Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in ...nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC.
Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively.
Median follow-up was 5.0 years. The HR for PFS was 0.70 95% confidence interval (CI), 0.56-0.86;
= 0.0009; 9.3% absolute benefit at 5 years in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57-0.99;
= 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51-0.90;
= 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48-1.01;
= 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected.
This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control.
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The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed ...medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.≤2010 were 78.1% vs. 93.6% (P < 0.001), 92.3% vs. 98.9% (P < 0.001), 90.9% vs. 96.6% (P = 0.004) and 85.5% vs. 96.6% (P < 0.001), respectively. Three-year DFS, OS, LRRFS and DMFS for post-DNA >0 vs. = 0 were 49.9% vs. 88.5% (P < 0.001), 72.1% vs. 97.5% (P < 0.001), 86.6% vs. 94.3% (P = 0.019), and 60.5% vs. 93.3% (P < 0.001), respectively. Plasma EBV DNA remains a prognostic factor in IMRT era and should be incorporated into TNM staging to guide individualized treatment strategies in NPC.
The effect of socioeconomic factors on receipt of definitive treatment and survival outcomes in non‐metastatic head and neck squamous cell carcinoma (HNSCC) remains unclear. Eligible patients (n = 37 ...995) were identified from the United States Surveillance, Epidemiology and End Results (SEER) database between 2007 and 2012. Socioeconomic factors (i.e., median household income, education level, unemployment rate, insurance status, marital status and residence) were included in univariate/multivariate Cox regression analysis; validated factors were used to generate nomograms for cause‐specific survival (CSS) and overall survival (OS), and a prognostic score model for risk stratification. Low‐ and high‐risk groups were compared for all cancer subsites. Impact of race/ethnicity on survival was investigated in each risk group. Marital status, median household income and insurance status were included in the nomograms for CSS and OS, which had higher c‐indexes than the 6th edition TNM staging system (all P < 0.001). Based on three disadvantageous socioeconomic factors (i.e., unmarried status, uninsured status, median household income <US $65 394), the prognostic score model generated four risk subgroups with scores of 0, 1, 2 or 3, which had significantly separated CSS/OS curves (all P < 0.001). Low‐risk patients (score 0–1) were more likely to receive definitive treatment and obtain better CSS/OS than high‐risk patients (score 2–3). Chinese and non‐Hispanic black patients with high‐risk socioeconomic status had best and poorest CSS/OS, respectively. Therefore, marital status, median household income and insurance status have significance for predicting survival outcomes. Low‐risk socioeconomic status and Chinese race/ethnicity confer protective effects in HNSCC.
We built nomograms for CSS/OS and a prognostic score model for risk stratification based on validated socioeconomic factors, such as marital status, median household income and insurance status. Both nomograms had higher efficacies than the 6th edition TNM staging system, and the prognostic score model generated four risk subgroups with separated CSS/OS. Low‐risk socioeconomic status and Chinese race/ethnicity confer protective effects on patients with non‐matastatic HNSCC.
Abstract Background and purpose To evaluate the prognostic value of gross primary tumor volume (GTV-P) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). ...Methods and materials A total of 694 nonmetastatic and histologically proven NPC patients who underwent IMRT were retrospectively reviewed. Samples were split randomly into a training set ( n = 232) and a test set ( n = 462) to analysis. The receiver operating characteristic (ROC) curves were calculated to identify the cut-off point and test the prognostic validity of the GTV-P. The correlations between GTV-P and the American Joint Committee on Cancer (AJCC) disease stages were also analyzed. Results The 5-year disease-free survival (DFS), overall survival (OS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) rates for NPC patients with GTV-P < 19 vs. ⩾19 ml were 94.9% vs. 64.8%, 97.0% vs. 76.4%, 98.2% vs. 92.5% and 97.1% vs. 75.2%, respectively (all P < 0.05) in all patients. Multivariate analysis indicated GTV-P was an independent prognostic factor. The ROC curve verified that the predictive ability of T classifications was improved when combined with GTV-P ( P < 0.001). Conclusions GTV-P is an independent prognostic indicator for treatment outcome after IMRT, and significantly improves the prognostic validity of T classifications in NPC.
The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear.
Phase II-III clinical trials that evaluated ICI-based ...treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.
Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).
This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.
Little is known about the value of the nutritional risk screening 2002 (NRS2002) scale in nasopharyngeal carcinoma (NPC). We conducted a large‐scale study to address this issue. We employed a ...big‐data intelligence database platform at our center and identified 3232 eligible patients treated between 2009 and 2013. Of the 3232 (12.9% of 24 986) eligible patients, 469 (14.5%), 13 (0.4%), 953 (29.5%), 1762 (54.5%) and 35 (1.1%) had NRS2002 scores of 1, 2, 3, 4 and 5, respectively. Survival outcomes were comparable between patients with NRS2002 <3 and ≥3 (original scale). However, patients with NRS2002 ≤3 vs >3 (regrouping scale) had significantly different 5‐year disease‐free survival (DFS; 82.7% vs 75.0%, P < .001), overall survival (OS; 88.8% vs 84.1%, P = .001), distant metastasis‐free survival (DMFS; 90.2% vs 85.9%, P = .001) and locoregional relapse‐free survival (LRRFS; 91.6% vs 87.2%, P = .001). Therefore, we proposed a revised NRS2002 scale, and found that it provides a better risk stratification than the original or regrouping scales for predicting DFS (area under the curve AUC = 0.530 vs 0.554 vs 0.577; P < .05), OS (AUC = 0.534 vs 0.563 vs 0.582; P < .05), DMFS (AUC = 0.531 vs 0.567 vs 0.590; P < .05) and LRRFS (AUC = 0.529 vs 0.542 vs 0.564; P < .05 except scale A vs B). Our proposed NRS2002 scale represents a simple, clinically useful tool for nutritional risk screening in NPC.
We first evaluated the prognostic value of nutritional risk screen 2002 scale in nasopharyngeal carcinoma. We proposed a revised nutritional risk screen 2002 scale which performed better than the original scale.
ABSTRACT
The association of FRB 200428 with an X-ray burst (XRB) from the Galactic magnetar SGR 1935+2154 offers important implications for the physical processes responsible for the fast radio burst ...(FRB) phenomena. By assuming that the XRB emission is produced in the magnetosphere, we investigate the possibility that the FRB emission is produced by shock-powered synchrotron maser (SM), which is phenomenologically described with a number of free parameters. The observational constraints on the model parameters indicate that the model can in principle be consistent with the FRB 200428 observations, if the ejecta lunched by magnetar activities can have appropriate ingredients and structures and the shock processes occur on the line of sight. To be specific, a complete burst ejecta should consist of an ultra-relativistic and extremely highly collimated e± component and a sub-relativistic and wide-spreading baryonic component. The internal shocks producing the FRB emission arise from a collision between the e± ejecta and the remnant of a previous baryonic ejecta at the same direction. The parameter constraints depend on the uncertain spectrum and efficiency of the SM emission. While the spectrum is tentatively described by a spectral index of −2, we estimate the emission efficiency to be around 10−4 by requiring that the synchrotron emission of the shocked material cannot be much brighter than the magnetosphere XRB emission.
Background.
The objective of this study was to evaluate the prognostic value of the cumulative cisplatin dose (CCD) for long‐term survival outcomes after concurrent chemoradiotherapy (CCRT) in ...locoregionally advanced nasopharyngeal carcinoma (NPC).
Methods.
Patients were included in an open‐label phase III multicenter randomized controlled trial performed at seven institutions in China, and the 298 patients receiving CCRT only were assessed. Patient survival between different CCD groups were compared.
Results.
Median CCD for the 298 patients was 240 mg/m2 (range, 40–320 mg/m2); 113 (37.9%) patients received a CCD of <240 (≤200) mg/m2, and 185 (62.1%) received a CCD of ≥240 mg/m2. For CCD of ≥240 mg/m2 vs. <240 mg/m2, the estimated 5‐year overall survival, disease‐free survival, locoregional relapse‐free survival, and distant metastasis‐free survival rates were 83.2% vs. 76.2% (p = .403), 73.5% vs. 67.8% (p = .461), 90.4% vs. 86.8% (p = .551), and 82.6% vs. 79.7% (p = .632), respectively. Multivariate analysis demonstrated that CCD (240 mg/m2) was not an independent prognostic factor in either the entire cohort or stage III/IV subgroup.
Conclusion.
A CCD of ≥240 mg/m2 was not an independent prognostic factor in patients with locoregionally advanced NPC at high risk of distant metastasis, and 200 mg/m2 cisplatin may be adequate to achieve a survival benefit.
Implications for Practice:
The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin‐based concurrent chemoradiotherapy (CCRT), and the cisplatin is delivered every 3 weeks (100 mg/m2) for three cycles. However, the prognostic value of cumulative cisplatin dose (CCD) delivered during CCRT is controversial. The present study investigated the prognostic value of CCD and demonstrated that a CCD of 200 mg/m2 during CCRT is adequate to achieve satisfactory survival outcomes for patients with locoregionally advanced NPC. This finding is of great importance to clinicians because it could allow patients to avoid excessive treatment and toxicities.
摘要
背景. 本研究旨在评价顺铂累积剂量(CCD)对局部晚期鼻咽癌(NPC)患者同步放化疗(CCRT)后长期生存转归的预后价值。
方法. 在中国的7家机构开展了一项开放标签的III期多中心、随机对照临床试验, 本研究仅评估其中298例仅接受CCRT治疗的患者。比较不同CCD组的患者的生存。
结果. 298例患者的中位CCD为240 mg/m2(范围40∼320 mg/m2), 113例(37.9%)患者接受的CCD < 240(≤200)mg/m2, 而185例(62.1%)接受的CCD≥240 mg/m2。CCD≥240 mg/m2和<240 mg/m2患者的估算5年总生存率、无疾病生存率、局部无复发生存率和无远处转移生存率分别为83.2% vs. 76.2%(P=0.403)、73.5% vs. 67.8%(P=0.461)、90.4% vs. 86.8%(P=0.551)和82.6% vs. 79.7%(P=0.632)。多变量分析证实CCD(240 mg/m2)不是总队列或III/IV期亚组的独立预后因素。
结论. CCD≥240 mg/m2不是具有远处转移高风险的局部晚期NPC患者的独立预后因素, 顺铂200 mg/m2可能足以达到生存获益。The Oncologist 2016;21:1369–1376
对临床实践的提示: 目前局部晚期鼻咽癌(NPC)的标准治疗是含顺铂的同步放化疗(CCRT), 顺铂每3周给药一次(100 mg/m2), 共3周期。但CCRT治疗过程中顺铂累积剂量(CCD)的预后价值仍有争议。本研究调查了CCD的预后价值, 并证实局部晚期NPC患者的CCRT中给予CCD 200 mg/m2足以达到满意的生存转归。本研究结果对临床医生意义重大, 因为这些结果使得患者得以避免过度治疗及毒性。
This study evaluated the prognostic value of the cumulative cisplatin dose (CCD) for long‐term survival outcomes after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). A CCD of ≥240 mg/m2 was not an independent prognostic factor in patients with locoregionally advanced NPC at high risk of distant metastasis, and 200 mg/m2 cisplatin may be adequate to achieve a survival benefit.
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned ...co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.
We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 95% CI 0.34 to 0.78; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.
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