Seminar

Nasopharyngeal carcinoma

Patients with recurrent or metastatic NPC are left with limited treatment options. The close association between EBV and NPC make therapeutic vaccination targeting EBV-antigens an emerging new treatment modality. Therapeutic vaccination provides a stimulus to allow the patient to mount their own targeted immune response against the cancer. The two approaches that have led the field into the clinic are dendritic-cell based vaccines and virus-based vaccines. Clinical trials have shown the vaccines to be well-tolerated, and able to elicit a targeted immune response to tumor specific epitopes. Clinical efficacy data, however, is more limited given the early stage of the trials. Other approaches to developing a therapeutic vaccine for NPC include using cancer stem cell lysates, EBV-antigen peptides, and EBV-antigen plasmid DNA. Readout of ongoing trials and progression of preclinical vaccines into Phase I will shed additional light on the efficacy of vaccines and the feasibility of these different approaches to developing a therapeutic vaccine. Future studies may explore combination therapies with multiple vaccines, adoptive T-cell therapy, or checkpoint inhibitors.

: Induction Chemotherapy (IC) has the potential advantage of resulting in early eradication of micro metastasis thereby reducing distant failure in Nasopharyngeal Carcinoma (NPC). This study is to evaluate the effectiveness of induction chemotherapy in NPC based on published phase III Randomized Controlled Trials (RCT)

: We searched PubMed, SCOPUS, EMBASE and COCHRANE databases for phase III trials evaluating the role of IC in NPC using the following key words: nasopharyngeal carcinoma, locally advanced, locoregionally advanced, induction chemotherapy, and concurrent chemoradiation. We included phase 3 RCTs of NPC in which intervention patients received induction chemotherapy plus concurrent chemoradiation (CCRT) and the control patients received CCRT alone.

: Six phase III RCTs have reported the data on effectiveness of IC in NPC so far. All except one study found statistically significant improvement in the primary outcome. One study demonstrated improved relapse free survival (RFS) with IC (stratified HR for recurrence or death 0.51; p=0.0001). Two studies reported improvement in disease free survival (DFS) with IC [adjusted HR 0.739 (p=0.0264) in one study; HR for 3-year and stratified HR for 5-year DFS 0.67 (p=0.028) and 0.66 (p=007) respectively in the other study]. One study demonstrated improvement in failure free survival (FFS) with IC [HR for 3-year and 5-year FFS 0.68 (p=0.034) and 0.67 (p=0.019) respectively] and another study reported improved progression free survival (PFS) [HR 0.44; p=0.042)]. Grade 3-4 acute adverse events were higher among patients who received IC.

: IC followed by CCRT showed superior clinical outcomes in NPC compared to CCRT alone. Conflicting results were found with regard to overall survival.

The aim of this study was to investigate the influence of CD4⁺, CD8⁺ and Forkhead box protein 3 (FoxP3⁺) tumor-infiltrating lymphocytes, as well as CD1a⁺ tumor-infiltrating dendritic cells on the radiosensitivity and survival of primarily chemoirradiated advanced head and neck squamous cell carcinomas.

Immunohistochemical staining for CD4, CD8, FoxP3 and CD1a was performed in 82 primarily chemoirradiated head and neck squamous cell carcinomas. Associations with clinicopathologic data, programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), p16, radiation response, and survival were examined.

High CD4 expression was associated with complete response after radiation (P = .006) and high CD1a expression (P = .024). High CD8⁺ tumor-infiltrating lymphocyte counts were associated with absence of tumor relapse (P = .032) and better disease-free survival (P = .051). Strong overall T-cell infiltration was found more often in tumors with high-grade differentiation (P = .004), complete response after radiation (P = .022), and better overall survival and disease-specific survival (each P = .052). Tumors with high FoxP3⁺ T regulatory (T_reg) infiltration more often showed high-grade tumor differentiation (P = .017), advanced patient age (P = .02), high PD-1 (P = .007), high CD4 (P = .002), and high CD8 expression (P = .002), as well as better disease-free survival (P = .019).

T-cell activation (high CD4, CD8 and FoxP3 expression) is associated with radio response and favorable survival in advanced head and neck cancer treated with definitive chemoradiation.

In nasopharyngeal carcinoma (NPC), the staging category of parotid lymph node (PLN) metastasis is not explicitly defined, resulting in varied classifications and treatment strategies in clinical practice. This study aimed to determine the prognostic value and optimal staging category of PLN metastasis in NPC.

With the NPC database from a big-data platform, 10,126 patients with primarily diagnosed, non-metastatic NPC and treated with intensity modulated radiotherapy at our center from 2009 to 2015 were analyzed in this study.

In total, 43/10126 patients (0.4%) were diagnosed with histologically verified PLN metastasis at initial diagnosis. Of these, 88.4% (38/43) had enlarged lymph nodes in level II and 34.9% (15/43) in level Ib. Compared with patients without PLN metastasis, those with PLN metastasis had higher risk of disease failure (adjusted hazard ratio [HR], 1.770), distant metastasis (HR, 1.907), and regional recurrence (HR, 3.649), with similar 3-year disease-free survival (70.0% vs. 71.1%) and distant metastasis-free survival (74.8% vs. 77.4%) with patients with N3 disease. Of note, 10/43 patients had regional recurrence: six had recurrent lymph nodes in level Ib; and four of these six patients had no identifiable level Ib lymph nodes on pretreatment imaging.

PLN metastasis was associated with high risk of distant metastasis and regional recurrence, and patients with PLN metastasis had similar outcome compared with patients with N3 disease. Regional recurrences in rare levels, such as level Ib, were common in patients with PLN metastasis at initial diagnosis.