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.
Jourrnal of military pharmaco-medicine n09-2019 THE ROLE OF 18FDG PET/CT IN DIAGNOSIS OF STAGE, RECURRENCE, METASTASES IN BREAST CANCER PATIENTS PRE- AND POST-TREATMENT Nguyen Trong Son1; Nguyen Danh Thanh2 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 18 rising levels of tumor markers (CA15.3; CEA) had been performed FDG PET/CT to assess the 18 recurrence, metastases Results: 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 18 choice in 9/55 patients (16.4%) In 98 post-treatment patients, FDG PET/CT detected lymph nodes with increased SUVmax 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 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 18 was 8.2% and other metastases rate was 7.1% Conclusion: 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 18 * Keywords: Metastatic breast cancer; Recurrence; 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-fluorodeoxyglucose (18FDG PET/CT) can detect early changes of metabolic shift of disease, even before physiological and anatomical changes In patients with breast cancer, 18 FDG 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 Viet Duc Hospital 103 Military Hospital Corresponding author: Nguyen Trong Son (ntrongson@yahoo.com) Date received: 01/10/2019 Date accepted: 27/11/2019 299 Jourrnal of military pharmaco-medicine n09-2019 18 FDG 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 role of 18FDG PET/CT in staging diagnosis in pre-treatment breast cancer patients and for finding recurrence lesions, metastases in post-treatment breast cancer patients SUBJECTS AND METHODS Subjects - Group 1: 55 patients diagnosed with breast cancer by histopathology were underwent 18FDG PET/CT scan for pretreatment 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 300 (CEA, CA15.3) or to post-treatment followup patients 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 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 18 FDG 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, 18 FDG PET/CT was performed after last treatment at least months to eliminate false positive due to inflammatory after treatments RESULTS AND DISCUSSION The role of 18FDG PET/CT in staging breast cancer Before 18FDG PET/CT scan, the almost of breast cancer patients were at T 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 Jourrnal of military pharmaco-medicine n09-2019 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 patients with lung metastases, patients with bone metastases, patients with metastases from contralateral breast, patients with both bone metastases and lung metastases Of the 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 Table 1: Change of N stage diagnosis after 18FDG PET/CT Before 18 FDG PET/CT After 18 FDG PET/CT N Number of patients N0 N1 N2 N3 N0 31 18 2 N1 19 16 - N2 - 1 N3 - - 55 19 25 Total 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 upstage and 2/55 patients (3,6%) with reduction stage Table 2: Change of TNM stage diagnosis after 18FDG PET/CT Before PET/CT Stage TNM after 18 FDG PET/CT Number of patients I IIA IIB IIIA IIIB IIIC IV I 4 - - - - - - IIA 24 13 1 IIB 16 - 10 2 IIIA IIIB - - - - IIIC - - - - - IV Stage Total 55 0 14 16 301 Jourrnal of military pharmaco-medicine n09-2019 - patients with stage I did not change diagnosis after PET/CT - 24 patients with stage IIA before FDG PET/CT, after 18FDG PET/CT had stage changes in 11/24 patients (45.8%), of which 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: 18 + patients changed to stage IV: patient with lung metastases and patient with contralateral side metastases + patients with axillary lymph nodes changed to stage IIB + patients changed to stage IV: patient with lung metastases; patients with lung and bone metastases + patient found subclavicular node, changed from N2 to N3 and stage from IIIB to IIIC - patients with stage IIIC before 18FDG PET/CT, after 18 FDG PET/CT detected patient with lung metastases and bone metastases; patient with multifocal bone metastases Both cases were in stage IV after 18FDG PET/CT After 18 FDG PET/CT, there were + patient with carina lymph nodes changed to stage IIIC 21/55 patients (38.2%) with up-stage, + patient with invasive chest wall changed to stage IIIB The rate of up-stage in patients with stage 2/55 patients (3.6%) with reduction stage II before PET/CT was 37.5% and in stage - 16 patients with stage IIB before 18FDG PET/CT, after 18FDG PET/CT changed stage in 6/16 patients (37.5%), including patient from T2 to T1c and so from IIB to IIA stage, other patients (31.2%) increased the stage, including: III before PET/CT was 54.5% patients + patients changed to stage IV: patient with opposite side metastases and patient with multifocal bone metastases over other imaging methods in detecting + patients had invasive skin + chest wall, from T2 to T4 and so that they changed to stage IIIB metastases 18FDG PET/CT had low sensitivity + patient found carina lymph node, changed to stage IIIC cancer (T4d) or local advanced breast - patients with stage IIIB before FDG PET/CT, after 18 FDG PET/CT, there were 4/8 patients (50%) with stage changes: 18 302 from stage II and patients from stage III were found metastases and changed to stage IV, so that they had to change the primary treatment method (16.4%) 18 FDG PET/CT showed advantages lymph nodes like supraclavical nodes, inner mammary nodes, lung and bone with brain metastases In patients with high risk such as inflammatory type breast cancer, 18 FDG 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] Jourrnal of military pharmaco-medicine n09-2019 The role of 18FDG 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 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 18 FDG 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 patients and supraclavicular node in patient; patients had local recurrence lesions 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 - 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 posttreatment breast cancer patients Number of patients Rate (%) Lung 20 20.4 Bone 22 22.5 Liver 8.2 Soft tissue 8.2 Brain 1.0 Other 7.1 12 12.3 Location Distance metastases Recurrence 18 FDG 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 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 patients had both local recurrence and distance metastases 303 Jourrnal of military pharmaco-medicine n09-2019 Table 4: The recurrence or metastases detected on 18FDG PET/CT according to the indicative group Number of patients Patients with recurrent or metastases Rate (%) Evaluated post-treatment 53 19 35.8 Recurrence and metastases on CT, ultrasound, MRI 13 13 100 Recurrence, metastases on CT, ultrasound, MRI and increased CA15.3 12 11 Increased CA15.3 (> 25 U/mL) 20 11 55.0 98 54 55.1 Reason for indicating post-treatment 18 FDG PET/CT Total 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, 18 FDG PET/CT can detect metastases 304 91.7 with accuracy up to 87 - 90% while other imaging methods only have accuracy about 50 - 78% General guidelines recommend posttreatment 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 18 FDG 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: patients (3.6%) with lung metastases, patients (5.5%) with lung and bone metastases, patients (3.6%) with bone metastases and patients (3.6%) with contralateral side metastases Jourrnal of military pharmaco-medicine n09-2019 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%); 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 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 ACR ACR-SPR practice parameter for perfoming 18FDG PET/CT in oncology Resolution 2016, 25, pp.1-9 18FDG PET/CT EANM procedure guideline for tumour imaging: Version 2.0 Eur J Nucl Med Mol Imaging 2015, 42, pp.328-354 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 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 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 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 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.352-366 305 ... following objectives: To evaluate the role of 18FDG PET/CT in staging diagnosis in pre- treatment breast cancer patients and for finding recurrence lesions, metastases in post- treatment breast cancer. .. RESULTS AND DISCUSSION The role of 18FDG PET/CT in staging breast cancer Before 18FDG PET/CT scan, the almost of breast cancer patients were at T and T2 stage (85.5%) 14.5% of patients had a large breast. .. showed the role of 18FDG PET/CT with breast cancer stage IIB (T2N1/T3N0) [3, 4] Jourrnal of military pharmaco-medicine n09-2019 The role of 18FDG PET/CT in detecting recurrence and distance metastases