Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma

Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.

Secular trend analysis of lung cancer incidence in Sihui city,China between 1987 and 2011

Background:With industrial and economic development in recent decades in South China,cancer incidence may have changed due to the changing lifestyle and environment.However,the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear.The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.Methods:Joinpoint regression analysis and the age-period-cohort(APC) model were used to analyze the lung cancer incidence trends in Sihui,Guangdong province,China between 1987 and 2011,and explore the possible causes of these trends.Results:A total of 2,397 lung cancer patients were involved in this study.A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period.Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period,a sharp acceleration was observed in males starting in 2005.The full APC model was selected to describe age,period,and birth cohort effects on lung cancer incidence trends in Sihui.The age cohorts in both sexes showed a continuously significant increase in the relative risk(RR)of lung cancer,with a peak in the eldest age group(80-84 years).The RR of lung cancer showed a fluctuating curve in both sexes.The birth cohorts identified an increased trend in both males and females;however,males had a plateau in the youngest cohorts who were born during 1955-1969.Conclusions:Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts.Social aging,smoking,and environmental changes may play important roles in such trends.

Subtype distribution and long-term titer luctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China:a cohort study

Background: Serum immunoglobulin A antibodies against Epstein–Barr virus(EBV), viral capsid antigen(VCA?Ig A) and early antigen(EA?Ig A), are used to screen for nasopharyngeal carcinoma(NPC) in endemic areas. However, their routine use has been questioned because of a lack of specificity. This study aimed to determine the distributions of different subtypes of antibody and to illustrate how the natural variation patterns affect the specificity of screening in non?NPC participants.Methods: The distribution of baseline VCA?IgA was analyzed between sexes and across 10?year age groups in 18,286 non?NPC participants using Chi square tests. Fluctuations in the VCA?IgA level were assessed in 1056 non?NPC participants with at least two retests in the first 5?year period(1987–1992) after the initial screening using the Kaplan–Meier method.Results: The titers of VCA?Ig A increased with age(P < 0.001). Using a previous serological definition of high NPC risk, nasopharyngeal endoscopy and/or nasopharyngeal biopsy would be recommended in 55.5% of the non?NPC partici?pants with an initial VCA?Ig A?positive status and in 20.6% with an initial negative status during the 5?year follow?up. However, seroconversions were common; 85.2% of the participants with a VCA?Ig A?positive status at baseline con?verted to negative, and all VCA?Ig A?negative participants changed to positive at least once during the 5?year follow?up. The EA?Ig A status had a high seroconversion probability(100%) from positive to negative; however, it had a low probability(19.6%) from negative to positive.Conclusions: Age? and sex?specific cutoff titer values for serum anti?EBV antibodies as well as their specific titer fluc?tuation patterns should be considered when defining high NPC risk criteria for follow?up diagnostics and monitoring.

Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma in the Chinese population

Salivary gland carcinomas(SGCs)are rare malignancies that remain poorly understood owing to their low incidence(Matsuba et al.,1986b;Liu et al.,2012).As per GLOBOCAN 2018.52.800 new cancers arising from salivary glands were estimated to be diag-nosed across the world that year.Because of their high propensity to invade local and perineural structures.

Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma

Background:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy(IMRT)as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma(NPC),but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients.Endoscopic nasopharyngectomy(ENPG)was successfully applied in recurrent NPC with radiation free and relatively low medical costs.In this study,we examined whether ENPG could be an effective treatment for localized stage I NPC.Methods:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center.Simultaneously,the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort.The survival outcomes,quality of life(QOL),and medical costs between two groups were compared.Results:After a median follow-up of 59.0 months(95%CI 53.4-64.6),no death,locoregional recurrence,or distant metastasis was observed in the 10 patients treated with ENPG.The 5-year overall survival,local relapse-free survival,regional relapse-free survival,and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients(100%vs.99.1%,100%vs.97.7%,100%vs.99.0%,100%vs.97.4%,respectively,P>0.05).In addition,compared with IMRT,ENPG was associated with decreased total medical costs($4090.42±1502.65 vs.$12620.88±4242.65,P<0.001)and improved QOL scores including dry mouth(3.3±10.5 vs.34.4±25.8,P<0.001)and sticky saliva(3.3±10.5 vs.32.6±23.3,P<0.001).Conclusions:ENPG alone was associated with promising long-term survival outcomes,low medical costs,and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy.However,the application of ENPG should be prudent,and prospective clinical tri-als were needed to further verify the results.

Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study

Background:Famitinib is a tyrosine kinase inhibitor against multiple targets,including vascular endothelial growth factor receptor 2/3,platelet-derived growth factor receptor,and stem cell factor receptor(c-kit).Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers.We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy(CCRT)in patients with locoregionally advanced nasopharyngeal carcinoma(NPC).We also evaluated the feasibility of contrast-enhanced ultrasound(D-CEUS)as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.Methods:The trial was conducted in subjects with stage III or IVa-b NPC using a 3+3 design of escalating fami-tinib doses.Briefly,subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT.D-CEUS of the neck lymph nodes was performed at day 0,8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy.End points included safety,tolerability and anti-tumour activity.Results:Twenty patients were enrolled(six each for 12.5,16.5 and 20 mg and two for 25 mg).Two patients in the 25 mg cohort developed dose-limiting toxicities,including grade 4 thrombocytopenia and grade 3 hypertension.The most common grade 3/4 adverse events were leukopenia,neutropenia and radiation mucositis.D-CEUS tests showed that more than 60%of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone,and the parameter response was associated with disease improvement.In the famitinib monotherapy stage,three patients(15%)showed partial responses.The complete response rate was 65%at the completion of treatment and 95%3 months after the treatment ended.After a median follow-up of 44 months,the 3-year progression-free survival(PFS)and distant metastasis-free survival were 70%and 75%,respectively.Subjects with a decrease of perfusion parameter response,such as peak intensity decreased at least 30%after 1 week of famitinib treatment,had higher 3-year PFS(90.9%vs.44.4%,95%CI 73.7%-100%vs.11.9%-76.9%,P<0.001)than those with an increase or a reduction of less than 30%.Conclusions:The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC.D-CEUS is a reliable and early measure of efficacy for famitinib therapies.Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.