients,

18

FDG PET/CT scan

detected lymph nodes in 34/98 patients (34.7%). The number of
increased uptake 18FDG lymph node detected in each patient from 1
to 6 nodes, the total number of lymph nodes detected in 34 patients is
82. The most common is mediastinal lymph nodes (34/82), followed
by axillary lymph nodes. Beside, there may be umbilical lymph
nodes, supraclavicular node, aortic straps node, inner mamary node...
Table 3.30. Detected recurrent and metastases on 18FDG PET/CT
in post-treatment breast cancer patients
Location

Number

Rate (%)

of patients

Distance
Metastases

Lung

20

20.4

Bone

22

22.5

Liver

8

8.2

Soft tissue

8

8.2

Brain

1

1.0

Other

7

7.1

12

12.3

Recurrence

In post-treatment breast cancer patients, 18FDG PET/CT detected
the most distance metastases in the bones (22.5%), followed by the
lungs (20.4%), in the soft tissue of chest wall 8.2%, in the liver 8.2%


18
and other locations 7/98 patients (7.1%). Local relapse has 12/98
cases (12.3%).
18
FDG PET/CT detected distance metastatic lesions in 17/17
(100%) patients, which were detected on conventional imaging and
detected further metastatic lesions in 27 other post-treatment breast
cancer patients. The total number of detected distance metastases is
44/98 (44.9%). The most are bone metastases and lung metastases;
17 patients with metastatic lesions of 2 or more organs. 12 patients
had a relapse. A total of 78 recurrent lesions and distance metastases
were detected in 54 patients.
Distance metastases due to breast cancer after treatment are found
much in lungs and bones. Also met metastases in liver, soft tissue of
chest wall and other locations. Brain metastases are detected only

when the tumor size is large and the level of 18FDG uptake is high.
18
FDG PET/CT detected relapses and distance metastases in 54
patients (55.1%), of which 2 patients had both local relapses and
distance metastases.
Table 3.32. The recurrence or metastases detected on
18

FDG PET / CT according to the indicative group
Number

Patients with

of

recurrent or

patients

metastases

53

19

35.8

13

13

100

12

11

Increased CA15.3 (>25 U/ml)

20

11

55.0

Total

98

54

55.1

Reason for indicating 18FDG
PET/CT post treatment
Evaluated post- treatment
Recurrence and metastases on CT,
US, MRI
Recurrence, metastases on CT,
US, MRI and increased CA15.3

Rate
(%)

91.7


19
In the group of patients, although there were no clinical
symptoms, in 18FDG PET/CT images detected 19/53 patients (35.8%)
with recurrence or distance metastases, increased

18

FDG

uptake

lesions. 13 patients with relapse and metastases detected by CT, US,
MRI were detected on PET/CT. Patients with suspected recurrence
and distance metastases were detected on

18

FDG PET/CT with

recurrent or distance metastases. The rate of recurrence and distance
metastases in the group suspected of recurrence through conventional
imaging diagnosis and increased serum CA15.3 was 11/12 patients
(91.7%); The group with high serum CA15.3 was 22/32 (68.7%).

CHAPTER 4: DISCUSSIONS
18

4.1. The role of FDG PET/CT in staging breast cancer
On 55 patients of group 1: before PET/CT scan, BC stage
according to TNM (based on clinical symptoms, X-ray, ultrasound,
MRI) was: stage I: 7.3%, stage II: 72.7%, stage III: 20%.
18

FDG PET/CT detected primary tumors in all cases (100%), sized

from 1.1cm to 7.6cm, average size was 2.87cm ± 1.46cm. 36/55
patients (65.5%) had lymph nodes with total of 70 nodes, sized from
0.5 - 2.4 cm, average size was 1.15 ± 0.4cm. About 1/3 nodes
(32.8%) had size smaller than 1cm, 62.9% had size from 1-2cm, only
4.3% had size above 2cm.
18

FDG PET/CT detected distance metastases in 9 more patients

(16.4%): 2 with lung metastases, 2 with bone metastases, 3 with lung
and bone metastases, and 2 with opposite breast metastases.
18

FDG PET/CT showed pros over other imaging methods in

detecting lymph nodes like supraclavical nodes, internal mammary
nodes, lung and bone metastases. PET/CT had low sensitivity with

20
brain metastases. In patients with high risk such as inflammatory type
BC (T4d) or local advanced BC, 18FDG PET/CT had very high value
in detecting distance metastases. Other study also showed the role of
18

FDG PET/CT with BC stage IIB (T2N1/T3N0).
After underwent

18

FDG PET/CT, 21/55 patients (38.2%) had

increased stage. In 24 patients with stage IIA before scan, after scan
10/24 patients had increased stage (41.7%). In 16 patients with stage
IIB before scan, after scan 5/16 patients had increased stage (31.2%).
In 8 patients with stage IIIB before scan, after scan 4/8 patients had
increased stage. In 2 patients with stage IIIC before scan, after scan 1
patient had bone and lung metastases; 1 patient had multiple bone
metastases. Both patients were considered stage IV. 4 patients in
stage II and 5 patients in stage III were considered stage IV because
of metastases detecting, and also had their treatments plan
changed.18FDG PET/CT had high value in N1 stage nodes.
4.1.1. 18FDG uptake in breast cancer
Highest SUVmax in our patients was 22.97, average was 7.56 ±
4.49. SUVmax of tumors increased according to tumors size.
Especially in tumor bigger than 2cm, SUV max was much higher
(p<0.01).
There is an association of SUVmax with histology and
histopathology of breast cancer. Invasive ductal carcinoma breast

cancer had higher SUVmax than Tubular carcinoma breast cancer.
SUVmax also had correlation with proliferation biomarker Ki67. 18FDG
uptake (SUVmax) is higher in triple negative breast cancer.


21
4.2. The role of

18

FDG PET/CT in detecting recurrence and

distance metastases in post-treatment patients
Local recurrence or distance metastases occur in more than 35%
post-treatment patients. Each year, there are 2 million new BC
patients and more than 30% BC patients have local recurrence or
distance metastases in 15 year after treatments.
Early and accurate detection of recurrence and metastases lesions
in BC patients has high value in re-staging and choosing follow up
treatments. Local recurrence can be treated with surgery or
radiotherapy; distance metastases can be treated with chemotherapy
or palliative care. PET/CT is an effective whole body imaging
methods for detecting recurrence, metastases in cancer in general and
BC cancer specific with accuracy above 90% in BC patients.
Before, we diagnoses recurrence based on clinical symptoms and
other conventional imaging methods, laboratory tests. 18FDG PET/CT
has pros in diagnoses of recurrence lesion over other imaging
methods with higher sensitivity and specificity, especially in patients
have high tumor marker result. Other study showed that in patients
without clinical symptoms but have high bio marker, 18FDG PET/CT

can detect metastases with accuracy upto 87-90% when other
imaging methods only have accuracy about 50-78%.
General guidelines recommend post-treatment

18

FDG PET/CT

scan in patient with pre-treatment stage from II to IIIB, and patient
with inflammatory BC. Because in these groups, metastases can be
detect with highest rate and thought changing the treatment of choice.
In our study, 18FDG PET/CT found distance metastases in 34/98
patients (34.7%).

18

FDG PET/CT detected all metastases that were

already detected on other methods. Besides that, 18FDG PET/CT also


22
detected distance metastases in 27 more patients after treatments. In
total, there were 44/98 patients with distance metastases detected
after treatment (44.9%). Highest rate metastasis was bone metastases
(22.5%), follow by lung metastases (20.4%), thoracic wall metastases
(8.2%), hepatic (8.2%) and other metastases (7.1%).
There were 66 distance metastases lesions with increased 18FDG
absorption that were detected in 44 patients. And besides, recurrence
lesions were detected in 12/98 patients (12.3%). In those patients,

there were 2 patients had both local recurrence and distance
metastases.
CONCLUSIONS
1. FDG uptake characteristic and the role of 18FDG PET/CT in
breast cancer staging before treatment:
- 18FDG PET/CT đã phát hiện u nguyên phát ở 100% bệnh nhân
ung thư vú với kích thước từ 1,1 đến 7,6cm; phát hiện hạch được ở
36/55 (65,5%) bệnh nhân với số lượng 70 hạch với kích thước 0,52,4cm; phát hiện di căn xa ở 9/55 (16,4%) bệnh nhân.
- Sau chụp 18FDG PET/CT, 21/55 (38,2%) bệnh nhân tăng giai
đoạn, trong đó 15/40 (37,5%) bệnh nhân ở giai đoạn II và 6/11 bệnh
nhân (54,5%) ở giai đoạn III khi chưa có kết quả chụp PET/CT.
Không có thay đổi ở bệnh nhân giai đoạn I trước và sau chụp
PET/CT. Kết quả 18FDG PET/CT đã làm thay đổi chiến thuật điều trị
ở 9/55 bệnh nhân (16,4%).
- Trên hình ảnh 18FDG PET/CT cho thấy có sự tăng hấp thu 18FDG
ở u và hạch của bệnh nhân ung thư vú, SUV max trung bình của u là
7,55 ± 4,32; SUVmax trung bình của hạch là 3,49±2,40. Mức độ hấp
thu 18FDG tăng theo kích thước u, giai đoạn bệnh. SUV max của u ở
bệnh nhân có hạch N1-2-3 cao hơn ở bệnh nhân chưa có hạch N 0
18