VIETNAM MILITARY MEDICAL UNIVERSITYNGUYEN TRONG SON STUDY ON 18FDG UPTAKE CHARACTERISTICS, THE ROLE OF PET/CT IN DIAGNOSIS OF STAGE, RECURRENCE, METASTASES IN BREAST CANCER PATIENTS BEFO
Trang 1VIETNAM 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
Trang 2Supervisors:
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
Trang 31 Nguyen Trong Son, Nguyen Danh Thanh (2019) The role of
18FDG 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
18FDG PET/CT stage diagnosis in 55 breast cancer patients J.
of Community Medicine, 4 (51): 48-52.
Trang 4Breast cancer (BC) is the most common female cancer, withhigher rate of morbidity in Europe and American, lower in Asia andAfrica In Viet Nam, BC is the most common female cancer withmorbidity rate is increasing each year
The diagnosis of BC is based on clinical history, histology anddiagnosis imaging such as mammography, ultrasound, CT scan,MRI SPECT (Single Photon Emission Computed Tomography) andPET (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 ofdisease, even before physiological and anatomical changes Inpatients with BC, 18FDG PET/CT allows us to find axillary node,extraaxillary locoregional node (supraclavicular or internal mammarynodes), thoracic and abdominal metastases, bone metastases, evaluatecancer stage before treatment After 18FDG PET/CT, changed thestage diagnosis in 1/3 of patients and treatment tactics was changed
in 1/6 of patients with BC
18FDG PET/CT also has high accuracy rate, sensitivity (Se) andspecificity (Sp) in follow up scan to find recurrence, metastases aftertreatment Especially when patient with clinical symptoms ofrecurrence or high serum concentration of tumor markers but has noabnormal sign in other conventional imaging method, or even whenpatients has no clinical symptoms
In Vietnam nowadays, it had a few studies about value of 18FDGPET/CT in patients with BC But there didn't have a systematic studyabout characteristics of 18FDG uptake in tumors, recurrence anddistance metastases lesions; axilary nodes, extraaxilary nodes; stagediagnosis value of 18FDG PET/CT, at which clinical stage 18FDGPET/CT should be intiated? And which the role of PET/CT forfollow up?
Trang 5So we did our study about "Study on 18FDG uptakecharacteristics, the role of PET/CT in diagnosis of stage, recurrence,metastases in breast cancer patients before and post treatment" withfollowing research objectives:
1/ Study on 18FDG uptake characteristics, the role of PET/CT indiagnosis of stage in breast cancer patients pre-treatment
2/ Evaluate the role of 18FDG PET/CT in finding recurrencelesions and metastases in breast cancer patients post-treatment
- New contributions
The results of thesis confirmed the value of the 18FDG PET/CTmethod in the staging diagnosis of breast cancer patients: tumordetection at the rate of 100% of the patients, detected nodalmetastases on 36/55 patients (65.6%) and metastases on 9/55 patients(16.4%) 18FDG PET/CT method changed the diagnosis, wereupstaging TNM of 21/55 patients (38.2%), which is the basis forphysicians to select the appropriate treatment method Treatmenttactics was changed in 9/55 patients (16.4%)
The thesis demonstrated the role of 18FDG PET/CT in lymph nodedetection, distance metastases, local recurrence of tumor in posttreatment breast cancer patients
The thesis has identified the 18FDG uptake characteristics oftumors, nodes, and distance metastases of breast cancer patients, therelations between SUVmax of primary tumor with lymph node status,distance metastases, tumor size and histological grade,histopathological type It also found the relations between SUVmax ofmetastatic nodules with location and lymph node size
- The dissertation structure:
The dissertation consists of 118 pages, including: Introduction (2pages), 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, 138references (21 Vietnamese and 117 English), and Index
Trang 6Conventional imaging methods such as CT, MRI often hasdifficulty and easily give false negative when metastases and lymphnodes are size smaller than 1cm 18FDG PET/CT have higher value of
Se and Sp in cancer staging pre and post-treatments compare toconventional CT scan 18FDG PET/CT also has about 10-15% moreaccurate compare to PET scan alone in cancer staging diagnosis
Se and Sp value of 18FDG PET/CT in BC diagnosis is 80-96% and83-100% respectively 18FDG PET/CT Sp value in distinguishingbetween benign and malign lesions is about 90%
Using 18FDG PET/CT can detect lymph nodes, which sizes are notbig enough to be found in conventional CT scan 18FDG uptake inPET/CT allows us to detect axillary nodes and lymph nodes group III
as supraclavicular node, inner mammary node
18FDG PET/CT is prefer to evaluated local and distancemetastases in advanced stage of BC It was helpful for detectingoccult non-symptoms metastases lesions, which can be missed inconventional imaging methods
18FDG PET/CT has important role in determining the stage ofdisease for patients in stage IIB (T2N1, T3N0) and IIIA (T3N1)
Trang 7Beside the role of staging diagnosis, the 18FDG uptake by aprimary tumor also has high value in prognosis Patient who hashigher 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 localrecurrence and post-treatment follow up MRI is also used todistinguish between scars and recurrence lesions, or to diagnosecomplications 18FDG PET/CT has high value in detecting abnormalafter radiotherapy treatment or mammoplasty complications.Locations with high rate of recurrent post-treatments are thoracicwall and upper clavical nodes 18FDG PET/CT is useful for detectinglocal recurrence and distance metastases post-treatments
CHAPTER 2: SUBJECTS AND METHODS
18FDG 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 recurrencelesions and metastases detected on other conventional imagingmethods as mammography, CT MRI, ultrasound, bone scintigraphy
Trang 8+ Subgroup 3: patients with high tumor markers concentrations(CEA, CA15.3).
- Exclude patients who are pregnant or breastfeeding; Patients atrisk of near death due to other serious illnesses
PET/CT was taken at Viet Duc Hospital, Bachmai Hospital and Khospital from 2013 to march 2019
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 breastcancer 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 lobularcarcinoma
+ Clinical subtype: Luminal A, Luminal B, Her2-positive, triplenegative
+ Tumor markers test: CEA (normal:<4.3ng/ml), CA15.3(normal: <25 U/ml)
- TNM staging before 18FDG PET/CT according to AmericanJoint Committee on Cancer (AJCC - 2017)
Trang 9In 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 18FDGPET/CT
- Tumor markers test: CEA, CA15.3
2.2.2.2 18 FDG PET/CT procedure
18FDG PET/CT was processed according to American College ofRadiology (ACR) and European Association of Nuclear Medicine(EANM) guidelines
- Radiopharmaceutical and PET/CT systems:
+ Radiopharmaceutical: solution-based 18FDG D-glucose) was produced in Cyclotron center of Vietnam MilitaryCentral Hospital 108 and Institute of Nuclear Science andTechnology
(2-flouro-2-deoxy-Used dosage: 0.15mCi/kg (5.55MBq/kg); injected through venoussystem 45 minutes before scan process
+ PET/CT system: GE PET/CT Discovery ST4 system, SiemensPET/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, lymphnodes, and distance metastases lesions
+ All images were recorded in CDRom, and were analyzed by
two nuclear medicine doctors, using TRUE D software system
Trang 10+ The 18FDG PET/CT image is firstly analyzed qualitatively:location, affected organ Next step determines the size, SUVmax oftumors, lymph nodes, distance metastase lesions
+ Evaluation of lymph node metastases: number of lymph nodes,supraclavicular lymph nodes, inner mammary lymph nodes newlydetected on 18FDG PET/CT
+ Metastases and recurrence lesions: number, location of lesions,
18FDG uptake SUVmax
- Measurements on 18 FDG 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 lymphnodes
In patients group 2: breast cancerpatients after treatment
+ Lymph nodes: Number, location, size, SUVmax
+ Distance metastases lesions: affected organs, size, SUVmax.+ Recurrence lesions: 18FDG PET/CT was performed after lasttreatment at least 3 months to eliminate false positive due toinflammatory after treatments
+ Other factors related to metastases and recurrence rates
Trang 11CHAPTER 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, thehighest was 87 The majority were aged 40-70 (72.8%) Under 40years 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 in29/55 patients (52.7%) and left breast tumors in 26/55 patients(47.3%) The most common primary tumor site is 1/4 in the upperouter (42%), the upper inner and the lower outer sites are met with36% and 18%, respectively
The majority of patients have histology II (72.7%) Grade I had 4patients (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 breasttumor 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%), stagesIIIB and IIIC: 20.0%
Trang 123.1.2 Diagnosis of tumors and lymph nodes on 18 FDG PET/CT
In 55 patients, PET/CT detected primary tumors (100%), sizefrom 0.7cm to 7.6cm; 89.1% have size <5cm, average 2.87 ±1.46cm
Table 3.7 Number of lymph nodes detected on 18 FDG PET / CT
an average of 2 nodes/patient
Table 3.10 Distance metastases detected on 18 FDG PET/CT
Metastatic location Number of patients Rate (%)
Trang 13III before 18FDG PET/CT No patients with stage I before 18FDGPET/CT detected distance metastases.
3.1.3 Change of stage diagnosis on 18 FDG PET/CT
Table 3.13 Change of T stage diagnosis after 18 FDG PET/CT
Before 18 FDG PET/CT After 18 FDG PET/CT
Table 3.14 Change of N stage diagnosis after 18 FDG PET/CT
Before 18 FDG PET/CT After 18 FDG PET/CT
Trang 1418FDG PET/CT changed the diagnosis of lymph node in 18/55patients (32.7%), of which 16/55 patients (29.1%) had up-stage and2/55 patients (3, 6%) with reduction stage.
The overall results after the 18FDG PET/CT changed the stage ofdisease in 55 patients (according to the TNM classification of theAmerican Cancer Society AJCC- 2017) as follows:
Table 3.15 Change of TNM stage diagnosis after 18 FDG PET/CT
- 4 patients with stage I did not change diagnosis after PET/CT
- 24 patients with stage IIA before 18FDG PET/CT, after 18FDGPET/CT had stage changes in 11/24 patients (45.8%), of which 1patient from T2 to T1 (tumor size = 1.4cm) changed from IIA to IAand 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 (SUVmax
= 3.69)
+ 6 patients wwith axillary lymph nodes changed to stage IIB
Trang 15+ 1 patient with carina lymph nodes (1.6cm, SUVmax= 8.7)changed to stage IIIC.
+ 1 patient with invasive chest wall changed to stage IIIB
- 16 patients with stage IIB before 18FDG PET/CT After 18FDGPET/CT changed stage in 6/16 patients (37.5%) including 1 patientdue to different tumor size, so from T2 to T1c and from IIB to IIAstage And 5 patients (31.2%) increased the stage, including:
+ 2 patients changed to stage IV: 1 patient with opposite sidemetastases (SUVmax = 6.46) and 1 patient with multifocal bonemetastases
+ 2 patients had invasive skin + chest wall, from T2 to T4,changed to stage IIIB
+ 1 patient found carina lymph nodes (SUVmax=10.3), changed tostage IIIC
- 8 patients with stage IIIB before 18FDG PET/CT, after 18FDGPET/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 (SUVmax = 5.88) changedfrom N2 to N3 and stage from IIIB to IIIC
- 2 patients with stage IIIC before 18FDG PET/CT, after 18FDGPET/CT detected 1 patient with lung metastases and bone metastases;
1 patient with multifocal bone metastases Both cases are in stage IVafter 18FDG PET/CT
A total 21/55 breast cancer patients (38.2%) had an increase instage after 18FDG PET/CT
After 18FDG PET/CT, there were 21/55 patients (38.2%) with stage, 2/55 patients (3.6%) with reduction stage The rate of up-stage