Response In Nasopharyngeal Carcinoma Research Articles

Radiological, pathological and DNA remission in recurrent metastatic nasopharyngeal carcinoma

BackgroundCirculating plasma Epstein Barr Virus DNA (EBV-DNA) is a sensitive and specific marker of nasopharyngeal carcinoma (NPC). The mainstay of treatment of metastatic NPC is systemic chemotherapy and resection for solitary metastasis. Despite high response rate to chemotherapy, complete remission is uncommonly seen.Case PresentationWe report a case of recurrent metastatic NPC in a 43-year-old man, who achieved complete remission three times with chemotherapy and surgery. Serial plasma EBV-DNA levels were measured during the course of disease. The patient had three episodes of recurrences of NPC manifested as distant metastasis. Both time, rise in the plasma EBV-DNA level preceded detection of recurrences by imaging. Following systemic chemotherapy, he achieved complete remission each time, of which was confirmed by 18-flourodeoxyglucose positron emission tomography and hepatectomy pathology. The plasma EBV-DNA level dropped to zero copy/ml at the time of each remission.ConclusionThis case highlights the high chemosensitivity of NPC by illustrating a rare occurrence of complete response of metastatic NPC to chemotherapy. This case also underscores the usefulness of EBV-DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response.

O.128 Oral squamous cell carcinoma, histologic risk assessment

To evaluate the feasibility of utilizing serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) prospectively for early prediction of neoadjuvant chemotherapy (NAC) response in nasopharyngeal carcinoma (NPC) patients.Sixty-three advanced NPC patients were recruited and received three DCE-MRI exams before treatment (Pre-Tx), 3 days (Day3-Tx) and 20 days (Day20-Tx) after initiation of chemotherapy (one NAC cycle). Early response to NAC was determined based on the third MRI scan and classified partial response (PR) as responders and stable disease (SD) as non-responders. After intensity-modulated radiotherapy (IMRT), complete response (CR) patients were classified as responders. The kinetic parameters (Ktrans, Kep, ve, and vp) derived from extended Tofts' model analysis and their corresponding changes ΔMetrics(0–X) (X = 3 or 20 days) were compared between the responders and non-responders using the Student's T-test or Mann–Whitney U test.Compared to the SD group, the PR group after one NAC cycle presented significantly higher mean Ktrans values at baseline (P = 0.011) and larger ΔKtrans(0–3) and ΔKep(0–3) values (P = 0.003 and 0.031). For the above parameters, we gained acceptable sensitivity (range: 66.8–75.0%) and specificity (range: 60.0–66.7%) to distinguish the non-responders from the responders and their corresponding diagnosis efficacy (range: 0.703–0.767). The PR group patients after one NAC cycle showed persistent inhibition of tumor perfusion by NAC as explored by DCE-MRI parameters comparing to the SD group (P < 0.05) and presented a higher cure ratio after IMRT than those who did not (83.3% vs. 73.8%).This primarily DCE-MRI based study showed that the early changes of the kinetic parameters during therapy were potential imaging markers to predicting response right after one NAC cycle for NPC patients.

O.126 Dynamic MRI for assessment of mandibular invasion in oral SCC

To evaluate the feasibility of utilizing serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) prospectively for early prediction of neoadjuvant chemotherapy (NAC) response in nasopharyngeal carcinoma (NPC) patients.Sixty-three advanced NPC patients were recruited and received three DCE-MRI exams before treatment (Pre-Tx), 3 days (Day3-Tx) and 20 days (Day20-Tx) after initiation of chemotherapy (one NAC cycle). Early response to NAC was determined based on the third MRI scan and classified partial response (PR) as responders and stable disease (SD) as non-responders. After intensity-modulated radiotherapy (IMRT), complete response (CR) patients were classified as responders. The kinetic parameters (Ktrans, Kep, ve, and vp) derived from extended Tofts' model analysis and their corresponding changes ΔMetrics(0–X) (X = 3 or 20 days) were compared between the responders and non-responders using the Student's T-test or Mann–Whitney U test.Compared to the SD group, the PR group after one NAC cycle presented significantly higher mean Ktrans values at baseline (P = 0.011) and larger ΔKtrans(0–3) and ΔKep(0–3) values (P = 0.003 and 0.031). For the above parameters, we gained acceptable sensitivity (range: 66.8–75.0%) and specificity (range: 60.0–66.7%) to distinguish the non-responders from the responders and their corresponding diagnosis efficacy (range: 0.703–0.767). The PR group patients after one NAC cycle showed persistent inhibition of tumor perfusion by NAC as explored by DCE-MRI parameters comparing to the SD group (P < 0.05) and presented a higher cure ratio after IMRT than those who did not (83.3% vs. 73.8%).This primarily DCE-MRI based study showed that the early changes of the kinetic parameters during therapy were potential imaging markers to predicting response right after one NAC cycle for NPC patients.

1079 PUBLICATION Role of CT imaging in predicting response of nasopharyngeal carcinoma to definitive radiation therapy

1079 PUBLICATION Role of CT imaging in predicting response of nasopharyngeal carcinoma to definitive radiation therapy

Serum Responses to the Combination of Epstein-Barr Virus Antigens in Patients With Nasopharyngeal Carcinoma in a Follow-up Study

Background. Elevated serum IgA to Epstein-Barr virus (EBV) antigens was frequently found in patients with nasopharyngeal carcinoma (NPC). Recent evidence indicated that EBV in NPC patients could be a mixture of latent and active infections. Methods. In this longitudinal study, we therefore used six EBV antigens from both latent and acute phases of infection to evaluate NPC patients. Immunosensitivity was determined using enzyme-linked immunosorbent assay, and immunospecificity was assessed using immunoblot. Results. Levels of serum IgA to EBV in NPC patients were significantly higher than the levels in the healthy control subjects. Persistent high IgA titer or the aberrant increase of IgA level indicated a high risk of disease recurrence and early distant metastasis. Conclusions. Disease progression of NPC was proceeded by the increase of IgA titer to EBV antigens. Measurement of serum IgA to a panel of EBV antigens from both latent and acute viral . infections could, therefore, provide a predictive index for NPC response.

Beta 2-microglobulin and HLA-DR expression in relation to the presence of Epstein-Barr virus in nasopharyngeal carcinomas.

We have investigated the immunohistochemical expression of beta 2-microglobulin and HLA-DR proteins in nasopharyngeal carcinoma (NPC) in relation to the expression of the Epstein-Barr virus (EBV)-encoded EBER 1-2 mRNAs and LMP-1 protein. beta 2-Microglobulin is expressed in association with MHC-I molecules on most nucleated cells and HLA-DR belongs to the MHC-II molecules which are expressed mostly on antigen-presenting cells. Formalin-fixed paraffin-embedded tissue from 37 NPC cases was stained with immunohistochemistry for beta 2-microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for EBER 1-2 mRNAs. beta 2-Microglobulin-positive staining was found in neoplastic cells in all cases. In 19/37 NPC cases the positive staining was found in most neoplastic cells. In the remaining 18 NPC cases more than 25% of the neoplastic cells showed significantly reduced or negative staining in comparison to the normal epithelium and infiltrating small lymphocytes. HLA-DR-positive staining was found in 27/37 NPC cases. EBER 1-2 transcripts were deteced in neoplastic cells in 13/37 NPC cases. LMP-1 expression in tumour cells was found in 4/13 EBER1-2-positive cases. No correlation was found between the presence of EBER1-2 transcripts or LMP-1 protein and the beta 2-microglobulin-reduced expression in NPC. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T cell cytotoxic immune response in NPC. HLA-DR expression was observed in all 13 EBV-positive cases of NPC, suggesting that EBV may participate in the induction of HLA-DR expression in a proportion of NPC.

A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma.

The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.

Activated T lymphocytes in infiltrates and draining lymph nodes of nasopharyngeal carcinoma

Lymphocytes isolated from the tumors and draining lymph nodes of nasopharyngeal carcinoma (NPC) patients exhibit the following characteristics of immune activation: (1) stable E rosette formation, (2) natural attachment to various human cells, (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the NPC T cells attach in vitro to various cells they kill only EBV-genome-carrying targets. These findings suggest the occurrence of a local cellular immune response in NPC, possibly directed to EBV-determined antigens.

Epstein‐barr virus‐specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma

Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV-induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV-specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2-6 years after initial therapy had only low levels of EBV-specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA-specific IgA and even fewer EA-specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA- or D-specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV-specific antibodies. Possible reasons for this unique response in NPC have been discussed.