Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer.

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). RESULTS: Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001). CONCLUSIONS: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.

Can Epstein-Barr virus-deoxyribonucleic acid load after induction chemotherapy combined with American Joint Committee on Cancer stage determine the chemotherapy intensity of locally advanced nasopharyngeal carcinoma?

BACKGROUND: Induction chemotherapy (IC) comprising docetaxel, cisplatin, and fluorouracil (TPF), combined with concurrent chemoradiotherapy (CCRT) effectively improves the survival rate of locally advanced nasopharyngeal carcinoma (LA-NPC). Selecting patients whose risk of tumor recurrence and metastasis is high and the appropriate chemotherapy intensity is a concern. We combined tumor-node-metastasis staging with the load of Epstein-Barr virus (EBV) after IC to select the individualized chemotherapy strength. METHODS: The clinical data and prognostic factors of patients with stage III-IV LA-NPC treated with TPF IC combined with CCRT were analyzed retrospectively. The conventional treatment group received the standard three cycles TPF IC combined with CCRT. For the new treatment group, the cycles of IC were determined according to whether the EBV-DNA disappeared completely after a certain course of IC, if so, subsequent IC was stopped and the chemoradiotherapy stage was entered. Propensity score matching (PSM) was performed at a ratio of 1:1 to balance baseline characteristics. Survival outcomes and adverse events between the conventional treatment group and the new method treatment group were compared. RESULTS: The study included 256 patients, among whom 192 were matched successfully into 96 pairs. The patients were followed up for a median of 51 months. The proportions of patients receiving three, two, and one cycle of IC after PSM in the routine and new treatment cohorts were 93.8%, 3.1%, 3.1% versus 21.9%, 49.0%, 24.0%, respectively. However, their 3-year distant metastasis-free survival, local recurrence-free survival, progression-free survival, and overall survival did not differ significantly. The incidence of grade 3-4 neutropenia toxicity in CCRT decreased significantly in patients receiving the new treatment method compared with that in the conventional treatment group (p = 0.026). CONCLUSION: Combining TNM stage and EBV-DNA load after IC to determine the courses of IC in patients with LA-NPC did not alter the curative effect but decreased toxicity.

Explore the Usefulness of Concurrent Chemotherapy in Stage II Nasopharyngeal Carcinoma: A Retrospective Study.

Objective: This study aims to compare the treatment outcomes of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in stage II nasopharyngeal carcinoma (NPC) patients. Methods: We retrospectively collected 601 stage II NPC patients treated in two hospitals between June 2003 to June 2016. All patients were divided into the CCRT group (n = 255) and the RT group (n = 346). Overall survival (OS), locoregional failure-free survival (LRFFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. The log-rank test was used to compare the differences between the groups. The Cox-regression hazards model was performed to determine potential prognostic factors. Results: The median follow-up was 99 months. No significant difference was found in locoregional recurrence, distant metastasis, disease progression, and death between the two groups (all p > 0.05). In univariate analysis, the 5-years OS, PFS, LRFFS, and DMFS had no significant differences between the CCRT and RT groups (all p > 0.05). Two-dimensional radiotherapy (2DRT) sub-analysis showed that CCRT remarkably increased DMFS, PFS, and OS rates (all p < 0.05) but not LRFFS (p = 0.258) compared with RT alone. While intensity-modulated radiotherapy (IMRT) sub-analysis showed that the prognosis of the two groups had no significant differences (all p > 0.05). In multivariate analyses, age was significantly and inversely related to OS, PFS, LRFFS, and DMFS. IMRT was an independent favorable factor for improving LRFFS, PFS, and OS. Concurrent chemotherapy was an independent protective factor for DMFS. Conclusion: In the context of 2DRT, it is definite that concurrent chemotherapy provides survival benefits for patients with stage II NPC. While in the IMRT era, the impact of chemotherapy on survival in patients with stage II NPC is weakened. Prospective randomized controlled studies are required to confirm these results.