|Year : 2020 | Volume
| Issue : 4 | Page : 816-821
The prognostic significance of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography in early-stage nonsmall cell lung cancer
Caglayan Geredeli1, Mehmet Artac2, Ismail Kocak3, Lokman Koral4, Abdullah Sakin1, Tamer Altinok5, Bugra Kaya6, Mustafa Karaagac2
1 Department of Medical Oncology, Okmeydani Training and Research Hospital, Istanbul, Turkey
2 Department of Medical Oncology, Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey
3 Department of Nuclear Medicine, Konya Training and Research Hospital, Konya, Turkey
4 Department of Medical Oncology, Canakkale 18 March University, Faculty of Medicine, Canakkale, Turkey
5 Thoracic Surgery, Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey
6 Department of Nuclear Medicine, Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey
|Date of Submission||02-Nov-2017|
|Date of Decision||23-Jan-2018|
|Date of Acceptance||26-Feb-2018|
|Date of Web Publication||27-Apr-2018|
Department of Medical Oncology, Okmeydani Training and Research Hospital, Sisli, Istanbul
Source of Support: None, Conflict of Interest: None
Context: The prognostic criteria for early-stage nonsmall cell lung cancer (NSCLC) wait to be explored.
Aim: In this study, our aim was to evaluate the prognostic significance of the positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) value of the primary tumor in patients with a diagnosis of early-stage NSCLC who received surgical treatment.
Settings and Design: This was a multicenter retrospective design.
Materials and Methods: Patients who had been diagnosed with early-stage NSCLC and who underwent surgery for the condition were included in this study. The preoperative fluorodeoxyglucose (18F-FDG) PET/CT results of the patients were retrospectively accessed from their medical files. The disease-free survival (DFS) rates of patients who had SUVmax values above and below the determined cutoff value were compared.
Statistical Analysis Used: SPSS version 22 and Kaplan–Meier method were used for statistical analysis.
Results: A total of 92 patients were included in the study. The median age of the patients was 60 years (range: 36–79). The determined cutoff SUVmax value of the primary tumor was 13.6. A comparison of the DFS rates of the patients with an SUVmax value above and below 13.6 revealed a significant difference in patients with Stage I (22.9 months vs. 50.3 months; P = 0.02) and Stage II (28 months vs. 40.4 months; P = 0.04), Stage I + II (43.5 months vs. 26.1 months; P = 0,02), and Stage IIIA (14.7 months vs. 13.6 months; P = 0.92) NSCLC.
Conclusions: We found that in early-stage NSCLC patients, the SUVmax value of the primary mass in 18F FDG PET/CT was a prognostic indicator for the DFS rates.
Keywords: 18F-fluorodeoxyglucose positron emission tomography/computed tomography, early-stage nonsmall cell lung cancer, maximum standardized uptake value
|How to cite this article:|
Geredeli C, Artac M, Kocak I, Koral L, Sakin A, Altinok T, Kaya B, Karaagac M. The prognostic significance of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography in early-stage nonsmall cell lung cancer. J Can Res Ther 2020;16:816-21
|How to cite this URL:|
Geredeli C, Artac M, Kocak I, Koral L, Sakin A, Altinok T, Kaya B, Karaagac M. The prognostic significance of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography in early-stage nonsmall cell lung cancer. J Can Res Ther [serial online] 2020 [cited 2020 Sep 23];16:816-21. Available from: http://www.cancerjournal.net/text.asp?2020/16/4/816/231409
| > Introduction|| |
Lung cancer is a significant health problem in the world, and it is one of the leading causes of death due to cancer in the United States (US). Most lung cancer patients present to medical facilities at a locally advanced (Stage III) or a metastatic stage. The treatment options for lung cancer include surgery, radiotherapy, chemoradiotherapy, and chemotherapy. The 5-year survival rate is below 9% in these patients. The patients' survival time and response to therapy depend on multiple factors, which are affected by the cancer stage, the patients' general health status, and genetic influences. The 5-year survival rate for patients across all stages is approximately 14%.
There are differences even among patients at the same lung cancer stage with respect to their individual response to treatment, recurrence rate, and survival period. Therefore, clinicians must consider certain clinical and laboratory parameters to determine the best treatment strategy, prognosis, and follow-up plan in newly diagnosed patients. In recent years, the number of cases of nonsmall cell lung cancer (NSCLC) diagnosed during the early stage has increased as a consequence of the introduction of low-dose screening tomography. The primary treatment option in early-stage NSCLC is surgical intervention; however, 30%–70% of patients relapse after surgery., To prevent recurrence, an individual approach developed using the characteristics of the patient and his or her tumor is required for adjuvant therapy. Decisions regarding these individual therapies also depend on the known prognostic factors. In patients with Stage IB and IIA NSCLC who have undergone surgery, adjuvant treatment is also required due to prognostic high-risk conditions, such as a poorly differentiated tumor, lymphovascular invasion, wedge resection, a tumor size >4 cm, involvement of the visceral pleura, and a lack of lymph node sampling.,
Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has been proposed as a candidate these prognostic factors. Previous studies have used FDG-PET/CT to demonstrate that metabolic activity was correlated with the doubling time of the tumor and also the survival rate in early-stage NSCLC., However, conflicting published studies have reported that the maximum standardized uptake value (SUVmax) of the primary tumor is an independent prognostic factor.,,, The objective of this study was therefore to investigate the effect of the SUVmax of the primary tumor on the survival time in patients who underwent surgery for early-stage NSCLC and also received pretreatment with 18F-FDG PET/CT.
| > Materials and Methods|| |
This study had a multicenter and retrospective design. Patients who consecutively applied to the oncology departments of Meram Medical Faculty (Konya, Turkey), Dicle University Medical Faculty (Diyarbakır, Turkey), and Okmeydanı Training and Research Hospital (Istanbul, Turkey) were included in the study. Ethics committee approval was obtained from the Ethics Committee of the Necmettin Erbakan University Meram Medical Faculty. The study confirms the principles outlined in Helsinki Declaration (available at www.ub.edu).
This study included early-stage NSCLC patients who had been diagnosed via biopsy (Stage I, Stage II, and Stage IIIA) and undergone surgery. The staging was carried out using 18F-FDG PET/CT. The patients' characteristics, including their age, gender, general status, histological subtype, the presence of comorbidities, and smoking habits, were accessed in the patients' files that had been archived in the clinics. Patients who had not undergone surgery or staging with PET/CT were excluded from the study.
Positron emission tomography/computed tomography imaging
SUVmax values of the primary lung mass in the preoperative 18F-FDG PET/CT imaging were screened in the patient files. All institutions in this study used the same model for the FDG PET/CT imaging. Preoperative 18F-FDG PET/CT images were obtained using scanners (Siemens Biograph 6 LSO) in the nuclear medicine departments. After 6 h of fasting, the patients received an intravenous injection of 10–15 mCi 18F-FDG. One hour later, their entire body, from the top of skull to the thigh was scanned. The sections in the transaxial, coronal, and sagittal planes were investigated in different contrast windows. The SUVmax values were calculated for every FDG accumulation, which was considered to be abnormal. After the procedure, the images were evaluated and described by the nuclear medicine specialist.
Disease-free survival (DFS) was defined as the time between the operation date and the date of the relapse in relapsing patients and as the time between the operation date and the last application date to our clinic in those who did not experience a relapse. The data of the patients were recorded using the IBM Statistical Package for Social Sciences, version 22. For the statistical evaluation, a univariate analysis was carried out using the Kaplan–Meier method. Multivariate prognostic analyses of DFS were performed using the Cox proportional hazards regression model.
| > Results|| |
The study enrolled 92 patients who fulfilled the inclusion criteria. The median age of the patients is 60 years (range: 36–79); 83 were male, and 9 were female. Twenty-five patients were in Stage 1; 49 had been diagnosed with Stage II NSCLC, and 18 were found to be at Stage III [Table 1]. Sixteen of the patients were nonsmokers, and 76 currently smoked. Considering the histological subtypes of the tumors, 20 patients had adenocarcinoma (21.7%), 49 had squamous cell carcinoma (53.2%), and 23 were diagnosed with other subtypes (25%). The median follow-up period was 24.9 months. The average overall survival time could not be determined due to the short follow-up periods.
The median DFS was 34.8 months (95% confidence interval: 28.2–41.5). The median SUVmax value of the primary mass revealed by the 18F-FDG PET/CT images was 13.6. A comparison of the DFSs between the patients with SUVmax values both below and above 13.6 indicated that the DFS was 40.6 months in patients with a low SUVmax and 25.1 months in patients with a high SUVmax. The DFS was also significantly longer in patients with a lower SUVmax(P = 0.02). A comparison of the survival times by stage revealed that for Stage I, the DFS was 50.3 months in patients with a SUVmax value lower than 13.6 and 22.9 months in those with a SUVmax value above 13.6 (P = 0.02) [Table 2] and [Figure 1]. Regarding Stage II, the DFS was 40.4 months in patients with a SUVmax value lower than 13.6 and 28.0 months in those with SUVmax values above 13.6 (P = 0.048) [Table 2] and [Figure 2]. For Stage IIIA, the DFS was 14.7 months in NSCLC patients with a SUVmax value lower than 13.6 and 13.6 months in those with SUVmax values above 13.6 (P = 0.92).
|Table 2: Disease-free survival according to the values above and below a maximum standardized uptake value score of 13.6|
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|Figure 1: Disease-free survival in Stage I patients with an maximum standardized uptake value above and below 13.6|
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|Figure 2: Disease-free survival in Stage II patients with a maximum standardized uptake value above and below 13.6|
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The cutoff value for the SUVmax was 12.5 in nonsmokers. The DFS was 42.4 months in patients with an SUVmax value lower than 12.5 and 17.9 months in patients with an SUVmax value above 12.5 (P = 0.11). The cutoff value of the SUVmax was 13.9 in smokers. In addition, the DFS was 38.8 months in patients with an SUVmax value lower than 13.9 and 24.3 months in those with SUVmax values above 13.9 (P = 0.042) [Table 2].
Regarding the tumor subtypes, the cutoff value of the SUVmax in patients with adenocarcinoma was 11.3. The DFS was 46.2 months in patients with an SUVmax value lower than 11.3 and 19.7 months in those with SUVmax values >11.3 (P = 0.04) [Table 2] and [Figure 3]. The cutoff value of the SUVmax in patients with squamous cell carcinoma was 14.0. The DFS was 32.7 months in patients with an SUVmax value lower than 14.0 and 27.4 months in those with SUVmax values above 14.0 (P = 0.28) [Table 2]. When the entire nonsquamous cell carcinoma group was included, and the squamous cell carcinoma patients were excluded, the DFS was 44.8 months in patients with an SUVmax value lower than 13.6 and 20.5 months in patients with SUVmax values above 13.6 (P = 0.026) [Table 2].
|Figure 3: Disease-free survival in adenocarcinoma patients with a maximum standardized uptake value above and below 11.3|
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The SUV max value was statistically significant for DFS of Stage 1 and Stage 2 patients but was not statistically significant for DFS of Stage 3. So that Stage 1 and Stage 2 were evaluated together for multivariate analysis for DFS. Multivariant analysis was performed for sex, age, ECOG performance status, smoking status, comorbidity, histologic type of tumor and SUV max values. Only SUV max value was statistically significant in multivariate analysis (P = 0.003) [Table 3].
|Table 3: Multivariate analyses of disease-free survival in Stage I and II patients|
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| > Discussion|| |
In our study, the DFS scores were compared between early-stage NSCLC patients with SUVmax values below and above 13.6. At Stage I, DFS was 22.9 and 50.3 months for SUVmax values below and above 13.6, respectively (P = 0.02); in Stage II, The DFS was 28 and 40.4 months, respectively (P = 0.04). The differences were significant in stage I and stage II. In Stage IIIA, The DFS was 13.6 and 14.7 months, respectively (P = 0.92). The differences were not significant in Stage IIIA.
Several factors affect the survival of lung cancer patients, including the patient's age, general health status, stage of the tumor, and histological tumor type. In recent years, 18F-FDG PET/CT has frequently been used in lung cancer patients as well as in other cancer types. This modality is noninvasive and is typically employed for the diagnosis and staging of cancers and also to provide information about the prognosis of the tumor. Therefore, with respect to NSCLC, the investigator raised the question about the effect of the FDG uptake level on survival. However, previous studies that have focused on this topic have produced conflicting results. Hoang et al. conducted a retrospective study with advanced-stage NSCLC patients. In this study, the average SUVmax value of the primary tumor was 11.1, and there was no significant difference between the survival time of the patients with SUVmax values below and above 11.1. In another study, which focused on patients with advanced stage NSCLC, the effect of the SUVmax value on the prognosis was investigated. The median survival time was 10.5 months in the group with a SUVmax<12 and 8 months in the group with a SUVmax>12. The difference was not significant. However, in the study of van Elmpt W and Ulger et al., which was conducted with NSCLC patients who were in a locally advanced stage and were treated with definitive radiotherapy, the survival time was shorter in those with a high PET/CT SUVmax value than it was in patients with a low SUVmax value. These authors concluded that the PET/CT SUVmax value had a predictive value independently of the tumor size in the patients with locally advanced stage NSCLC., In our study, there was no significant difference between the DFS time in patients with an SUVmax value below and above 13.6 even when the Stage IIIA patients were included, which was similar to the results of the studies of Hoang et al. and Erdem et al.,
In one study conducted among early-stage NSCLC patients, Kim et al. compared Stage I and Stage II NSCLC patients who had FDG PET/CT SUVmax values below or above 6.7. They reported that the survival time was longer in the patients with a lower SUVmax value and concluded that a high SUVmax value might have prognostic value.
In another investigation carried out by Yıldırım et al. in NSCLC patients, an evaluation of the subgroups revealed that a high SUVmax value was correlated with poor survival in early-stage (Stages I and II) NSCLC patients. Chen et al. determined in their study that the survival time was longer in Stage I operated NSCLC patients with a low SUVmax value (below 4.7). In another study, Park et al. found that the 5-year survival rate was 82% in Stage I NSCLC patients with a high SUVmax value and 95.1% in those with a low SUVmax value. However, Kim et al. investigated the SUVmax values in Stage I and Stage II NSCLC patients; their comparison of the SUVmax values below and above 6.8 did not show any prognostic value. In another study, it was revealed that in the Stage I NSCLC patients, the FDG uptake level in the primary tumor was an independent prognostic factor regarding survival. In that particular study, the SUVmax cutoff value was 13.1, and the survival time in patients with a SUVmax value above 13.1 was significantly different than that of patients with SUVmax values below 13.1. Considering the meta-analysis carried out on this topic, Berghmans et al. evaluated the data of 1474 patients from 13 studies and used univariate analyses to demonstrate that SUVmax was a strong prognostic factor. A similar meta-analysis conducted by Paesmans et al. showed that the SUVmax value was a prognostic factor. In our present study, a comparison of the patients with SUVmax values below or above 13.6, which was determined as an SUVmax cutoff value of the primary tumor in NSCLC patients with Stage I and II, showed that the survival time was longer in patients with a lower SUVmax value than in patients with a higher SUVmax value; this conclusion was similar to those from the studies of Kim, Yıldırım, Chen, and Park and also to the meta-analyses of Berghmans and Paesmans.
Regarding the prognostic significance of the SUVmax value in the adenocarcinoma and squamous cell carcinoma groups, which are the histological subtypes of NSCLC, in a published study that focused on the subgroup analysis, the SUVmax cutoff values were 5.2 for the adenocarcinoma and 13.8 in the other histological subtypes of NSCLC. Our cutoff value for the adenocarcinoma subtype was 11.3. We analyzed the adenocarcinoma and squamous cell carcinoma subtypes with cutoff values below or above 11.3 and found that the survival time was significantly shorter in the adenocarcinoma subtype with SUVmax values above 11.3. The SUVmax cutoff was 14 for the squamous cell carcinoma subtype. In this subgroup, there was no significant difference between the patients with SUVmax values below or above 14.0.
This study had some limitations due to its retrospective design. After considering the previous studies in addition to ours, we found out that the cutoff values of the SUVmax of the primary mass in the PET/CT presented different results regarding early-stage NSCLC. The determined SUVmax cutoff values ranged between 5.7 and 13.8 in various studies. The reasons for these deviations might be regional and racial differences and also the different PET/CT devices used for the imaging. Nevertheless, a prospective, multicenter study with a large number of patients is needed to determine a standard SUVmax cutoff value. At the same time, the PET/CT SUVmax values of the primary mass in the operated NSCLC patients should be standardized; these values must be considered to identify patients who will require adjuvant therapy and also those who will be at high risk during the individualized adjuvant therapy. Similarly, as shown in previous studies and also in our study, in patients who display the histology of adenocarcinoma, which is a subtype of the operated NSCLC, a standardized SUVmax cutoff value should be determined in the adenocarcinoma subtype, as the SUVmax value of the PET/CT primary mass had prognostic value.
| > Conclusions|| |
This study indicated that the SUVmax value of the preoperative PET/CT primary mass had a prognostic value in NSCLC patients who had undergone surgery. As the SUVmax value guides the clinician in the decision of the treatment, it should be verified by large prospective studies; a standard cutoff value should also be determined.
Financial support and sponsorship
This study was funded by Selcuk University Research Support System, Konya, Turkey.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]