The correlation between metabolic parameters in (18)F-FDG PET-CT and solid and micropapillary histological subtypes in lung adenocarcinoma

Objective: To investigate the prognostic values of the maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated from pretreatment (18)F-fluorodeoxy glucose ((18)F-FDG) PET-CT results of patients with advanced extranodal NK/T cell lymphoma (ENKTL). Methods: The clinic data, follow-up data and pretreatment (18)F-FDG PET-CT data of 45 patients with ENKTL of stage Ⅳ were collected. The optimal cutoff value of progression-free survival (PFS) of SUV(max), MTV and TLG were analyzed by using receiver-operating characteristic (ROC) curve. The Kaplan-Meier method, Log-rank test and COX proportional hazards model were used for survival analysis, univariate analysis and multivariate analysis, respectively. Results: The median SUV(max), MTV and TLG of 45 ENKTL patients were 17.98, 70.18 and 755.42, respectively. ROC curve showed that the area under the curve (AUC) of SUV(max), MTV and TLG were 0.504 (P=0.970), 0.868 (P<0.001) and 0.848 (P=0.001), respectively. The value of SUV(max) was too small to fit for calculating the cutoff value of AUC. The cutoff value of MTV was 42.54 (sensitivity =78.1% and specificity =84.6%), and the cutoff value of TLG was 435.15 (sensitivity=75.0% and specificity =76.9%). Univariate analysis showed that lactate dehydrogenase (LDH) level, epstein-barr virus (EBV)-DNA, Eastern Cooperative Oncology Group (ECOG) score, bone marrow, Korean prognostic index (KPI), MTV, TLG were significantly related with PFS (all P<0.05), and lactate dehydrogenase (LDH) level, EBV-DNA, ECOG score, primary tumor location, KPI, MTV, TLG were significantly related with overall survival (OS) (all P<0.05). Multivariate analysis showed that KPI, MTV and TLG were independent prognostic predictors of PFS and OS (all P<0.05). Conclusions: MTV and TLG of pretreatment (18)F-FDG PET-CT are independent prognostic factors for PFS and OS of patients with advanced ENKTL. MTV and TLG may be more fit for evaluating the prognosis of ENKTL patients than SUV(max).

Lung adenocarcinoma is histologically diverse but has distinct histologic growth patterns. There is no consensus on the clinical benefit of this histologic model. We aimed to evaluate the differences in the distribution of the preoperative primary tumor positron emission tomography (PET)/computed tomography (CT) standardized uptake values (SUVs) and survival in the lung adenocarcinoma subtypes. We retrospectively evaluated the data of 107 patients with resected lung adenocarcinoma who had preoperative PET/CT between 2005 and 2017 in a single center. Patients had lepidic, acinar, papillary, micropapillary, and solid histologic subtypes. We compared fluorodeoxyglucose SUVs and survival data of histologic subtypes. The median age of the patients was 62 years (40-75), 76.4% were male, the median SUVmax was 9.4 (1-36.7), and the median follow-up time was 29 months (3-135 months). The median overall survival (OS) was 71 months and the median progression-free survival (PFS) was 33 months. SUVmax was significantly different in histologic subtypes: values for papillary, micropapillary, solid, acinar, and lepidic subtypes were 9.7, 8, 12, 9.1, and 3.9, respectively (p = 0.000). Solid predominant adenocarcinoma had significantly higher SUVmax than the other subtypes (p = 0.001). Lepidic predominant adenocarcinoma had significantly lower SUVmax than the other subtypes (p = 0.000). There was no significant difference in OS between histologic subtypes (p = 0.66), but PFS was significantly different between the groups (p = 0.017), and the solid subtype had a shorter PFS than the other histologic subtypes. Lung adenocarcinoma consists of a diverse group of diseases. Different SUVmax values are seen in different histologic subtypes of nonmetastatic lung adenocarcinoma. Solid predominant types have high SUVmax values while lepidic predominant types have lower SUVmax values. The solid subtype had a shorter PFS than the other histologic subtypes.

Background The volume doubling time (VDT) is a key parameter in the differentiation of aggressive tumors from slow-growing tumors. How different histologic subtypes of primary lung adenocarcinomas vary in their VDT and the prognostic value of this measurement is unknown. Purpose To investigate differences in VDT between the predominant histologic subtypes of primary lung adenocarcinomas and to assess the correlation between VDT and prognosis. Materials and Methods This retrospective study included patients who underwent at least two serial CT examinations before undergoing operation between July 2010 and December 2018. Three-dimensional tumor segmentation was performed on two CT images and VDTs were calculated. VDTs were compared between predominant histologic subtypes and lesion types by using Kruskal-Wallis tests. Disease-free survival (DFS) was obtained in patients undergoing surgical procedures before July 2017. Univariable and multivariable Cox proportional hazards regression analyses were performed to determine predictors of DFS. Results Among 268 patients (mean age, 64 years ± 8 [standard deviation]; 143 men), there were 30 lepidic, 87 acinar, 109 papillary, and 42 solid or micropapillary predominant subtypes. The median VDT was 529 days (interquartile range, 278-872 days) for lung adenocarcinomas. VDTs differed across subtypes (P < .001) and were shortest in solid or micropapillary subtypes (229 days; interquartile range, 77-530 days). Solid lesions (VDT, 248 days) had shorter VDTs than subsolid lesions (part-solid lesions, 665 days; nonsolid lesions, 648 days) (P < .001). In the 148 patients (mean age, 64 years ± 8; 89 men) included in the survival analysis, 35 patients had disease recurrence and 17 patients died. VDT (<400 days) was an independent risk factor for poor DFS (hazard ratio, 2.6; P = .01) and higher TNM stage. Adding VDT to TNM stage improved model performance (C-index, 0.69 for TNM stage vs 0.77 for combined VDT class and TNM stage; P = .002). Conclusion Volume doubling times varied significantly according to the predominant histologic subtypes of lung adenocarcinoma and had additional prognostic value for disease-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ko in this issue.

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi-squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

Objective: To investigate the value of maximum Standardized Uptake Value(SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) calculated from (18)F-FDG PET-CT in predicting the presence of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. Methods: We retrospectively reviewed 137 lung adenocarcinoma patients with EGFR mutations testing and pretreatment (18)F-FDG PET-CT. Receiver Operating Characteristic (ROC) curve analysis was performed to quantify the predictive value of SUVmax、MTV、TLG. A multivariate logistic regression analysis was used to evaluate the predictive value of EGFR mutation. Results: Among 137 lung adenocarcinoma patients, 86(62.8%, 86/137) were identified with EGFR mutations. The SUVmax, MTV and TLG were 7.4, 5.28 cm(3,) 20.20, respectively. The optimal cut-off values of SUVmax, MTV and TLG were 7.99(AUC=0.658, 95% CI=0.566~0.752, P=0.002), 6.09 cm(3)(AUC=0.644, 95% CI=0.550~0.737, P=0.005), 35.08(AUC=0.650, 95% CI= 0.557~0.744, P=0.003), respectively. Multivariate analysis showed that TLG and smoking status were the most significant predictors of EGFR mutation(all P<0.05). Conclusion: TLG in (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung adenocarcinoma, and has certain reference value for predicting EGFR mutation.

Adenocarcinoma is the most common type of lung cancer, and pre-operative biopsy plays an important role to determine its major subtypes. As proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) in 2011, the predominant histological subtype of adenocarcinoma is an indicator of outcomes and recurrence rate. However, the value of CT-guided core biopsy in predicting the predominant subtype and detecting the presence of an aggressive subtype of adenocarcinoma, peripheral sub-solid nodule, has less been discussed. We retrospectively reviewed 318 consecutive peripheral sub-solid nodules that underwent percutaneous CT-guided lung biopsy and surgical resection, between October 2015 and December 2018 and were diagnosed as adenocarcinoma with histological subtype. The subtyping results from biopsy and surgical pathology were compared to evaluate the concordance rate. The overall concordance rate between biopsy and surgical pathology in determining the predominant histological subtype was 64%. Better concordance was found in small tumors (≤ 2cm), in predicting either predominant histology (χ2 = 7.091, P = 0.008) or high grade adenocarcinoma, micropapillary and/or solid subtype, MIP-SOL (χ2 = 22.301, P < 0.001). The analysis of ground glass opacity (GGO) component (C/T ratio) obtained significantly higher accuracy in the pure GGO group than in the other two groups in predicting predominant histology or high grade adenocarcinoma (χ2 = 17.560, P < 0.001 and χ2 = 61.938, P < 0.001, respectively). CT-guided core biopsies provide additional value in predicting the histological subtype of lung adenocarcinoma after surgical resection, especially in small tumors (≤ 2cm) or an initially pure GGO group.

To evaluate the prognostic role of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) measured by FDG-positron emission tomography (PET)/computed tomography (CT) in patients with primary lung adenocarcinoma undergoing surgical resection. All consecutive patients undergoing curative surgery for primary lung adenocarcinoma at the Thoracic Surgery Unit of the University Hospital of Parma between January 2009 and December 2014 were retrospectively analyzed. The cutoff point of each continuous PET parameter was determined through receiver operating characteristic curve and Youden index, using overall survival (OS) as the classification status. Univariate and multivariate Cox proportional hazards models were applied to evaluate the association between OS and potential prognostic variables, including SUVmax, MTV, and TLG. A total of 193 patients were considered eligible for this study. The mean 5-year OS rate was 70.5 ± 3.5%. Acinar and lepidic patterns were more frequently associated with absent or low (<2.5) SUVmax values [18F]FDG uptake. At univariate analysis, male sex, advanced stage, micropapillary and solid pattern, lymphatic, blood vessels and pleural invasion, high SUVmax, MTV, and TLG were significantly associated with poorer OS. Multivariate analyses revealed that only sex, stage, and TLG were independent factors for OS, with male sex, stage 3+4, and high TLG value (p = 0.041) significantly associated with poorer OS. In this study, [18F]FDG PET/CT parameters SUVmax, MTV, and TLG were prognostic factors in patients with surgically resected lung adenocarcinoma, able to predict OS and helping to further stratify these patients into prognostic subsets. Elevated TLG was also an independent predictor for shorter OS.

Objective: To analyze the clinical features and prognostic factors of different histological subtypes of lung adenocarcinoma. Methods: Data from 370 lung adenocarcinoma patients who underwent surgical resection for pathologically supported adenocarcinoma in our hospital between 2000 and 2003 were retro- spectively reviewed. The Kaplan-Meier method was used to estimate patient survival, and Cox’s proportional hazards model was performed for multivariate analysis. Results: The 5-year overall survival rate was 25.26%, and the mean survival time was 3.89 years. In multivariate analysis, histological subtype, incised margin residual, TNM stage, tumor size, and adjuvant chemotherapy were identified as independent survival predictors. The 5-year survival rate in bronchioloalveolar adenocarcinoma (BAC) patients was 41.30%, higher than in patients with other subtypes of lung adenocarcinoma (P=0.002). No significant difference was found in the prognosis among patients with different subtypes of adenocarcinoma without a BAC component. Conclusion: Ade-nocarcinoma with a BAC component is an independent subtype of lung adenocarcinoma. Its prognosis lies between those of BAC and adenocarcinoma without BAC. Histological subtype, incised margin residual, TNM stage, tumor size, and adjuvant chemotherapy are independent survival predictors.

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various human cancers. This study examined the prognostic value of these metabolic tumor parameters measured by pretreatment (18)F-FDG PET/CT in patients with salivary gland carcinomas. Forty-nine patients with intermediate- or high-grade salivary gland carcinomas who underwent definitive surgery with or without radiotherapy or chemoradiotherapy were evaluated preoperatively by (18)F-FDG PET/CT. Maximum standardized uptake values (SUV max), MTV, and TLG were measured for each patient. Univariate and multivariate analyses were used to identify clinicopathologic and imaging variables associated with progression-free survival (PFS) and overall survival (OS). Univariate analyses included the following variables: age, sex, pT and pN classifications, overall pTNM stage, histologic grade, resection margin, tumor lymphovascular invasion and perineural invasion, postoperative adjuvant therapy, gross total volume, SUV max, MTV, and TLG. The 3-y PFS and OS rates for all study patients were 66.9% and 81.6%, respectively. The median SUV max, MTV, and TLG were 5.1 (range, 1.7-21.5), 16.2 mL (1.0-115.1 mL), and 24.4 g (2.1-224.4 g), respectively. Univariate analyses showed that there were significant correlations between pT classification, pN classification, MTV, and TLG and both PFS and OS (P < 0.05). However, SUV max was not associated with either PFS (P = 0.111) or OS (P = 0.316). Multivariate analyses revealed that MTV (P = 0.011; hazard ratio, 11.50; 95% confidence interval, 1.45-91.01) and TLG (P = 0.038; hazard ratio, 3.55; 95% confidence interval, 1.07-11.76) were independent variables for PFS. Pretreatment values of MTV and TLG are independent prognostic factors in patients with intermediate or high-grade salivary gland carcinomas.

Prognostic Value of the Quantitative Metabolic Volumetric Measurement on 18F-FDG PET/CT in Stage IV Nonsurgical Small-cell Lung Cancer

Early-Stage Lung Adenocarcinoma Treated With Stereotactic Body Radiation Therapy: Prognostic Factors for Treatment Outcomes

ObjectiveOur prospective study aims to define the correlation of EGFR(epidermal growth factor receptor) mutations with major histological subtypes of lung adenocarcinoma from resected and non-resected specimens, according to the WHO 2015 classification, in Moroccan North East Population.MethodsEpidermal growth factor receptor mutations of 150 primary lung adenocarcinoma were performed using Real-Time PCR or SANGER sequencing. SPSS 21 was used to assess the relationship between histological subtypes of lung adenocarcinoma and EGFR mutation status.Results25 mutations were detected in the series of 150 lung adenocarcinomas, most of which were found in cases with papillary, acinar, patterns than without these patterns and more frequently occurred in the cases without solid pattern than with this pattern. A significant correlation was observed between EGFR mutation and acinar (P = 0,024), papillary pattern (P = 0,003) and, negative association with a solid pattern (P < 0,001). In females, EGFR mutations were significantly correlated with the acinar pattern (P = 0,02), whereas in males with the papillary pattern (P = 0,01). Association between the histologic component and exon 19 deletions and exon 21 mutations were also evaluated and, we found a significant correlation between the papillary major pattern with exon 19 mutations (P = 0,004) and, ex21 with the acinar component (P = 0,03).ConclusionAn analysis of resected and non-resected lung ADC specimens in 150 Moroccan Northeast patients, revealed that acinar and papillary patterns may predict the presence of a mutation in the EGFR gene. While the solid major pattern may indicate a low mutation rate of the EGFR gene.

BackgroundAccording to the International Multidisciplinary Classification of Lung Adenocarcinoma (LAD) by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) in 2011, the diagnosis of LAD is changing from simple morphology into a comprehensive multidisciplinary classification. The aim of this study is to detect the expression of Notch-1 and analyze its clinicopathological or prognostic significance in different histological subtypes of Lung Adenocarcinomas (LADs).MethodsWestern blot and Semi-quantitative Reverse transcription-polymerase chain reaction (RT-PCR) assays, as well as immunohisitochemistry, were performed to detect the expression of Notch-1 in LAD cells and tissue samples. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the correlation of Notch-1 expression with clinicopathological factors and prognosis of LAD patients.ResultsThe expression level of Notch-1 protein in LAD cell lines or tissues was significantly lower than that in normal human bronchial epithelial cell line (16HBE) or nontumor tissues (P < 0.05). By statistical analyses, it was observed that negative Notch-1 expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.026) in LAD patients. Also, the recurrence rate of Notch-1-positive group was higher than the Notch-1-negative group (P = 0.001), and patients with positive Notch-1 expression have a prolonged progression of overall survival (P = 0.033). More interestingly, the expression of Notch-1 protein was often observed to be negative in solid predominant adenocarcinoma (SPA) tissues, but highly expressed in papillary predominant adenocarcinoma (PPA) and micropapillary predominant adenocarcinoma (MPA) tissues. Kaplan-Meier survival analysis showed that patients with positive Notch-1 expression had a prolonged progression of overall survival compared with those with negative Notch-1 expression (P = 0.033). The median survival time of Notch-1-positive or negative patients was 64.6 months (95% CI: 31.497-97.703 months) or 36.0 months (95% CI: 12.132-59.868 months).ConclusionsNotch-1 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in LAD for diagnosis or prognosis.

Analysis of PET-CT Derived Radiomic Biomarkers with Efficacy, Safety, and Expansion of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL)

The histologic heterogeneity of lung adenocarcinoma is well known. Many histologic subtypes have been described, and recently their prognostic and predictive value has emerged. Laser capture microdissection may aid in the isolation of cancer cells from distinct subtypes of lung adenocarcinoma, thus enabling the description of their specific molecular features. Characterization of epidermal growth factor receptor (EGFR) mutations in histologic subtypes of lung adenocarcinoma has become an important issue. The purpose of this study was to analyze EGFR mutations in exons 18-21 in single histologic subtypes of lung adenocarcinoma after laser capture microdissection. A revision and reclassification of a series of 208 non-small cell lung cancers was conducted, and 62 adenocarcinomas with a total of 119 histologic component subtypes were identified. Laser capture microdissection of each subtype was performed. EGFR mutations in exons 18-21 were detected using polymerase chain reaction single-strand conformation polymorphism and direct DNA sequencing. EGFR mutations were detected only in 3 out of the 62 adenocarcinomas analyzed. Two adenocarcinomas harbored EGFR mutations in exon 19 (the E746-T751 deletion VA insertion and the LREAT deletion) and one adenocarcinoma the EGFR exon 21 L858R missense point mutation. EGFR mutations were observed in all component subtypes. This suggests that, in a patient with lung adenocarcinoma, EGFR mutations are not associated with particular component histologic subtypes and probably occur at an early stage of tumorigenesis. Notably, 2 out of the 3 mutated adenocarcinomas had a bronchioloalveolar component, whereas the third mutated adenocarcinoma had a papillary subtype. Although we detected EGFR mutations only in 3 out of 62 adenocarcinomas and EGFR mutations were present in every subtype of each mutated adenocarcinoma, our research might represent a basis for further studies in characterizing molecular profiles of different component subtypes of lung adenocarcinoma.