CUHK oncologists propose risk-based treatment algorithm for locally advanced nasopharyngeal carcinoma
Researchers from the Chinese University of Hong Kong (CUHK) have used emerging clinical data to formulate a risk-based treatment algorithm for locally advanced nasopharyngeal carcinoma (NPC), focusing on optimal integration of induction, concurrent, and/or adjuvant chemotherapy with intensity-modulated radiotherapy (IMRT), and risk stratification based on detectable plasma Epstein-Barr virus (EBV) DNA.
The researchers have performed a recursive partitioning analysis (RPA) of the largest prospective circulating cell-free plasma EBV DNA screening cohort (n=745) in NPC to date and developed a risk model integrating post-RT plasma EBV DNA and tumour-lymph node-metastasis (TNM) staging to stratify NPC patients for adjuvant therapy. [Curr Opin Oncol 2020;32:187‐195]
The RPA classified NPC patients into low-, intermediate-, and high-risk groups with 5-year overall survival (OS) rates of 89.4 percent, 78.5 percent, and 37.2 percent, respectively. The RPA risk model was further validated in two independent internal (n=340) and external (n=837) validation cohorts.
“Our RPA risk group demonstrated better hazard discrimination over TNM stage or post-RT EBV DNA alone, with improved calibration and consistency in all primary and secondary survival outcomes. Moreover, the RPA low-risk group shared the same excellent 5-year OS as TNM stage II patients, yet identified more than twice the number of NPC patients who could be potentially spared from the toxicity of adjuvant therapy,” reported the researchers. [Ann Oncol 2019; 30:ix97-ix106]
“In Hong Kong, plasma EBV DNA assay is readily available from several companies at an affordable cost of USD 50–100,” the researchers noted.
Induction chemotherapy for locally advanced NPC downsizes the tumour, facilitating subsequent RT planning. Induction chemotherapy followed by chemoradiotherapy (CRT) was listed as a category 1 option in the National Comprehensive Cancer Network (NCCN) 2019 guidelines for NPC. [NCCN Clinical Practice Guideline in Oncology, Head and Neck Cancers, Version 1.2020] “However, the key to successful induction chemotherapy is to select an effective regimen that can be delivered in full dose without toxicities that would delay or compromise subsequent full-course CRT,” wrote the researchers.
Most recently, a parallel-group, multicentre, randomized, controlled, phase III trial of 480 patients with locally advanced NPC (stage III–IVB excluding N0 disease) from Guangzhou has shown that gemcitabine-cisplatin induction plus concurrent CRT improve both recurrence-free survival (hazard ratio [HR], 0.51; 95 percent confidence interval [CI], 0.34 to 0.77) and OS (HR, 0.43; 95 percent CI, 0.24 to 0.77) vs concurrent CRT alone. [N Engl J Med 2019;381:1124-1135]
“As the OS of locally advanced NPC continues to improve, long-term treatment-related toxicity intensified by CRT and quality-of-life issues have become important concerns,” wrote the researchers. The only phase III trial to date that compared CRT with RT alone for stage II NPC demonstrated significantly improved survival at the cost of more acute toxicity, leading to the current guideline recommendation of CRT for stage II NPC. [J Natl Cancer Inst 2011;103:1761-1770]
“Since IMRT became the standard [form of RT], several retrospective analyses have suggested that IMRT alone may achieve the same survival outcome as CRT and may be considered an option for the low-risk group … [while] for high-risk group [eg, as defined by plasma EBV DNA >4,000 copies/mL], the addition of chemotherapy should remain the standard,” postulated the researchers. [J Clin Oncol 2006;24:5414-5418]