No abstract

Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.

This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.

Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.nasopharyngeal carcinoma | somatic mutation landscape | NF-κB signaling | whole-exome sequencing | APOBEC-mediated signature

No abstract

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.

Similar longitudinal age-specific incidence rates along with converging IRRs indicate that the age effects for invasive breast cancer are more similar among Asian and Western populations than might be expected from a solely cross-sectional analysis. Indeed, the Asian breast cancer rates in recent generations are even surpassing the historically high rates in the United States, highlighting an urgent need for efficient prevention and treatment strategies among Asian populations.