18F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study.

PURPOSE: To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease. METHODS: A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT. RESULTS: In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional diagnostic information for 77.4% of patients, and 89.6% of patients benefited from PET/CT examination. CONCLUSIONS: FDG PET/CT is a valuable tool for clinical diagnosis of FUO/IUO, and it is of great significance in further investigating the usefulness of PET/CT in non-neoplastic diseases.

Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: A subset of patients with non-small cell lung cancer (NSCLC) fosters mixed responses (MRs) to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) or chemotherapy. However, little is known about the clinical and molecular features or the prognostic significance and potential mechanisms. METHODS: The records of 246 consecutive patients with NSCLC receiving single-line chemotherapy or TKI treatment and who were assessed by baseline and interim positron emission tomography/computed tomography scans were collected retrospectively. The clinicopathological correlations of the MR were analyzed, and a multivariate analysis was performed to explore the prognostic significance of MR. RESULTS: The overall incidence of MR to systemic therapy was 21.5% (53/246) and predominated in patients with stage IIIB-IV, EGFR mutations and those who received TKI therapy (p < .05). Subgroup analyses based on MR classification (efficacious versus inefficacious) showed significant differences in subsequent treatment between the two groups (p < .001) and preferable progression-free survival (PFS) and overall survival (OS) in the efficacious MR group. Multivariate analyses demonstrated that the presence of MR was an independent unfavorable prognostic factor for PFS (hazard ratio [HR], 1.474; 95% confidence interval [CI], 1.018-2.134; p = .040) and OS (HR, 1.849; 95% CI, 1.190-2.871; p = .006) in patients with NSCLC. Induced by former systemic therapy, there were more T790M (18%), concomitant EGFR mutations (15%), and changes to EGFR wild type (19%) in the MR group among patients with EGFR mutations, which indicated higher incidence of genetic heterogeneity. CONCLUSION: MR was not a rare event in patients with NSCLC and tended to occur in those with advanced lung adenocarcinoma treated with a TKI. MR may result from genetic heterogeneity and is an unfavorable prognostic factor for survival. Further studies are imperative to explore subsequent treatment strategies. The Oncologist 2017;22:61-69Implications for Practice: Tumor heterogeneity tends to produce mixed responses (MR) to systemic therapy, including TKI and chemotherapy; however, the clinical significance and potential mechanisms are not fully understood, and the subsequent treatment after MR is also a clinical concern. The present study systemically assessed patients by PET/CT and differentiated MR and therapies. The study identified a relatively high incidence of MR in patients with advanced NSCLC, particularly those treated with targeted therapies. An MR may be an unfavorable prognostic factor and originate from genetic heterogeneity. Further studies are imperative to explore subsequent treatment strategies.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Dynamic 18 F-FDG PET/CT can predict the major pathological response to neoadjuvant immunotherapy in non-small cell lung cancer.

Major pathological response (MPR) is a potential surrogate for overall survival. We determined whether the dynamic changes in 18 F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) were associated with MPR in patients receiving neoadjuvant immunotherapy. Forty-four patients with stage II-III non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy and radical surgery were enrolled. Moreover, 18 F-FDG PET/CT scans were performed at baseline and within 1 week before surgery to evaluate the disease. All histological sections were reviewed to assess MPR. The detailed clinical features of the patients were analyzed. The reliability of the clinical variables was assessed in differentiating between MPR and non-MPR using logistic regression. Receiver-operating characteristic (ROC) curve analysis identified the SUVmax changes threshold most associated with MPR. Most of the patients were pathologically diagnosed with squamous cell carcinoma and received anti-PD-1 antibodies plus chemotherapy. The immunotherapy regimens included nivolumab, pembrolizumab, and camrelizumab. MPR was observed in more than half of lesions. Tumors with MPR had a higher decrease in the longest dimension on dynamic PET/CT than those without MPR. Furthermore, the decline in SUVmax was significantly different between MPR and non-MPR diseases, and MPR lesions had a prominent mean reduction in SUVmax. SUVmax reduction was independently associated with MPR in the multivariate regression. On ROC analysis, the threshold of SUVmax decrease in 60% was associated with MPR. Dynamic changes in SUVmax were associated with MPR. The tumors with MPR showed a greater PET/CT response than those without MPR. A SUVmax decrease of more than 60% is more likely to result in an MPR after receiving neoadjuvant immunotherapy.

[Clinical value of PET in identifying cervical nodal metastases of tongue cancer: a comparison with CT/MRI and clinical palpation in 38 cases].

OBJECTIVE: To assess the value of PET in the identification of cervical nodal metastases of tongue cancer in comparison with CT/MRI and clinical palpation. METHODS: Thirty-eight patients with tongue cancer underwent PET and CT/MRI within 2 weeks before surgery. The results of PET, CT/MRI, and clinical palpation were interpreted separately to assess the regional lymph node status, using histopathological analysis as the golden standard. The differences in the sensitivity, specificity and accuracy among the imaging modalities and clinical palpation were analyzed. RESULTS: The sensitivity of PET for nodal metastasis identification was 11.1% higher than that of CT/MRI (83.3% vs 72.2%, P=0.423) and 16.6% higher than that of clinical palpation (83.3% vs 66.7%, P=0.248). The specificity of PET was 5% higher than that of CT/MRI (80% vs 75%, P=0.703) and 15% higher than that of clinical palpation (80% vs 65%, P=0.288). The accuracy of PET, CT/MRI, and clinical palpation in identifying cervical nodal metastases was 81.6%, 73.7% and 65.8%, respectively. CONCLUSION: The sensitivity, specificity and accuracy of PET for detecting cervical nodal metastases are greater than those of CT/MRI and clinical palpation. Although the results failed to show statistically significant differences, we still recommend that PET be used as a supplementary modality for identifying nodal metastases of tongue cancer.

[Clinical application of positron-emission tomography for the identification of cervical nodal metastases of head and neck cancer compared with CT or MRI and clinical palpation].

OBJECTIVE: To evaluate the value of positron-emission tomography (PET) for the identification of cervical nodal metastases of head and neck cancer compared with CT/MRI and clinical palpation. METHODS: Forty patients of head and neck cancer underwent PET and CT/MRI examination 2 weeks before surgery. PET, CT/MRI and clinical palpation were interpreted separately to assess regional lymph node status. Histopathologic analysis was used as the gold standard for assessment of the lymph node involvement. Differences in sensitivity, specificity and accuracy among the imaging modalities and clinical palpation were analyzed. RESULTS: The sensitivity of PET for the identification of nodal metastases was 14.3% higher than that of CT/MRI (P = 0.648) and 14.3% higher than that of clinical palpation (P = 0.648), whereas the specificity of PET was 15.4% higher than that of CT/MRI (P = 0.188) and 7.7% higher than that of clinical palpation (P = 0.482). The accuracy of 18F-FDG PET, CT/MRI, and clinical palpation for the identification of cervical nodal metastases was 85.0%, 70.0% and 75.0% respectively. CONCLUSIONS: The sensitivity, specificity and accuracy of PET for the detection of cervical nodal metastases was higher than that of CT/MRI and clinical palpation. Although the results did not show a statistically significant difference, PET can still serve as a supplementary method for the identification of nodal metastases of head and neck cancer.