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The role of 18FDG PET/CT in diagnosis of stage, recurrence, metastases in breast cancer patients pre and post treatment

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To evaluate the role of PET/CT in staging diagnosis in pre-treatment breast cancer patients and finding recurrence lesions, metastases in post-treatment breast cancer patients.

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THE ROLE OF 18FDG PET/CT IN DIAGNOSIS OF STAGE, RECURRENCE, METASTASES IN BREAST CANCER

PATIENTS PRE- AND POST-TREATMENT

Nguyen Trong Son 1 ; Nguyen Danh Thanh 2

SUMMARY

Objectives: To evaluate the role of PET/CT in staging diagnosis in pre-treatment breast cancer patients and finding recurrence lesions, metastases in post-treatment breast cancer patients Subjects and methods: 55 pre-treatment breast cancer patients were performed

18

FDG PET/CT for initial staging diagnosis and 98 breast cancer patients underwent mastectomy, radiotherapy and/or chemotherapy with clinical symptoms or radiologic findings or rising levels of tumor markers (CA15.3; CEA) had been performed 18 FDG PET/CT to assess the recurrence, metastases Results: 18 FDG PET/CT gave result of increased stage in 21/55 patients (38.2%) included: 15/40 patients (37.5%) in stage II and 6/11 patients (54.5%) in stage III There was no change in patients with stage I These results also changed treatment of choice in 9/55 patients (16.4%) In 98 post-treatment patients, 18 FDG PET/CT detected lymph nodes with increased SUV max in 34/98 patients (34.7%), detected recurrence and distance metastases in 54 patients (55.1%): 12 patients had local recurrence (12.3%), of which 2 patients with local recurrence and distance metastases Bone metastases rate was 22.5%; lung metastases rate was 20.4%; thoracic wall metastases rate was 8.2%; hepatic metastases rate was 8.2% and other metastases rate was 7.1% Conclusion: 18 FDG PET/CT scan effectively detected axillary and extraaxilary nodes, distance metastases, it had great value in stage diagnosis for pre-treatment breast cancer and for following-up, detection of recurrent and metastases in post-treatment breast cancer patients

* Keywords: Metastatic breast cancer; Recurrence; 18 FDG PET/CT

INTRODUCTION

The diagnosis of breast cancer is based

on clinical symptoms, histology and diagnosis

imaging such as mammography, ultrasound,

computed tomography scan (CT-scan)

and magnetic resonance imaging (MRI)

Positron emission tomography/computed

tomography with

fluorine-18-fluoro-deoxyglucose (18FDG PET/CT) can detect

early changes of metabolic shift of disease,

even before physiological and anatomical changes In patients with breast cancer,

18FDG PET/CT had been demonstrated in accurate diagnosis of tumor location, allows to find axillary and extraaxillary lymphatic node (upper and lower clavicular nodes, inner mammary nodes), thoracic and abdominal metastases, bone metastases,

so it can help to evaluate pre-treatment breast cancer stage

1 Viet Duc Hospital

2 103 Military Hospital

Corresponding author: Nguyen Trong Son (ntrongson@yahoo.com)

Date received: 01/10/2019

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18FDG PET/CT also has high accuracy

rate, sensitivity (Se) and specificity (Sp) in

follow up scan to find post-treatment

recurrence and metastases 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 patient has no clinical symptoms

In Vietnam, nowadays, it had a few

studies about value of 18FDG PET/CT in

patients with breast cancer However, this

is not yet a systematic, fully documented

about stage diagnosis value of 18FDG

PET/CT

Therefore, this study was carried out

with following objectives: To evaluate the

in pre-treatment breast cancer patients

and for finding recurrence lesions, metastases

in post-treatment breast cancer patients

SUBJECTS AND METHODS

1 Subjects

- Group 1: 55 patients diagnosed with

breast cancer by histopathology were

underwent 18FDG PET/CT scan for

pre-treatment staging diagnosis Patients'

staging according to TNM classification of

American Joint Committee on Cancer (AJCC)

(2017) based on clinical examinations,

CT-scan and MRI

- Group 2: 98 post-treatments (mastectomy

+/- radiotherapy +/- chemotherapy) breast

cancer patients, underwent 18FDG PET/CT

or patients had clinical symptoms, with

recurrence lesions and metastases detected

on other conventional imaging methods or

with high tumor markers concentrations

(CEA, CA15.3) or to post-treatment

follow-up patients

2 Methods

- Study design: Non-control prospective clinical study, cross-sectional description with convenience sampling

- 18FDG PET/CT was processed according

to American College of Radiology (ACR) and European Association of Nuclear Medicine (EANM) guidelines [1, 2]

- 18FDG was produced in Cyclotron Center of 108 Military Central Hospital Used dose: 0.15 mCi/kg (5.55 MBq/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

The results were analyzed by both nuclear medicine doctors and radiologists: Identified lesions (tumor, lymph node, distance metastases) with increased

18FDG uptake on PET/CT (SUVmax > 2,5) The staging of patients was compared between pre- and post-FDG PET/CT scan

In post-treatment cancer patient group,

18FDG PET/CT was performed after last treatment at least 3 months to eliminate false positive due to inflammatory after treatments

RESULTS AND DISCUSSION

1 The role of 18 FDG PET/CT in staging breast cancer

Before 18FDG PET/CT scan, the almost

of breast cancer patients were at T1 and T2 stage (85.5%) 14.5% of patients had a large breast tumor with invasion to the skin, chest wall 43.6% of patients

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detected lymph nodes, of which N1 in

34.5% of patients and N2 - N3 in 9.1% of

patients Stage I was in 7.3% of patients

and stage II accounted for the majority

(72.7%), stages IIIB and IIIC were 20.0%

On 18FDG PET/CT detected primary

tumors in 55/55 patients (100%); tumor

size 0.7 - 7.6 cm; average tumor size was

2.87 ± 1.46 cm

36/55 patients (65.5%) were found

lymph node (axillary lymph nodes, inner

mammary, supraclavicular nodes ) with

the total number of 70 lymph nodes

Distance metastases 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 with both bone metastases and lung metastases

Of the 9 patients with metastases detected, 4/40 patients (10.0%) were in stage II and 5/11 patients (45.5%) were in stage III before 18FDG PET/CT No patients with stage I before 18FDG PET/CT were detected distance metastases

Before 18 FDG PET/CT After 18 FDG PET/CT

The number of patients with lymph node-negative (N0) decreased, and the number

of patients with lymph node N1 and N3 increased due to the detection of additional lymph nodes in the 18FDG PET/CT image 18FDG PET/CT changed the diagnosis of lymph node stage in 18/55 patients (32.7%), of which 16/55 patients (29.1%) had up-stage and 2/55 patients (3,6%) with reduction up-stage

Before PET/CT Stage TNM after 18 FDG PET/CT

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- 4 patients with stage I did not change

diagnosis after PET/CT

- 24 patients with stage IIA before

18FDG 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

was 1.4 cm) 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 and 1 patient

with contralateral side metastases

+ 6 patients with axillary lymph nodes

changed to stage IIB

+ 1 patient with carina lymph nodes

changed to stage IIIC

+ 1 patient with invasive chest wall

changed to stage IIIB

- 16 patients with stage IIB before 18FDG

PET/CT, after 18FDG PET/CT changed

stage in 6/16 patients (37.5%), including

1 patient from T2 to T1c and so from IIB to

IIA stage, other 5 patients (31.2%) increased

the stage, including:

+ 2 patients changed to stage IV: 1 patient

with opposite side metastases and 1 patient

with multifocal bone metastases

+ 2 patients had invasive skin + chest

wall, from T2 to T4 and so that they changed

to stage IIIB

+ 1 patient found carina lymph node,

changed to stage IIIC

- 8 patients with stage IIIB before

18FDG PET/CT, after 18FDG PET/CT,

there were 4/8 patients (50%) with stage

changes:

+ 3 patients changed to stage IV:

1 patient with lung metastases; 2 patients with lung and bone metastases

+ 1 patient found subclavicular node, changed from N2 to N3 and stage from IIIB

to IIIC

- 2 patients with stage IIIC before 18FDG PET/CT, after 18FDG PET/CT detected

1 patient with lung metastases and bone metastases; 1 patient with multifocal bone metastases Both cases were in stage IV after 18FDG PET/CT

After 18FDG PET/CT, there were 21/55 patients (38.2%) with up-stage, 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 from stage III were found metastases and changed to stage IV, so that they had to change the primary treatment method (16.4%)

18FDG PET/CT showed advantages over other imaging methods in detecting lymph nodes like supraclavical nodes, inner mammary nodes, lung and bone metastases 18FDG PET/CT had low sensitivity with brain metastases In patients with high risk such as inflammatory type breast cancer (T4d) or local advanced breast cancer, 18FDG PET/CT had high value

in detecting distance metastases Other study also showed the role of 18FDG PET/CT with breast cancer stage IIB (T2N1/T3N0) [3, 4]

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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 post-treatment patients Each

year, there are more 2 million new breast

cancer patients and more than 30% of

breast cancer patients have local recurrence

or distance metastases in 15 years after

treatments [5, 6]

In the group of 98 post-treatment

cancer patients, 54.1% of patients had

18FDG PET/CT scan to evaluate and

detect metastatic recurrence The remaining

(45.9%) took 18FDG PET/CT scan because

of signs of relapse, metastasis on conventional

imaging diagnosis (CT, ultrasound, MRI)

and/or CA15.3 marker increased > 25 U/mL

Before 18FDG PET/CT, clinically and/or

by conventional imaging diagnostics (CT,

ultrasound, MRI, radiography ) detected

distance metastases in 17/98 patients

(17.3%) Most common were bone

metastases: 10/98 patients (10.2%) and

lung metastases 4/98 patients (4.1%) On

the ultrasound also detected axillary

nodes in 3 patients and supraclavicular

node in 1 patient; 2 patients had local

recurrence lesions

18FDG PET/CT scan detected lymph

nodes in 34/98 patients (34.7%) The

number of increased uptake 18FDG lymph

node detected in each patient 1 - 6 nodes,

the total number of lymph nodes detected

in 34 patients was 82 The most common

was mediastinal lymph nodes (34/82 patients),

followed by axillary lymph nodes

Table 3: Detected recurrent and

metastases on 18FDG PET/CT in

post-treatment breast cancer patients

Location Number of

patients

Rate (%)

Distance metastases

18FDG PET/CT detected distance metastatic lesions in 17/17 patients (100%), 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 was 44/98 patients (44.9%) The most were

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 were found much

in lungs and bones Brain metastases were detected only when the tumor size was large and the level of 18FDG uptake was high

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

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Table 4: The recurrence or metastases detected on 18FDG PET/CT according to the

indicative group

Reason for indicating

post-treatment 18 FDG PET/CT

Number of patients

Patients with recurrent or metastases

Rate (%)

Recurrence, metastases on CT, ultrasound, MRI and

91.7

Patients with suspected recurrence

and distance metastases were detected

on 18FDG 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%) and the group

with high serum CA15.3 was 22/32 (68.7%)

Early and accurate detection of recurrence

and metastases lesions in breast cancer

patients has high value in re-staging and

choosing 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 breast cancer in

particular with accuracy above 90% [7, 8]

PET/CT has advantages in diagnosis

of recurrence lesions over other imaging

methods with higher sensitivity and specificity,

especially in patients have high concentration

of serum tumor marker In patients without

clinical symptoms but have high biomarker,

18FDG PET/CT can detect metastases

with accuracy up to 87 - 90% while other imaging methods only have accuracy about 50 - 78%

General guidelines recommend post-treatment 18FDG PET/CT scan in patient with pre-treatment stage from II to IIIB, and patient with inflammatory breast cancer

Because in these groups, metastases can

be detected with the highest rate and thought changing the treatment of choice

In our study, 18FDG PET/CT detected all metastases that were already detected

on other methods

CONCLUSIONS

18FDG PET/CT could detect primary tumor in 100% of breast cancer patients, with size 1.1 - 7.6 cm; detected lymph nodes in 36/55 patients (65.5%) with total

of 70 nodes, size from 0.5 - 2.4 cm;

detected distance metastases in 9/55 patients: 2 patients (3.6%) with lung

metastases, 3 patients (5.5%) with lung and bone metastases, 2 patients (3.6%) with bone metastases and 2 patients (3.6%) with contralateral side metastases

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Compare to clinical based and other

methods based cancer stage, 18FDG PET/CT

gave result of increased stage in

21/55 patients (38.2%) included:

15/40 patients (37.5%) in stage II and

6/11 patients (54.5%) in stage III There

was no change in patients with stage I

These results helped to change treatment

of choice in 9/55 patients (16.4%)

In 98 post-treatment patients, 18FDG

PET/CT detected lymph nodes with increased

SUVmax in 34/98 patients (34.7%) with total

of 82 nodes 18FDG PET/CT also detected

recurrence and distance metastases in 54

patients (55.1%): 12 patients had local

recurrence (12.3%); 2 patients with local

recurrence and distance metastases

Bone metastases rate was 22.5%; lung

metastases rate was 20.4%; thoracic wall

metastases rate was 8.2%; hepatic

metastases rate was 8.2% and other

metastases rate was 7.1% 17 patients

(17.3%) had metastases in at least 2 organs

In post-treatment follow up group,

13/53 patients (24.5%) had metastases

lymph nodes with increased SUVmax and

19/53 patients (35.8%) had recurrence or

distance metastases In patients with

increased CA15.3, 16/32 patients (50%)

had metastases lymph nodes and

22/32 patients (68.7%) had recurrence and

distance metastases

REFERENCES

1 ACR ACR-SPR practice parameter for

perfoming 18FDG PET/CT in oncology Resolution

2016, 25, pp.1-9

2 18FDG PET/CT EANM procedure guideline

for tumour imaging: Version 2.0 Eur J Nucl Med Mol Imaging 2015, 42, pp.328-354

3 Segaert I, Mortaghy R Additional value

of PET/CT in staging of clinical stage IIB and III breast cancer Breast J 2010, 16, pp.617-662

4 Lebon V, Alberini J.L, Pierga J.Y Rate

of distant metastases on 18FDG PET/CT at initial staging of breast cancer: Comparison

of women younger and older than 40 years

J Nucl Med 2017, 58, pp.252-257

5 Cochet A, David S, Moodie K et al

The utility of 18FDG PET/CT for suspected recurrent breast cancer: Impact and prognostic stratification Cancer Imaging 2014, 14, p.13

6 Piva R, Ticconi F, Ceriani V Comparative

diagnostic accuracy of FDG PET/CT for breast cancer recurrence Breast Cancer - Targets and Therapy 2017, 9, pp.461-471

7 Gaeta C.M, Sher A.C, Kohan A et al

Recurrent and metastatic breast cancer PET, PET/CT, PET/MRI: FDG and new biomarkers The Quarterly J of Nucl Med and Mol Imaging

2013, 57, pp.352-366

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