Does three cycles of neoadjuvant chemotherapy prior to concurrent chemoradiotherapy provide benefits for all childhood patients with locoregionally advanced nasopharyngeal carcinoma?

BACKGROUND: Adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) is the main strategy in treatment of children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC). Yet, an optimal number of NAC cycles remains unknown. We aimed to optimize the NAC cycle and potentially contribute to clinical decision making for the individual treatment of CA-LANPC. PATIENTS AND METHODS: Utilizing an NPC-specific database through an acknowledged big-data information system at our center, we identified 143 CA-LANPC treated with NAC followed by CCRT between September 2007 through April 2018. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict disease-free survival (DFS). The clinical benefits of NAC cycles (two cycles vs three cycles) were assessed in each risk group. RESULTS: Independent factors derived from multivariable analysis to predict DFS were T stage (T1-3 vs T4) and plasma Epstein-Barr virus (EBV) DNA (< 4000 vs ≥ 4000 copies/mL) for risk stratification. Consequently, 87 (61%) participants were classified as low-risk group (T1-3 with low or high EBV DNA, and T4 with low EBV DNA) and the other 56 patients (39%) were classified as a high-risk group (T4 with high EBV DNA) through RPA, and corresponding 5-year DFS rates of 91.9% and 71.2%, respectively (p = 0.001). Among the high-risk group, patients receiving three cycles of NAC had statistically significant improvement in 5-year DFS over those who received two cycles of NAC (86.7% vs 59.1%; p = 0.020), while the survival benefit of three cycles NAC for low-risk groups were not observed (94.7% vs 89.7%; p = 0.652). CONCLUSIONS: We found three cycles of NAC with CCRT was a positive prognostic indicator for improved DFS for the high-risk group among CA-LANPC. However, whether low-risk patients could benefit from three cycles NAC needs further study.

Increasing Embryonic Morphogen Nodal Expression Suggests Malignant Transformation in Colorectal Lesions and as a Potential Marker for CMS4 Subtype of Colorectal Cancer.

Nodal, an embryonic morphogen in TGF-ß family, is related with tumorigenicity and progression in various tumors including colorectal cancer (CRC). However, the difference of Nodal expression between CRC and colorectal polyps has not yet been investigated. Besides, whether Nodal can be used as a marker for consensus molecular subtype classification-4 (CMS4) of CRC is also worth studying. We analyzed Nodal expression in patients of CRC (161), high-grade intraepithelial neoplasia (HGIN, 28) and five types of colorectal polyps (116). The Nodal expression difference among groups and the association between Nodal expression and clinicopathological features were analyzed. Two categories logistic regression model was used to predict the odds ratio (OR) of risk factors for high tumor-stroma percentage (TSP), and ROC curve was used to assess the diagnostic value of Nodal in predicting high TSP in CRC. We found that Nodal expression was significantly elevated in CRC and HGIN (p < 0.0001). The increased expression of Nodal was related with high TSP, mismatch repair-proficient (pMMR) status, lymph node metastasis and advanced AJCC stage (p < 0.05). Besides, Nodal expression was the only risk factor for high TSP (OR = 6.94; p < 0.001), and ROC curve demonstrated that Nodal expression was able to efficiently distinguish high and low TSP. In conclusion, different expression of Nodal between CRC/HGIN and benign lesions is suggestive of a promoting role for Nodal in colorectal tumor progression. Besides, Nodal might also be used as a potential marker for CMS4 subtype of CRC.

Optimal cumulative cisplatin dose during concurrent chemoradiotherapy among children and adolescents with locoregionally advanced nasopharyngeal carcinoma: A real-world data study.

PURPOSE: To identify an optimal cumulative cisplatin dose along with concurrent chemoradiotherapy (CC-CCD) for children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC) using real-world data. MATERIALS AND METHODS: Using an NPC-specific database at our center, 157 patients younger than 19 years old with non-disseminated CALANPC and receiving neoadjuvant chemotherapy (NAC) plus cisplatin-based concurrent chemoradiotherapy (CCRT) were enrolled. Confounding factors were controlled by conducting propensity score matching analysis. Primary endpoints include disease-free survival (DFS) and distant metastasis-free survival (DMFS). RESULTS: The optimal threshold for CC-CCD with respect to DFS was 160 mg/m2 based on recursive partitioning analyses (RPA). Therefore, a uniform threshold of 160 mg/m2 (≥160 vs. <160 mg/m2) was selected to classify patients between high and low CC-CCD groups for survival analysis. Patients receiving low CC-CCD showed a significant decrease in 5-year DFS (76.6% vs 91.3%; P = 0.006) and DMFS (81.3% vs 93.5%; P = 0.009) compared to those receiving high CC-CCD. Multivariate analyses indicated that high CC-CCD as an favorable prognostic influence for DFS (P = 0.007) and DMFS (P = 0.008). Further matched analysis identified 65 pairs in both high and low CC-CCD groups. In the matched cohort, high CC-CCD was still identified as a favorable factor for prognosis in DFS (HR, 0.23; 95% CI, 0.08-0.70; P = 0.010) and DMFS (HR, 0.23; 95% CI, 0.06-0.82; P = 0.023). CONCLUSION: CC-CCD exerts significant treatment effects and 160 mg/m2 CC-CCD may be adequate to provide antitumor effects for CALANPC receiving NAC plus CCRT.

Subcutaneous tunneling technique to improve outcomes for patients undergoing chemotherapy with peripherally inserted central catheters: a randomized controlled trial.

OBJECTIVE: To compare the value of the subcutaneous tunneling technique versus the normal technique in improving the outcomes of patients undergoing chemotherapy with peripherally inserted central catheters (PICCs). METHODS: One hundred thirty patients were randomly divided into an experimental group (subcutaneous tunneling technique) and control group (normal technique) according to the PICC placement technique, and clinical data were compared between the groups. RESULTS: In total, 129 PICCs were successfully inserted. Compared with the control group, the experimental group had a lower occurrence of complications after placement (especially catheter dislodgement: 3.1% vs. 15.4%, venous thrombosis: 3.1% vs. 15.4%, and wound oozing: 14.1% vs. 27.7%), lower occurrence of unscheduled PICC removal (3.1% vs. 13.8%), greater comfort during placement (14.16 ± 2.21 vs. 15.09 ± 2.49 on a scale ranging from 6 to 30 points, with higher scores indicating lower degrees of comfort), and lower costs of PICC maintenance (median (interquartile range) per-day maintenance cost: 13.90 (10.99-32.83) vs. 15.69 (10.51-57.46) Yuan). The occurrence of complications and amount of bleeding during placement were not significantly different between the two groups. CONCLUSIONS: The subcutaneous tunneling technique can improve PICC placement by reducing complications and costs of maintenance with better patient comfort during placement.

Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma.

BACKGROUND: The appropriate treatment strategy for T1N0M0 lung large cell neuroendocrine carcinoma (LCNEC) was not well illustrated. We evaluated the efficacy of different surgery types and adjuvant therapy on patients with T1N0M0 LCNEC. METHODS: Patients diagnosed T1N0M0 LCNEC from 2004 to 2016 were identified in the surveillance, epidemiology, and end results (SEER) database. Clinical characteristics, treatment and survival data were collected. The efficacy of surgery type and adjuvant therapy stratified by tumor size was assessed. Overall survival(OS) was evaluated by the Kaplan-Meier method, and relevant survival variables were identified by the Cox proportional hazard model. RESULTS: From 2004 to 2016, 425 patients were included in this study, 253 (59.5%) patients received lobectomy, and 236 (55.5%) patients had 4 or more lymph nodes removed. Patients received lobectomy had better survival than those received sublobar resection(P=0.000). No matter tumor size less than 2 cm or 2 to 3 cm, lobectomy was significantly prolonged survival. Compared with no lymph nodes removed, lymph nodes dissection was associated with more remarkable OS(P<0.000). 4 or more regional lymph nodes dissection predicted better OS compared with 1 to 3 regional lymph nodes dissection(P=0.014). After surgery, adjuvant chemotherapy did not contribute to extended survival in patients with tumor less than 2 cm(P=0.658), and possibly for tumor 2 to 3 cm(P=0.082). Multivariate analysis showed that age and lobectomy were independent prognostic factors(P=0.000). CONCLUSION: Our results suggest that lobectomy and lymph nodes dissection were associated with significantly better survival. Extensive regional lymph node dissection(4 or more) was more effective in prolonging survival than 1 to 3 lymph nodes dissection. Adjuvant chemotherapy was not associated with extended survival for tumor less than 2 cm, and possibly for tumor 2 to 3 cm.

Habitual consumption of alcohol with meals and lung cancer: a Mendelian randomization study.

BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.

The wormlike micelles formed using an ionic liquid surfactant and polar organic solvents at low temperature without additives and their lubricant properties.

Wormlike micelles (or reverse wormlike micelles) are flexible cylindrical chains that are normally formed in water (or a nonpolar organic solvent) at 25.0 °C or above; the formation of wormlike micelles at lower temperatures is rare. Here, we have reported wormlike micelles formed at low temperature using an ionic liquid surfactant (1-octadecyl-3-nonyl imidazolium bromide) in polar organic solvents (including 1,3-propanediol, 1,2-propylene glycol, N,N-dimethylformamide, and glycerol/1,2-propylene glycol mixture) in the absence of any additives. The viscoelasticity and morphology of the wormlike micelles were studied using rheology, small-angle X-ray scattering, and cryo-transmission electron microscopy. The viscoelastic properties of the wormlike micelles in polar solvents are affected by the solvent type (or the weight ratio of glycerol to 1,2-propylene glycol), surfactant concentration, and temperature. Moreover, the G' and G'' crossover twice in the dynamic curves, which is different from the case in water. The first crossover (at low frequency) corresponds to the relaxation time for the alkyl chains to disentangle from the transient network, and the second crossover (at high frequency) is related to the segmental motion of the chains. Furthermore, the tribological performance of these wormlike micelles is investigated at low temperature. It is found that the protective film (formed by the physical adhesion of the wormlike micelles on the surface of friction disk pair) and the tribochemical reaction together lead to good antifriction and antiwear performance, which indicates the application prospects of these wormlike micelles in low-temperature lubrication.

Changes in colorectal cancer incidence by site and age from 1973 to 2015: a SEER database analysis.

Previous studies have reported incidence and mortality declines for colorectal cancer (CRC). We evaluated recent temporal trends of colorectal cancer in the United States for the last 4 decades. Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified primary CRCs diagnosed between 1973 and 2015. Temporal changes were evaluated by 6-year time periods. Age-adjusted incidence rates and annual percentage change (APC) for CRC were calculated by site and gender. Age-standardized relative survival rates were also evaluated. We identified 878,632 CRC patients, 51% of whom were men. For both genders, the proportions of new diagnoses of right-sided colon cancer (RCC) remained relatively stable, with the APC of - 0.8 and - 0.6 for the male and the female, respectively. There was a relative increase in RCC for the younger aged group (< 49 years). In contrast, the proportions of left-sided colon cancer (LCC) and rectosigmoid-cancer (RSC) decreased significantly over time. For those aged 0-49, the age adjusted incidence rates showed a small increase (in both genders), whereas age-adjusted incidence rates declined for those aged 50-64 and > 65 (in both genders). Our study showed near significance in the decline of CRC mortality rates in this population, except the 1-year age-standardized survival of LCC and RSC, and the 5-year age-standardized RCC in females. There was a significant increase in RCC for the younger aged group (< 49 years). In contrast, the proportions of LCC and RSC decreased significantly over time.

Previous Use of Anti-Vascular Endothelial Growth Factor Receptor Agents Decreases Efficacy of Fruquintinib in Metastatic Colorectal Cancer Refractory to Standard Therapies.

PURPOSE: Fruquintinib is an anti-vascular endothelial growth factor receptor (VEGFR) agent. The FRESCO trial demonstrated that patients with metastatic colorectal cancer (mCRC) refractory to standard therapies could benefit from fruquintinib with tolerable adverse events (AEs). However, the efficacy and safety of fruquintinib in clinical practice has scarcely been reported, especially in patients with previous use of anti-VEGFR agents. METHODS: This retrospective study investigated the efficacy and safety of fruquintinib in patients with mCRC between January 2019 and December 2019. Progression-free survival (PFS) and overall survival (OS) were assessed by a Kaplan-Meier analysis and log-rank test. A Cox regression model was performed to identify independent prognostic factors. RESULTS: A total of 46 patients were included. The median PFS and OS were 3.1 months (95% confidence interval [CI], 1.9-4.3 months) and 9.0 months (95% CI, 7.2-10.8 months), respectively. Patients previously treated with anti-VEGFR agents had shorter median PFS compared with those without previous use of anti-VEGFR agents (1.9 vs. 3.7 months, P = 0.006), while the median OS was similar between the two groups (8.5 vs. 9.0 months, P = 0.992). Multivariate analysis revealed that the neutrophil-lymphocyte ratio (NLR) was an independent prognostic factor in PFS (hazard ratio [HR], 2.230; 95% CI, 1.191-4.517, P = 0.014) and OS (HR, 4.221; 95% CI, 1.683-10.586; P = 0.002). The most common non-hematological and hematological AEs were hand-foot syndrome (37.0%) and anemia (39.1%), respectively. CONCLUSION: Fruquintinib was an effective third-line therapy in mCRC with tolerable AEs. Efficacy of fruquintinib was decreased in patients with previous use of anti-VEGFR agents. NLR was an independent prognostic factor in PFS and OS in patients treated with fruquintinib.

Safety and Efficacy of Long-Term Zoledronic Acid in Advanced Breast Cancer with Bone Metastasis in South China.

BACKGROUND: This retrospective study aimed to characterize the long-term (>24 months) safety profile of zoledronic acid (ZA). We aimed to investigate whether long-term ZA treatment had greater benefits than short-term treatment in patients from southern China with advanced breast cancer (ABC) with bone metastasis. Patients and Methods. A total of 566 metastatic breast cancer cases were included and divided into two groups according to the duration of ZA treatment. The included patients had at least one lytic bone lesion and had no skeletal-related events (SREs) prior to ZA therapy. The primary endpoint was to analyze the safety and long-term adverse effects, which covered osteonecrosis of jaws (ONJ), renal impairment, and hearing impairment. The second objective was to determine the efficacy of long-term ZA treatment by the incidence of SREs. RESULTS: Fifteen patients were diagnosed with ONJ (2.7%): nine in the short-term group (3.1%) and six in the long-term group (2.2%, P = 0.606). Five cases (0.9%) had renal function impairment: two in the short-term group (0.7%) and four in the long-term group (1.1%, P = 0.676). One patient (0.2%) in the long-term group had hearing impairment after 23 months of ZA treatment (0.4%, P = 0.482). In total, 103 cases in the short-term group (35.2%) and 138 cases in long-term group (50.5%) developed SREs (P < 0.001). The mean annual SRE rate was 0.3 in the short-term group (range, 0-3.1) versus 0.2 in the long-term group (0-1.0, P = 0.269). Subgroup analysis suggested that cases with non-load-bearing bone involvement and those who received systematic anticancer therapy without chemotherapy might benefit from long-term ZA treatment. Cox regression analysis indicated poor performance status, and nonvisceral organ involvement predicted high risk for SRE. CONCLUSIONS: The extension of ZA treatment did not increase the long-term adverse events and reduced the annual incidence of SREs beyond 24 months. Although longer treatment of ZA over 24 months appeared to be safe, further prospective investigation is required.

Follow-up study on symptom distress in esophageal cancer patients undergoing repeated dilation.

BACKGROUND: Repeated endoscopic probe dilatation is the most preferred treatment for esophageal stenosis which may cause high levels of symptom distress in the patient's home rehabilitation stage. AIM: To explore the changes in the symptom distress level and its correlation with the dilation effect in patients with esophageal carcinoma undergoing repeated dilations for lumen stenosis. METHODS: The difference (R2-R1) between the diameter of the esophageal stenosis opening (R1) of the patients before dilation (R1) and after dilation (R2) was calculated to describe the extent and expansion of the esophageal stenosis before and after dilation. The M.D. Anderson Symptom Inventory was used to describe the symptom distress level of patients with dilation intermittence during their stay at home and to explore the correlation between the dilation effect and symptom distress level. RESULTS: The diameter of the esophagus (R1) increased before each dilation in patients undergoing esophageal dilation (P < 0.05). The diameter (R2) increased after dilation (P < 0.05); the dilation effect (R2-R1) decreased with the number of dilations (P < 0.05). The total symptom distress score significantly increased with the number of dilations (P < 0.05). The symptom distress scores of the patients were negatively correlated (P < 0.05) with the previous dilation effect (R2-R1) and the esophageal diameter (R2) after the previous dilation. After the 1st to 4th dilations, the patient's symptom distress score was negatively correlated with the esophageal diameter (R12) before the next dilation, while there was no significant correlation (P > 0.05) with the other dilations. CONCLUSION: In patients who have undergone repeated dilations, better effect stands for lower symptom distress level and the increase in symptom distress has a prompt effect on the severity of the next occurrence of restenosis.

Prognostic significance of autophagy-related genes within esophageal carcinoma.

BACKGROUND: Several works suggest the importance of autophagy during esophageal carcinoma development. The aim of the study is to construct a scoring system according to the expression profiles of major autophagy-related genes (ARGs) among esophageal carcinoma cases. METHODS: The Cancer Genome Atlas was employed to obtain the esophageal carcinoma data. Thereafter, the online database Oncolnc ( http://www.oncolnc.org/ ) was employed to verify the accuracy of our results. According to our results, the included ARGs were related to overall survival (OS). RESULTS: We detected the expression patterns of ARG within esophageal carcinoma and normal esophageal tissues. In addition, we identified the autophagy related gene set, including 14 genes displaying remarkable significance in predicting the esophageal carcinoma prognosis. The cox regression results showed that, 7 ARGs (including TBK1, ATG5, HSP90AB1, VAMP7, DNAJB1, GABARAPL2, and MAP2K7) were screened to calculate the ARGs scores. Typically, patients with higher ARGs scores were associated with poorer OS. Moreover, the receiver operating characteristic (ROC) curve analysis suggested that, ARGs accurately distinguished the healthy people from esophageal carcinoma patients, with the area under curve (AUC) value of > 0.6. CONCLUSION: A scoring system is constructed in this study based on the main ARGs, which accurately predicts the outcomes for esophageal carcinoma.

A Carbon Fixation Enhanced Chlamydomonas reinhardtii Strain for Achieving the Double-Win Between Growth and Biofuel Production Under Non-stressed Conditions.

The stressed cultivations are widely used in microalgae R&D for the biofuel production with the repress on growth to a certain degree, which limits the overall productivity. The balance between the growth and energy storage compounds accumulation is a target needing the combination of both strain selection or construction and culture optimization. Here, an engineered strain of Chlamydomonas reinhardtii, in which the chloroplast type glyceraldehyde-3-phosphate dehydrogenase (cGAPDH) was overexpressed and named as P3-GAPDH, was cultured on the Algal Station platform. Compared with wild type (WT), C. reinhardtii CC137c, in Tris-acetate-phosphate (TAP) medium, the highest density of WT and P3-GAPDH were 1.23 ± 0.13 and 1.74 ± 0.09 g L-1 within 96 h, and the maximum biomass productivity was 24.30 ± 1.65 and 28.54 ± 1.43 mg L-1 h-1, respectively. In terms of the energy storage compounds, both carbohydrate and fatty acids content doubled in P3-GAPDH, from 0.13 ± 0.02 to 0.26 ± 0.04 g L-1 for carbohydrate and from 0.08 ± 0.01 to 0.16 ± 0.01 g L-1 for fatty acids, among which poly unsaturated fatty acids increased by 65.8%. Together with the continuous monitor of the chlorophyll fluorescence dynamics parameters F v/F m and F v'/F m' and pH of culture, enhanced Calvin cycle by overexpressed cGAPDH promoted the carbon conversion and subsequent energy storage compounds accumulation. C. reinhardtii P3-GAPDH strain showed the potential as a good chassis with high carbon conversion ability.

Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy.

BACKGROUND: This study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients. METHODS: We enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups. RESULTS: A total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35-33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36-0.91; p<0.05). CONCLUSIONS: HBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients. NAME OF THE TRIAL REGISTER: HAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/, identifier NCT02436044.