Study on PET/CT findings in patients with small cell lung cancer

To explore TNM stage and quantitative parameters (SUVmean, SUVmax, MTV, TLG) in small cell lung cancer patients who underwent 18F-FDG PET/CT before initial treatment. Subjects and methods: Retrospective analysis in 32 patients diagnosed with small cell lung cancer based on pathological results at the Oncology and Nuclear Medicine Department, Bachmai Hospital and 61 non-small cell lung cancer patients at 103 Military Hospital, from November 2009 to June 2019. They were underwent 18F-FDG PET/CT-scans before the treatment. The variables include: Location, tumor size, SUVmean, SUVmax, MTV and TLG of the tumor. Results: 32 small cell lung cancer patients (29 males, 3 females) and 61 non-small cell lung cancer patients (45 males, 16 females) with the mean age of 61.3 ± 9.5 and 64.3 ± 9.3, respectively. There was a significant difference of TNM stage between 2 groups. The ratio of expanded stage in non-small cell lung cancer was higher than that in small cell lung cancer (93.4% vs. 71.9%, p < 0.01). The SUVmean and SUVmax of primary tumor were higher in nonsmall cell lung cancer compared to small cell lung cancer.

Journal of military pharmaco-medicine no7-2019 STUDY ON PET/CT FINDINGS IN PATIENTS WITH SMALL CELL LUNG CANCER Bui Anh Thang1; Do Quyet2; Pham Ngoc Hoa2 SUMMARY Objectives: To explore TNM stage and quantitative parameters (SUVmean, SUVmax, MTV, 18 TLG) in small cell lung cancer patients who underwent F-FDG PET/CT before initial treatment Subjects and methods: Retrospective analysis in 32 patients diagnosed with small cell lung cancer based on pathological results at the Oncology and Nuclear Medicine Department, Bachmai Hospital and 61 non-small cell lung cancer patients at 103 Military Hospital, from 18 November 2009 to June 2019 They were underwent F-FDG PET/CT-scans before the treatment The variables include: Location, tumor size, SUVmean, SUVmax, MTV and TLG of the tumor Results: 32 small cell lung cancer patients (29 males, females) and 61 non-small cell lung cancer patients (45 males, 16 females) with the mean age of 61.3 ± 9.5 and 64.3 ± 9.3, respectively There was a significant difference of TNM stage between groups The ratio of expanded stage in non-small cell lung cancer was higher than that in small cell lung cancer (93.4% vs 71.9%, p < 0.01) The SUVmean and SUVmax of primary tumor were higher in nonsmall cell lung cancer compared to small cell lung cancer The MTV and TLG of mediastinal lymph nodes in small cell lung cancer were higher than those in non-small cell lung cancer Conclusion: PET/CT is a very good image technique in diagnosis and classification of staging of small cell lung cancer It distributes to distinguish between non-small cell lung cancer and small cell lung cancer based on the difference of SUVmean, SUVmax, MTV and TLG of the tumors * Keywords: Small cell lung cancer; PET/CT INTRODUCTION Lung cancer is one of the most common tumor types, representing 13% of newly diagnosed cancers worldwide Both the absolute and relative frequencies of lung cancer have risen dramatically Unfortunately, it remains by far the leading cause of cancer-related deaths, accounting for 18% of the total number of deaths [6] Small cell lung cancer (SCLC) accounting for 10% of clinical lung cancer cases, is an aggressive malignancy strongly associated with smoking It displays a distinct natural history characterized by a high growth fraction, rapid doubling time and early establishment of widespread metastatic lesions [3] In patients who present with SCLC, it is important to determine whether the cancer is limited or at an extensive stage Limited-stage cancer, which is potentially curable, is treated with chemotherapy and radiation, with surgical resection reserved for selected patients with stage I disease Extensive-stage cancer is incurable; systemic chemotherapy is used to improve quality of life and prolong survival [8] Pham Ngoc Thach Medical University Vietnam Military Medical University Corresponding author: Bui Anh Thang (thangcdha@gmail.com) Date received: 05/07/2019 Date accepted: 26/08/2019 119 Journal of military pharmaco-medicine no7-2019 18 F-fluorodeoxyglucose positron emission tomography-computed tomography 18 ( F-FDG PET/CT), which provides morphological and metabolic data of malignancy, has become an important non-invasive tool for the staging as well as for the assessment of the primary tumor and distant metastasis in lung cancer FDG uptake in the primary tumor measured as the maximum standardized uptake value (SUVmax) by PET, which well known measure indicating the disease activity or the aggressiveness of tumor, can be easily obtained and is the most widely used parameter for the analysis of 18 F-FDG PET images in clinical practice As we all known, metastasis occurs primary by dissemination not only through the lymphatic and blood vessels but local extension in SCLC In this study, we aim: To explore TNM stage and quantitative parameters (SUVmean, SUVmax, MTV, TLG) in SCLC patients who underwent 18F-FDG PET/CT before initial treatment SUBJECTS AND METHODS Clinical data We retrospectively analyzed the 18FFDG PET/CT findings of 32 newly diagnosed SCLC patients from November 2009 to June 2019, and 61 non-SCLC (NSCLC) patients as the control group All patients were defined by histological or cytological evidences The patients were referred to Nuclear Medicine and Oncology Center, Bachmai Hospital and 103 Military Hospital for initial staging with 120 PET/CT-scan before treatment Histological diagnosis of the tumors was based on the criteria of the World Health Organization (2015) [12] and TNM stage was determined according to the 8th lung cancer TNM classification of International Association for the Study of Lung Cancer FDG PET/CT imaging 18 F-FDG PET/CT-scans were performed with a wholebody PET/CT-scanner All patients had been fasting for at least hours before PET imaging, and serum glucose levels were measured to ensure that the results were 180 mg/dL All patients had a glucose level below 180 mg/dL and were injected intravenously with 0.15 0.20 mCi/kg (7 - 12mCi) FDG 45 60 minutes after the injection, data were acquired from the vertex to the upper thigh Immediately after CT, a PET-scan (PET/CT Biograph True Point, Siemens, Germany) was performed for about 25 minutes, with seven to eight bed positions and minutes/position PET images were reconstructed iteratively with CT data for attenuation correction, using an inline integrated Siemens Esoft Workstation system CT integrated positron emission tomography fusion images in transaxial, sagittal and coronal planes were evaluated visually, and SUVmax of lesions was obtained from transaxial images Imaging analysis The PET/CT images were reviewed by using the automatic PET/CT fusion software on the workstation A volumetric region- Journal of military pharmaco-medicine no7-2019 of-interest (ROI) around the outline of primary tumor in the SCLC was placed on the axial PET images using the semiautomatic software A threshold of 40% of the maximum signal intensity was selected to delineate ROI Then SUVmax, SUVmean, MTV and TLG were automatically calculated by the PET/CT fusion software and these values were recorded from the workstation Both radiologists who conducted the measurements together were blinded to the clinical details Figure 1: Measurement of SUV and MTV (Source: Nucl Med Mol Imaging, 2012 [14]) Statistical analysis Statistical analysis was done using SPSS 22.0 (Chicago, Illinois, USA) The mean of the measurement data was expressed as mean ± standard deviation (mean ± S.D) The differences of SUVmean, SUVmax, MTV and TLG of the tumor in independent groups were compared by using independent t-test P values less than 0.05 were considered signifcantly RESULTS Table 1: Chracteristics and TNM staging of SCLC and NSCLC patients Variables SCLC (n = 32) NSCLC (n = 61) p-value Age (mean ± SD) 61.3 ± 9.5 64.3 ± 9.3 0.144 Sex (n, %) Male Female 29 (90.6%) (9.4%) 45 (73.8%) 16 (26.2%) 0.055 Metastasis (n, %) 21 (65.6%) 37 (60.7%) 0.638 T stage (n, %) T1 - T2 T3 - T4 17 (53.1%) 15 (46.9%) 15 (24.6%) 46 (75.4%) 0.012 121 Journal of military pharmaco-medicine no7-2019 N stage (n, %) N0 - N1 N2 N3 (28.1%) 11 (34.4%) 12 (37.5%) (9.8%) 26 (42.6%) 29 (47.5%) 0.001 M stage (n, %) M0 M1a M1b M1c 24 (39.3%) (9.8%) 21 (34.4%) 10 (16.4%) 11 (34.4%) (15.6%) (25.0%) (25.0%) 0.545 Overall stage (n, %) I - II III IV (9,4%) (25%) 21 (65.6%) (3.3%) 22 (36.1%) 37 (60.6%) 0.022 Extensive stage (n, %) 23 (71.9%) 57 (93.4%) 0.009 32 SCLC patients (29 males, females) and 61 NSCLC patients (45 males, 16 females) with the mean age of 64.3 ± 9.3 and 61.3 ± 9.5, respectively There was not difference of age between two groups There were significant differences of TNM stage between two groups The ratio of extensive stage in SCLC was lower than that in NSCLC (71.9% vs 93.4%, p < 0.01) Table 2: Metastasis in SCLC compared to NSCLC on PET/CT Metastasis SCLC (n = 32) NSCLC (n = 61) p-value 11 (34.4%) (8.2%) 0.001 (3.1%) (9.8%) 0.415 Mediastinal lymph node 23 (71.9%) 61 (100%) 0.001 Neck lymph node 10 (31.3%) 21 (34.4%) 0.758 Oesophagus metastases (3.1%) (0%) 0.344 Hepatic metastases (9.4%) (9.8%) 0.943 Gastric metastases (3.1%) (0%) 0.344 Abdominal lymph node (12.5%) (8.2%) 0.489 Brain metastases (3.1%) (0%) 0.344 Bone metastases (21.9%) 21 (34.4%) 0.210 Pancreatic metastases (6.2%) (0%) 0.116 (0%) (1.6%) 1.00 Adrenal (3.1%) (18.4%) 0.156 Adrenal metastases (3.1%) (0%) 0.344 Soft-tissue metastases (6.2%) (0%) 0.116 27 (84.4%) 61 (100%) 0.004 Lung metastases Pleural metastases Renal metastases Metastases at least one location 122 Journal of military pharmaco-medicine no7-2019 All cases of NSCLC has metastasis at least one location (100%) compared to patients with SCLC (84.1%) (p < 0.01) The ratio of mediastinal lymph nodes metastasis was lower and the ratio of lung metastasis was higher in SCLC compared to those in NSCLC Table 3: SUVmean, SUVmax, MTV and TLG in SCLC and NSCLC PET/CT SCLC (n = 23) NSCLC (n = 61) p-value 52 55 0.642 SUVmean (median) 4.63 7.10 0.001 SUVmax (median) 8.57 16.40 0.001 MTV (median) 32.30 26.94 0.236 TLG (median) 256.62 194.72 0.605 34 21 0.001 SUVmean (median) 4.49 5.10 0.190 SUVmax (median) 7.84 10.20 0.139 MTV (median) 7.54 4.29 0.008 TLG (median) 30.77 22.94 0.050 Primary tumors Tumor size (median, mm) Mediastinal lymph nodes Tumor size (median, mm) The SUVmean and SUVmax of the primary tumors were lower in SCLC than those in NSCLC The tumor size, MTV and TLG of mediastinal lymph nodes were higher in SCLC compared to those in NSCLC Figure 2: Patient with primary tumor Figure 3: Lung metastasis 123 Journal of military pharmaco-medicine no7-2019 Figure 4: Mediastinal metastasis Figure 5: Brain metastasis Figure - were the PET-CT images of patients with SCLC at stage IV according to TNM classification DISCUSSION Although CT or magnetic resonance imaging provides precise anatomical and morphological information, the role of FDG-PET/CT has increased in diagnosis and classification of lung cancer staging [1] Recently, FDG uptake has been reported to be a prognostic factor in patients with lung cancer [1, Patz et al [10] demonstrated that patients with positive FDG-PET/CT results in treating lung cancer had a significantly worse prognosis than patients with negative results Therefore, we examined whether SUVmax correlates with tumor size, lymph node and distant metastases in patients with SCLC FDG PET/CT is an important adjunct examination in evaluating SCLC, combining functional informations (FDG PET) with 124 anatomical information (CT) FDG PET/CT is invaluable in clinical staging and restaging, guiding therapy, and suggesting prognosis SCLC is readily identified at FDG PET because of its high metabolic activity Some studies had reported improved staging accuracy with FDG PET compared with CT alone [2, 11] and FDG PET/CT was more accurate than FDG PET alone Use of FDG PET in combination with conventional imaging has led to upstaging from local stage-SCLC to extensive stage-SCLC in 19% of patients and to downstaging from extensive stage-SCLC to local stage-SCLC in 8% of patients Although FDG PET is inferior to CT or MRI for the detection of brain metastases, it is more sensitive and specific than conventional imaging for detecting metastatic disease Journal of military pharmaco-medicine no7-2019 18 F-FDG PET/CT has been increasingly used for staging, treatment response assessment and therapy planning in SCLC since it was introduced into clinical practice in 1998 Apart from qualitative assessment in the detection of metastases, PET/CT provides the opportunity of a semi-quantitative measure of tumor glycolysis using SUV SUVmax is the highest SUV measurement in the ROI and is the most commonly used measurement in clinical practice because of its being least affected by partial volume effects [5] SUVmax is also defined as a unique noninvasive method for studying biochemical and metastatic changes in cancer tissues The relationship between SUVmax of primary tumor and local extension, lymph node and distant organ metastasis was investigated Our results showed that the the SUVmean and SUVmax of the primary tumors were lower in SCLC than those in NSCLC The tumor size, MTV and TLG of mediastinal lymph nodes were higher in SCLC compared to those in NSCLC SUVmax has been correlated with tumor proliferation rate, tumor grade, and expression of glucose transporters, which are biomarkers in various types of malignant tumors Metastasis is the major cause of death due to several malignancies, including SCLC and it occurs primary by dissemination through the lymphatic and blood vessels Nambu et al (2009) had reported that the likelihood of lymph node metastasis increased with increase of SUVmax of the primary tumor in patients with NSCLC [9] Our results were consistent with their observations In their study, they also added when the SUVmax of the primary tumor was greater than 12, the probability of lymph node metastasis was high, reaching 70%, irrespective of the degree of FDG accumulation into the lymph node stations This finding would allow us to more sensitively predict the presence of lymph node metastases, including microscopic ones that cannot be detected by a direct evaluation of the lymph node stations In patients with NSCLC, Zhu et al [15] had shown that the average of SUVmax was significantly lower in patients without any metastasis than that with lymph node and/or distant organ metastasis These results further suggested that SUVmax may in partly reflect the potential of metastasis in primary tumor in NSCLC However, there was no upper threshold of SUVmax of NSCLC, above which lymph node and/or distant organ metastasis were always present Thus, even when a primary tumor in NSCLC shows high SUVmax exceeding 10 or 20, the presence of lymph node and/or distant organ metastasis is still inconclusive based on the evaluation of the SUVmax of the primary tumor The utility of PET in the initial staging of patients with SCLC has been evaluated in 12 studies comparing pre-treatment 18 F-FDG-PET to conventional staging procedures according to a meta-analysis [7] Study designs varied with regard to the extent of conventional staging, the use of PET alone or PET/CT, and the method used to define PET positivity In addition, some studies required biopsy of 125 Journal of military pharmaco-medicine no7-2019 all FDG-avid lesions that would alter stage, whereas others used clinical follow-up to confirm PET findings Unfortunately, several studies did not validate PET findings and stage alterations by either method SCLC is a highly metabolic malignancy, leading to a sensitivity of 100% for PET detection of primary tumors Overall, cumulative staging concordance was 84% between PET and conventional imaging with better concordance noted in the prospective (89%, range 83 - 100%) than the retrospective (80%, range 67 - 100%) studies [7] Of the 204 patients with local stage-SCLC by conventional imaging, 19% were up-staged to extensive by PET, with similar findings in the prospective (17%, range - 33%) and retrospective (20%, range - 54%) studies Of the 199 patients with extensive stage-SCLC by conventional imaging, 11% were downstaged to local stage by PET, with a much lower percentage of down-staged patients noted in the prospective (5%, range 11%) than retrospective (18%, range 40%) studies For most metastatic sites, PET was superior to standard imaging in both sensitivity and specificity However, PET was inferior to MRI or CT for the detection of brain metastases [7] CONCLUSION PET/CT is a very good image technique in diagnosis and staging of SCLC It distributes to distinguish between NSCLC and SCLC based on the difference of SUVmean, SUVmax, MTV and TLG of the tumors 126 REFERENCES Al-Sarraf N, Gately K, Lucey J et al Clinical implication and prognostic significance of standardised uptake value of primary nonsmall cell lung cancer on positronemission tomography: Analysis of 176 cases Eur J Cardiothorac Surg 2008, 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therapy, and suggesting prognosis SCLC is