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Purpose This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. Patients and Methods Patients were enrolled to receive cetuximab (500 mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. Results Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%–48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%–36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. Conclusion Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. Implications for Practice This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.

PURPOSE To explore whether volumetric measurements of 3D-CUBE sequences based on baseline and early treatment time can predict neoadjuvent chemotherapy (NCT) efficacy of locally advanced rectal cancer (LARC). MATERIAL AND METHOD 73 patients with LARC were enrolled from February 2014 to January 2018. All patients underwent MRIs during the baseline period before NCT (BL-NCT) and the first month of NCT (FM-NCT), and tumor volume (TV) was measured using 3D-CUBE, and tumor volume reduction (TVR) and tumor volume reduction rate (TVRR) were calculated. In addition, tumor invasion depth, tumor maximal length, range of tumor involvement in the circumference of intestinal lumen and distance from inferior part of tumor to the anal verge were measured using baseline high-spatial-resolution T2-weighted MRIs. All patients were categorized into sensitive and insensitive groups based on post-surgical pathology after completion of the full courses of NCT. The receiver operating characteristic (ROC) curve was used to analyze the value of different MRI parameters in predicting efficacy of NCT. RESULTS Statistically significant differences in TV of BL-NCT, TVR and TVRR from BL-NCT to FM-NCT were detected between sensitive and insensitive groups (P

To investigate the value of MRI with CUBE sequence in early evaluation of the efficacy of neoadjuvant therapy (NAT) for locally advanced rectal cancer.Inclusion criteria: (1) rectal cancer proven by biopsy; (2) locally advanced rectal cancer (T3-4 or positive lymph nodes) with distance from lower edge of tumor to anal verge within 12 cm diagnosed by MRI before NAT; (3) acceptance of NAT treatment regulations and completion of NAT; (4) completion of routine MRI scan and CUBE scan before and after 2-course NAT chemotherapy (including new neoadjuvant chemotherapy and chemoradiotherapy); (5) completion of surgery 6-8 weeks after NAT; (6) exclusion of any previous NAT due to rectal malignant tumor or other tumors; (7) exclusion of poor image quality of preoperative routine MRI insufficient for rectal cancer staging or of CUBE image insufficient for tumor volume measurement. Fifty patients with advanced local rectal cancer were recruited in our hospital from February 2014 to January 2016. All the patients underwent MRI before and after 2-course neoadjuvent therapy. Tumor volume on CUBE were measured and the volume changes were calculated: volume difference= pre-treatment volume-post-treatment volume, volume change rate= (pre-treatment volume-post-treatment volume)/ pre-treatment volume. All the patients were categorized into sensitive and non-sensitive group according to postsurgical pathology. Comparisons were made between both groups before and after therapy. ROC curve was used to evaluate the value of CUBE-associated parameters in predicting the efficacy of rectal cancer.Among enrolled 50 patients with rectal cancer, 31 were male and 19 were female, with mean age of 49.1 years (range 21 to 70 years). T-staging by MRI before NAT was T2N1-2 in 1 case, T3 in 43 cases, T4 in 6 cases. The number of patients after NAT from tumor regression grading (TRG) 0 to TRG3 was 14, 13, 18, 5, respectively. The sensitive group and insensitive group were 45 cases and 5 cases. Mean tumor volume before and after preoperative 2-course NAT was 18.70 (4.14 to 91.77) cmMRI CUBE can predict the efficacy of NAT for early rectal cancer patients accurately and sensitively through the detection of tumor volume change before and after NAT.

99 Background: Conversion therapy for unresectable colorectal liver metastases (LM) can downsize tumours and create a situation where the patient has no evidence of disease (NED). We assessed the effectiveness of cetuximab plus mFOLFOXIRI or mFOLFOXIRI in this setting. Methods: FOCULM was a prospective 2:1 controlled, multicenter, phase II trial. Given no free drugs offered and the patients' affordability for cetuximab, the study design has been amended from randomization to non-randomization since September, 2016. Patients with unresectable LM were assigned to receive cetuximab (500mg/m2) plus mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 165 mg/m2, folinic acid 400 mg/m2, 5-fluorouracil 2800mg/m2 46h infusion, every 2 weeks) (group A) or mFOLFOXIRI (group B). Primary endpoint was the rate of NED achieved, secondary endpoints were ORR, resection rate, the rate of local and ablative treatment (LAT), OS, PFS and DpR. Results: From February 2014 to July 2019, 114 patients were enrolled at 6 centers in China and 101 patients were in the ITT population (67 group A, 34 group B). Treatment groups were generally well balanced, although more patients with ≥5 LM were in group A. The rate of NED achieved was 62.7% in group A and 38.2% in group B (P = 0.020). At a median follow-up of 19.4 months, patients in group A had significantly prolonged the mOS, increased ORR, the rate of LAT and DpR compared with those in group B (Table). Patients with NED achieved yielded a significant survival benefit, whether in group A (Not reached vs. 49.4 months; P = 0.001) or group B (Not reached vs. 25.1 months; P = 0.007). Conclusions: The addition of cetuximab to a mFOLFOXIRI in patients with RAS/BRAF wild-type unresectable LM colorectal cancer significantly improved the rate of NED achieved, ORR and OS. Clinical trial information: NCT02063529. [Table: see text]

NASICON-type Na 3 V 2 (PO 4 ) 2 F 3 is employed as a promising cathode for sodium-ion batteries in order to explore the ion-migration mechanism and diffusion capability. Two kinds of Na sites, namely Na(1) site and Na(2) site exist in the crystal structure per formula unit to accommodate a total of three sodium ions. The ion at Na(2) site with half occupation extracts first and inserts the last due to its high chemical potential, while the whole extraction/insertion of two ions between 1.6 and 4.6 V vs. Na + /Na can produce three plateaus in charge/discharge processes because of the reorganization of ions. The first discharge capacity of 111.6 mAh g −1 with retention of 97.6% after 50 cycles could be obtained by electrochemical testing at 0.091C. Electrochemical activation and/or structural reorganization of the system by cycling could improve the diffusion coefficient of sodium with a comparatively large magnitude of 10 −12 cm 2 s −1 , though many influences on the resistance factors also can be attributed to the cycling process. Such work is of fundamental importance to the progression of sodium-based batteries to be fully realized and be implemented over existing Li-ion based batteries.

The NASICON-type Na3V2(PO4)3 (NVP) cathode material is investigated in an aqueous sodium-ion battery, which is explored by using a three-electrode system. The battery behaviors and capacitive properties of this electrode system are critically investigated by using 1 m Li2SO4, Na2SO4, and K2SO4 electrolytes, with an optimal performance found to arise in Na+-based electrolyte, which exhibits a capacitance of 209 Fg−1 at 8.5 C as well as enhanced ion diffusion. Larger, hydrated Li+ is less able to diffuse into the network of NVP, and the low conductivity and mobility leads to near noncapacitive behavior. In the case of K+-based electrolyte, NVP presents asymmetric cyclic voltammograms, owing to weak solvation and the high conductivity of K+, making the ions more easily able to form electric double-layer capacitance on the surface or pores of NVP, rather than insert into the network. The equivalent circuit based on electrochemical impedance spectroscopy result is analyzed to account for the electrochemical insertion behavior of Na+ into NVP, involving ion transfer in electrolyte solution, ion diffusion from the electrolyte to the electrode surface, as well as charge transfer and ion diffusion in the electrode solid.

Na3V2(PO4)2F3 with a NASICON-type structure is shown to be synthesised with the particle surface found to be coated with amorphous carbon with its thickness in the range of 25–32 nm. The crystallographic planes (hkl) are labelled according to Density Functional Theory (DFT) calculations towards the as-prepared Na3V2(PO4)2F3. The performances of Na3V2(PO4)2F3 have been investigated in lithium- and sodium-ion batteries, exhibiting a specific capacity of 147 mA h g−1 with an average discharge plateau around 4 V vs. Li+/Li, and 111.5 mA h g−1 with three discharge plateaus in sodium-ion batteries. A predominant Li ion insertion mechanism is verified by comparing the redox potentials from CV and charge/discharge curves. It is found that the main migration from/into the crystallographic sites of Na3V2(PO4)2F3 of Li ions is favoured to obtain satisfactory properties by a two-step process, while the Na ions are found to require three steps. The stable and three-dimensional open framework of Na3V2(PO4)2F3 is considered to be vital for the excellent C-rate and cycling performances, as well as the fast ion diffusion with a magnitude of 10−11 cm2 s−1, which could demonstrate that Na3V2(PO4)2F3 is a multifunctional dual cathode for both lithium and sodium ion batteries and capable to be a promising candidate in the construction of high-energy batteries.

To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

Ion occupation and migration pathways are investigated to explore the ion-migration mechanism of Na3V2(PO4)3 with the help of first principles calculations. Na3V2(PO4)3 with a NASICON framework generates high performances as a cathode material in sodium-ion batteries.

The goal of the present study was to investigate whether p53 antibodies (Abs) could be a relevant marker for papillary thyroid carcinoma (PTC). Three types of enzyme-linked immunosorbent assay (ELISA) methods were developed for the detection of p53 Abs, including p53-ELISA, phage-SS-ELISA, and phage-SP-ELISA. A total of 304 patients, including 117 cases with thyroid adenoma and 187 PTC patients, were enrolled in this study. Expression of p53 protein and mutation in BRAF gene were evaluated in paraffin-embedded tissue from 44 patients with PTC, in order to elucidate their correlations with the presence of p53 Abs. Compared with p53-ELISA and phage-SS-ELISA, phage-SP-ELISA presented the highest detection efficiency of p53 Abs in patients with PTC, and a combination of these three ELISA systems could make the detection of p53 Abs more sensitive than using each of the individual ELISA methods. Furthermore, p53 Abs was positively associated with clinical stage (P = 0.044), node metastasis (P = 0.010), and p53 protein accumulation (P = 0.019). These results indicate that serum p53 Abs could be a useful marker for PTC.

Objective. This study aimed to compare the accuracy of rectal cancer restaging after neoadjuvant therapy with 3D CUBE sequence with 2D T2-weighted fast spin-echo (FSE) sequence. Methods. This retrospective study comprised 72 patients with rectal cancer confirmed by colonoscopy and biopsy. After neoadjuvant therapy, all patients underwent pelvic magnetic resonance imaging (MRI) examination at 1.5T MRI sequences including a single coronal 3D CUBE T2-weighted FSE sequence with 1.4 mm thickness and a 2D T2-weighted FSE sequence in the sagittal, coronal and axial planes with 5 mm thickness. The total acquisition time of the two sequences was recorded. Results were compared with postsurgical pathology (gold standard). The diagnostic accuracy was evaluated; and receiver operating characteristic (ROC) curves and the area under the curves (AUC) were calculated. Results. The T category staging accuracy of 3D T2WI and 2D T2WI was 81.9% and 72.2%, respectively, for reviewer 1 and 86.1% and 75.0% for reviewer 2. The AUC of 3D was higher than that of 2D (0.878 vs. 0.783 for reader 1 and 0.905 vs. 0.796 for reader 2; both P < 0.05) when judging whether the tumor broke through the muscle layer. There was no significant difference between 3D and 2D in judging whether lymph nodes were malignant (AUC 0.719 vs. 0.698 for reader 1 and 0.740 vs. 0.698 for reader 2; both P > 0.05). There were no significant differences in the visibility of the rectal wall layer, tumor lesion and the overall image quality (all P > 0.05). Compared with 2D sequences, the 3D sequence had shorter acquisition time and higher signal intensity ratio (both P < 0.05). Conclusion. 3D CUBE T2-weighted sequences offer better diagnostic accuracy in rectal cancer restaging after neoadjuvant therapy when compared with 2D T2-weighted FSE sequences; it has a shorter scanning time and more versatility of orientation reconstruction.