Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients based on plasma Epstein–Barr virus DNA level after induction chemotherapy

Abstract

Purpose: This study aimed to elucidate the optimal cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) according to the post-induction chemotherapy (IC) plasma Epstein-Barr virus (EBV) DNA level. Results: EBV DNA was detected and undetected in 179 and 370 patients, respectively. Of the entire cohort, 73/549 (13.3%) patients received a total CCD ≥ 160 mg/m 2 and 476/549 (86.7%) patients, <160 mg/m 2. CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, higher 3-year PFS and locoregional relapse-free survival (LRFS) rates were observed in those who received a CCD ≥ 160 mg/m 2. Multivariate analysis also showed CCD was an independent prognostic factor for PFS and LRFS in patients with post-IC detectable EBV DNA. Conclusions: CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, those receiving ≥160 mg/m 2 CCD showed significantly improved 3-year PFS and LRFS. Methods: NPC patients (549) treated with IC and CCRT were included. Prognosis was assessed using a multivariate Cox proportional hazards model. Furthermore, grade 1-4 toxicities were compared between different CCD groups.

Nomograms for predicting survival outcomes in intensity‐modulated radiotherapy era of nasopharyngeal carcinoma: A study based on Epstein–Barr virus DNA biological responses

“…This is in good agreement with previous studies 13,15 . Notably, the percentage of patients (75.8%) with detectable post‐IC EBV DNA in this research was much higher than previous studies (23.7%–36.8%) 16 . These differences can be explained by the large interlaboratory variability.…”

“…Furthermore, the nomograms were successfully applied for risk stratification of NPC patients. Therefore, it is possible to guide clinicians to conduct personalized therapy in clinical practice, including early treatment modification for high‐risk patients, which implies that they should receive therapeutic intensification, such as targeted therapy and immunotherapy 16 17 . Although the rapid resolution of circulating tumor DNA was proved to be an effective prognosticator in many tumor types, it still requires more prospective clinical trials for validation in the future as well as HPV positive oropharyngeal cancers 34 …”

“…Recently, post‐IC EBV DNA has been proved to be a more powerful and earlier outcome predictor than post‐chemoradiotherapy EBV DNA 15 . Patients with detectable post‐IC EBV DNA could benefit from high cumulative cisplatin dose (≥ 160 mg/m 2 ) while those with undetected post‐IC EBV‐DNA failed 16 . Therefore, it is reasonable to integrate EBV DNA biological responses with treatment regimes for survival prediction 17 …”

Prognostic model for risk stratification of de novo metastatic nasopharyngeal carcinoma patients treated with chemotherapy followed by locoregional radiotherapy

“…Previous studies showed that the CCD of CCRT after IC was not an independent prognostic factor for OS. 20 , 21 , 22 , 23 , 24 However, a dose of CCD ≥200 mg/m 2 had the trend to prolong OS benefit in those with an unfavorable response to IC. In our study, we did not observe a statistically significant difference in OS between de novo mNPC patients treated with radiotherapy alone versus concomitant chemoradiotherapy after first-line chemotherapy.…”

Establishment of a Prognostic Nomogram for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Incorporating TNM Stage, Post-Induction Chemotherapy Tumor Volume and Epstein-Barr Virus DNA Load

“…Wen et al demonstrated that high-risk patients with advanced T or N stage, higher pre-DNA or larger post-IC tumor volume benefited from CCD ≥ 200 mg/m 2 for PFS and DMFS (37). A previous study also showed that patients with detectable post-DNA showed significantly improved 3-year PFS and LRFS by receiving ≥ 160 mg/m 2 CCD (38). [2] Add targeted therapy to the treatment regimen.…”