Carbon segregation using metal substrates has been given increasing attention as an alternative graphene growth method due to its reduced temperature. However, not every metal behaves in the same ...manner during the process, hence it is imperative to study their effectiveness when using this growth method. In this paper, few-layer graphene was fabricated on metal substrates with an energetic carbon source supplied by pulsed laser deposition. The ability of Ni, Cu, Co and Fe thin films to form graphene through segregation was investigated. Graphene was fabricated on Ni and absent in Cu, Co and Fe under a specific cooling profile. This was attributed to either low solubility of carbon in Cu and Fe or low carbon diffusion coefficient in Co. However, by adjusting the cooling rate to cater to the carbon diffusion coefficient of Co, low defect few-layer graphene with large substrate coverage was obtained. The results showed that when using PLD, a metal with sufficient carbon solubility is desired over its catalytic ability. The reasons behind the observed phenomena are also discussed.
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► The viability of Ni, Co, Cu and Fe metals to fabricate graphene by segregation was studied. ► Limited amount of energetic carbon was supplied with solid carbon target. ► Carbon solubility critically affects the successful formation of graphene. ► Cooling rate is another critical parameter for such solid-state reaction. ► Low defect graphene was fabricated on Co as confirmed by Raman spectroscopy.
A retrospective study was performed to correlate the expression of epidermal growth factor receptor (EGFR) with treatment outcome in advanced stage nasopharyngeal carcinoma (NPC).
The study ...population comprised 54 of 92 patients with American Joint Committee on Cancer Stage III-IV NPC with sufficient pretreatment tumor biopsy specimens for study. Immunohistochemical staining was performed to evaluate the extent and intensity of EGFR expression. All patients were treated by induction chemotherapy with two to three cycles of cisplatin 60 mg/m
2 and epirubicin 110 mg/m
2 every 3 weeks followed by radiotherapy. The median follow-up time was 52 months for all patients and 99 months for surviving patients.
EGFR expression was present in 89% of cases. EGFR intensity was negative in 11%, weak in 43%, moderate in 13%, and strong in 33%. The EGFR extent was <5% in 15%, ≥5% but <25% in 13%, and ≥25% in 72%. No correlation was found between EGFR expression and T stage, N stage, stage group, nodal size, gender, and age. No statistically significant differences in chemotherapy response rates were found in patients with different EGFR intensity and extent. EGFR extent ≥25% was associated with a significantly poorer treatment outcome. The 5-year disease-specific survival, relapse-free survival, locoregional relapse-free, and distant metastasis-free rate in patients with EGFR extent ≥25% was 48%, 36%, 60%, and 55%, respectively. The corresponding rates in patients with EGFR extent <25% were 86%, 80%, 93%, and 86%. The differences were all statistically significant, except for distant metastasis. No statistically significant differences in relapse-free and disease-specific survival rates were found among patients with differing EGFR intensity. In multivariate analysis, EGFR extent was the only independent factor that predicted for disease relapse, locoregional failure, and cancer death.
Our study results showed that EGFR expression was common in advanced stage NPC, and the expression did not correlate with tumor or nodal stage. Correlative analysis showed that EGFR extent was a strong, independent prognostic factor that determined locoregional control, relapse-free survival, and disease-specific survival in Stage III-IV NPC treated with induction chemotherapy and radiotherapy. Our findings suggest that EGFR expression status can identify a subgroup of patients within advanced stage disease that will have a poor outcome after induction chemotherapy and radiotherapy. Whether this patient subgroup will benefit from an alternate treatment strategy and anti-EGFR–targeted treatment requires additional studies.
To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC).
Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were ...eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B.
Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009).
An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of ...acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination.
This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed.
Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval CI, 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated.
There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.
Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in ...loco-regionally advanced nasopharyngeal carcinomas (NPCs).
Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R
between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS.
PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval CI = 0.93 to 0.94) and at the trial level (R
= 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R
= 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R
= 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R
= 0.78, 95% CI = 0.33 to 1.00).
PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier.
Objective
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose–response ...relationship between duration of football played and CTE risk and severity.
Methods
In a convenience sample of 266 deceased American football players from the Veterans Affairs–Boston University–Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.
Results
In total, 223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played were associated with having CTE (odds ratio OR = 1.30 per year played, 95% confidence interval CI = 1.19–1.41; p = 3.8 × 10−9) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07–1.22; p = 3.1 × 10−4). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio LR = 0.102, 95% CI = 0.100–0.105) and were 10 times as likely to have played >14.5 years (positive LR = 10.2, 95% CI = 9.8–10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.
Interpretation
The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent. ANN NEUROL 2020;87:116–131
The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest ...survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis.
For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524.
The network comprised 28 trials and included 8214 patients (6133 74·7% were men, 2073 25·2% were women, and eight 0·1% had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2–13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59–0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69–0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75–1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%).
The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma.
Institut National du Cancer and Ligue Nationale Contre le Cancer.
Abstract Background and purpose To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma. Materials ...and methods From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF + C/AF/AF + C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil. Results The AF + C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p = 0.013), the AF group (56%; p = 0.001) and the CF + C group (65%; p = 0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p = 0.25). Deaths due to cancer progression decreased (7% vs. 33%; p = 0.011) but deaths due to incidental causes increased (9% vs. 2%; p = 0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p = 0.058). Conclusions Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain.
Background
In early‐stage non–small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for ...recurrence after curative intent therapy. This study aimed to risk stratify patients with early‐stage NSCLC via a personalized, tumor‐informed multiplex polymerase chain reaction (mPCR) next‐generation sequencing assay.
Methods
This retrospective cohort study included patients with stage I–III NSCLC. Recruited patients received standard‐of‐care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole‐exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient‐specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single‐nucleotide variants in plasma samples.
Results
The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence‐free survival (RFS; hazard ratio HR, 3.54; 95% confidence interval CI, 1.00–12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0–12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63–158.9; p < .0001).
Conclusions
ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early‐stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.
Circulating tumor DNA (ctDNA) detection before surgical resection was strongly associated with a high risk of relapse in early‐stage non–small cell lung cancer in a large unique Asian cohort. In addition, ctDNA detection longitudinally after surgery identified patients who recurred, with ctDNA positivity preceding radiological findings.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE) radiotherapy improved tumor control and ...survival in GBM patients.
We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated.
Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS) of patients who received DE radiotherapy was 15.2 months (95% confidence interval CI =11.0-18.6), while median OS of the latter cohort was 18.4 months (95% CI =12.5-31.4, P=0.253). Univariate analyses of clinical and dosimetric parameters among the DE cohort demonstrated a trend of longer progression-free survival, but not OS, with incremental radiation doses to the ipsilateral SVZ (hazard ratio HR =0.95, 95% CI =0.90-1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR =0.98, 95% CI =0.97-1.00, P=0.017).
DE radiotherapy did not improve survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy target volume for patients with GBM requires prospective validation.
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