The value of 18FDG PET/CT for initial staging diagnosis of breast cancer – Nguyen Trong Son

Journal of military pharmaco-medicine n 0 6-2018 171 THE VALUE OF 18FDG PET/CT FOR INITIAL STAGING DIAGNOSIS OF BREAST CANCER Nguyen Trong Son*; Nguyen Danh Thanh** SUMMARY Objectives: To determine the value of 18FDG PET/CT in initial staging diagnosis of breast cancer patients. Subjects and methods: 36 breast cancer patients were performed 18FDG PET/CT for initial staging diagnosis before the treatment. Results: The 18FDG PET/CT changed in 6/36 patients (16.7%) by T stage, in 11/36 patients (30.6%) by N stage, detected metastasis in 8 patients. After 18FDG PET/CT, 13/36 patients (36.1%) upstaged diagnosis which included 8/24 patients (33.3%) at stage II and 5/8 patients (62.5%) at stage III. The 18FDG PET/CT did not change diagnosis in patients with clinical stage I. Conclusion: 18FDG PET/CT scan could effectively detect axillary and extra-axillary nodes, distant metastasis with great value in staging diagnosis in breast cancer patients. * Keywords: Breast cancer; 18FDG-PET/CT; Staging diagnosis. INTRODUCTION Breast cancer is diagnosed based on clinical symptoms, histology and diagnostic imaging. Common diagnostic imaging tools included mammography, ultrasound, computed tomography scan (CT-scan) and lately magnetic resonance imaging (MRI). Early diagnosis of breast cancer in examination periods and screening programs has brought great value in successful treatment. Positron emission tomography/computed tomography with flourine-18- fluorodeoxyglucose (18FDG PET/CT) allowed early detection of pathological metabolism before changing anatomy and physiology, providing important information for accurate staging and thence, proposing appropriate treatment regimen. The value of 18FDG PET/CT had been demonstrated in accurate diagnosis of tumor location, staging progress of breast cancer, evaluating axillary and extra-axillary lymphatic nodes (upper and lower clavicular nodes, internal mammary nodes). 18FDG PET/CT also works as a significant tool in evaluating abdominal, thoracic and bone metastasis at the same time. A recent research revealed that post 18FDG PET/CT changed staging in 1/3 and changed first choice treatment in 1/6 of breast cancer patients [5]. * Vietduc Hospital ** 103 Military Hospital Corresponding author: Nguyen Trong Son ([email protected]) Date received: 17/05/2018 Date accepted: 21/06/2018 Journal of military pharmaco-medicine n 0 6-2018 172 In Vietnam there were about 10 nuclear facilities over country applying PET/CT. This contributed to improve the quality of diagnosis and treatment for cancer patients. A few studies were conducted by using 18FDG PET/CT in patients with breast cancer. However, this is not yet a systematic, fully documented about diagnostic value for 18FDG PET/CT. The indication of PET/CT for which stage of disease will be better... Therefore, the study was carried out with the objectives: To determine the value of 18FDG PET/CT for staging diagnosis in breast cancer patients. SUBJECTS AND METHODS 1. Subjects. 36 patients diagnosed with breast cancer by histology underwent 18FDG PET/CT scan from 2013 to 2017 in Vietduc Hospital and Bachmai Hospital for staging diagnosis before treatment. Before 18FDG PET/CT, patients' staging according to TNM classification of AJCC- 2010 (American Joint Committee on Cancer) was based on clinical examinations, CT-scan and MRI. 2. Methods. Patients underwent whole body 18FDG PET/CT scan. Siemens PET/CT Biograph6 system was used. 18FDG dose is 0.15 mCi/kg. The results were analyzed by both nuclear medicine doctor and radiologist with CT-scan images, PET images and overlay images combined with clinical history and pre-scan CT and MRI images: identified lesions with increased focus of 18FDG on PET/CT. The staging of patients was compared between pre-and post-18FDG PET/CT scan. RESULTS Before 18FDG PET/CT scan, patients' staging was based on clinical examinations, mammography and breast ultrasound. Most of the patients (83.1%) were diagnosed with T1, T2 stage with tumor size < 5 cm, without infiltration of thoracic wall and skin, no clear clinical symptoms. Patients with thoracic wall and skin infiltration was 16.7%. About 58.3% of patients was diagnosed without axillary lymphatic nodes. According to TNM classification, before 18FDG PET/CT scan, 11.1% of patients were in stage I; 66.7% in stage II; 22.3% in stage III; 0% in stage IV. Using 18FDG PET/CT, we could determine original tumor in all 36/36 patients (100%), tumor size range from 1.1 - 7.6 cm, 88.9% < 5 cm, medial 3.04 ± 1.52 cm. 22/36 patients (61.1%) showed axillary lymphatic nodes (armpit and internal mammary nodes), with 43 nodes, size range from 0.4 - 3.1 cm; medial 1.11 ± 0.54 cm (37.2% < 1 cm; 53.5% 1 - 2 cm; 9.3% > 2 cm). Distant metastasis was determined in 8 patients (22.2%), including thoracic, bone, opposite breast and axillary breast. The 18FDG PET/CT scan changed results in evaluating tumor infiltration (T), nodes (N) and distant metastasis (M) compared with pre-scan results, thus changed the overall patients' staging. Journal of military pharmaco-medicine n 0 6-2018 173 Table 1: Change in evaluating tumor infiltration (T) after 18FDG PET/CT-scan. Before 18FDG PET/CT scan After 18FDG PET/CT scan T Patients T1 T2 T3 T4 T1 5 5 - - T2 25 3 19 - 3 T3 0 - - - - T4 6 - - - 6 Total 36 8 19 - 9 Post-18FDG PET/CT-scan changed the tumor infiltration stage in 6 patients: 3 patients changed from T2 to T1 due to tumor size; 3 patients from T2 to T4 due to thoracic wall or skin infiltration. Table 2: Changes in evaluating nodes (N) after 18FDG PET/CT-scan. Before18FDG PET/CT After18FDG PET/CT N Patients N0 N1 N2 N3 N0 21 13 6 1 1 N1 11 1 9 - 1 N2 2 - 1 1 N3 2 - - - 2 Total 36 14 15 2 5 After 18FDG PET/CT scan, results of nodes stage diagnosis changed in 11/36 patients (30.6%): 6 patients changed from N0 to N1; 1 patient changed from N0 to N2; 1 patient changed from N0 to N3; 1 patient changed from N1 to N3 (detected another axillary lymphatic node in opposite armpit); 1 patient changed from N2 to N3 (detected 4 axillary lymphatic nodes, 2 in right armpit and 2 in left armpit, and mediastinum nodes); 1 patient changed from N1 to N0. After 18FDG PET/CT scan, 8 patients were diagnosed with distant metastasis: 1 with thoracic metastasis; 2 with bone metastasis; 2 with bone and thoracic metastasis; 1 with opposite breast metastasis; 1 with axillary breast, and 1 with both thoracic, opposite breast and axillary breast metastasis. Journal of military pharmaco-medicine n 0 6-2018 174 Table 3: Changes in evaluating breast cancer stage after 18FDG PET/CT-scan. Stage before PET/CT Stage after18FDG PET/CT Stage No. of patients I IIa IIb IIIa IIIb IIIc IV I 4 4 - - - - - - IIa 14 1 8 3 - - - 2 IIb 10 - 1 6 - 1 2 IIIa 0 0 IIIb 6 - - - - 3 1 2 IIIc 2 - - - - - - 2 IV 0 0 Total 36 5 9 9 4 1 8 After 18FDG PET/CT scan, 13/36 patients had been diagnosed with increased stage compared with pre-scan diagnosis. 5/14 patients who had pre-scan diagnosis as stage IIa increased stage post-scan: 1 patient had axillary breast (SUVmax = 3.69), 1 patient had thoracic metastasis who were classified as stage IV; 3 patients had nodes and were classified as stage IIb. 3/10 patients with pre-scan diagnosis as stage IIb increased stage post-scan: 1 patient had opposite breast metastasis (SUVmax = 6.46) and 1 patient had multiple bone metastasis and were classified as stage IV; 1 patient had thoracic wall and skin infiltration, changed from T2 to T4c, classified as stage IIIb. 3/6 patients with pre-scan diagnosis as stage IIIb increased stage post-scan: 1 had thoracic metastasis (SUVmax = 3.1), 1 patient had thoracic and bone metastasis (SUVmax = 2.85 and 3.1) and were classified as stage IV; 1 was newly detected lower clavicular nodes (SUVmax = 5.88), changed from N2 to N3, thus changed from stage IIIb to IIIc. 2 patients with pre-scan classified as stage IIIc increased stage to stage IV: 1 patient had axillary breast, thoracic and bone metastasis; 1 patient had multiple bone metastasis. 2/36 patients decreased stage result after 18FDG PET/CT: 1 patient had tumor size < 2 cm, changed from T2 to T1c, therefore change from stage IIa to stage I. 1 patient changed from T2 to T1c due to different tumor size detected between pre- and post-scan and changed from stage IIb to stage IIa. There were 4 patients changed from stage II to stage IV and 4 patients changed from stage III to stage IV and also changed treatment regimen (22.2%). Journal of military pharmaco-medicine n 0 6-2018 175 DISCUSSION 18FDG PET/CT scan had great value in diagnosing TNM stage and also helps to categorize cancer stage. The diagnosis is of great importance to choose appropriate treatment for patients. Some study showed unclear role of 18FDG PET/CT scan in patients who had early stage breast cancer (tumor size < 2 cm and no clear palpated nodes). The sensitivity of 18FDG PET/CT scan in detecting axillary nodes was lower than sentinel node injection technique. However, in the patients who had inflammatory breast cancer or local progressing breast cancer, 18FDG PET/CT scan effectively detected distant metastasis, especially in breast cancer stage IIb (T2N1/T3N0) [2]. In this study, we had 4 patients with stage I cancer who had no change in classification after 18FDG PET/CT scan. This result was similar to the remarks that only patient with cancer stage II or III will benefit from 18FDG PET/CT scan. Garami Z, Hascsi Z [1] conducted a study on 115 breast cancer patients who had tumor size < 4 cm and had no detection of distant metastasis and local lymphatic nodes using other imaging technique. The sensitivity in detecting original tumor of 18FDG PET/CT scan was 93%. Nodes ultrasound scan had sensitivity of 30% and specificity of 95% while 18FDG PET/CT scan was 72% and 96%, respectively. 18FDG PET/CT scan also detected distant metastasis in 8 patients. The result of 18FDG PET/CT scan changed patients' stage in 54 patients (47%) and changed treatment regimen in 18 patients (15.6%). Furthermore, 18FDG PET/CT scan could detect distant metastasis in 7 - 8% patients when other imaging technique failed. Between progressing cancer and early stage cancer (tumor size 2 - 3 cm; N0) was the intermediate grade (N1, stage IIa, IIb and T3N1 or IIIa). Most authors agreed that 18FDG PET/CT scan had great value in the intermediate grade. It detected extra-axillary lymphatic nodes and hidden distant metastasis. Groheux et al [2] performed 18FDG PET/CT scan with 254 patients who had breast cancer over 2 cm and stage from IIa to IIIc (based on clinical examinations, mammography, MRI and ultrasound). The study showed 18FDG PET/CT scan modified cancer stage in 77 patients (30.3%), detected new lymphatic nodes in 40 patients (upper and lower clavicular nodes, internal mammary nodes) and distant metastasis in 53 patients. Suleman [5] investigated the role of 18FDG PET/CT scan in staging breast cancer. His study showed 18FDG PET/CT scan had limited sensitivity in small tumor: PET/CT sensitivity < 48% in T1 grade (< 2 cm), < 9% when tumor size < 1 cm (T1a and T1b). PET/CT scan had limited value in stage I breast cancer (N0 and tumor size < 2 cm). These patients often underwent operation and sentinel nodes biopsy. Riedl C.C, Slobod E et al (2014) [4] performed PET/CT scan in 134 breast cancer patients with stage from I to IIIc (clinical examination). The results changed patients' stage to stage IV from I and IIa in 5% of patients, from stage IIb in 17% of patients, from IIIa in 31% of patients and 50% of patients from stage IIIb and IIIc. Journal of military pharmaco-medicine n 0 6-2018 176 Krammer (2015) [3] performed PET/CT scan in 101 patients who had T2 grade or over or had positive nodes. PET/CT modified nodes grade or detected metastasis in 19% of the patients, changed first choice treatment method in 11% of the patients. CONCLUSION In 36 breast cancer patients, 18FDG PET/CT scan results modified cancer grade according to T grade in 6/36 patients (16.7%), according to N grade in 11/36 patients (30.6%) and detected distant metastasis in 8 patients. Cancer stage progressed in 13/36 patients (36.1%) including 8/24 patients (33.3%) in stage II and 5/8 patients (62.5%) in stage III. 18FDG PET/CT scan didn't restage breast cancer patients with stage I. REFERENCES 1. Garami Z, Hascsi Z, Varga J. The value of 18FDG PET/CT in early stage breast cancer compared to traditional diagnostic modalities with an emphasis on changes in disease stage designation and treatment plan. The Journal of Cancer Surgery, EJSO. 2012, 38, pp.31-37. 2. Groheux D, Alecxandre Cochet A, Olivier Humbert. 18F-FDG PET/CT for staging and restaging of breast cancer. J Nucl Med. 2016, 57, pp.17-26. 3. Krammer J, Schnitzer A, Kaiser C.G. FDG PET/CT for initial staging in breast cancer patients is there a relevant impact on treatment planning compared to conventional staging modalities?. Eu Radiol. 2015, 25, pp.2460-2469. 4. Riedl C.C, Slobod E et al. Retrospective analysis of FDG PET/CT for staging asymptomatic breast cancer patients younger than 40 years. J Nucl Med. 2014, 55, pp.1578-1583. 5. Suleman Surti. Radionuclide methods and instrumentation for breast cancer detection and diagnosis. Semin Nucl Med. 2013, 43, pp.271-280.