Tsong-Chou Lynn

Nasopharyngeal cancer: Study III. A review of 1206 patients treated with combined modalities

A combination of radiation therapy and chemotherapy was used in an attempt to improve the control of nasopharyngeal cancer (NPC). From 1979 through 1983, 1206 patients with histologically proven NPC were treated with routine radiation along with 5 combinations of drug or drugs in small to maintenance doses. The drugs used were: 1) cyclophosphamide p.o. (CTX), 2) methotrexate p.o. (MTX), 3) CTX + MTX, 4) bleomycin i.v. (BLM), and 5) cisplatin + BLM i.v. (BP). The actuarial survival rates and recurrence rates were chosen as endpoints for comparison to previous studies. The overall survival rate increased from 43.5% in study I, and 56% in study II to 70.6% in the present study. The recurrence rate declined to 13%, but was less impressive. The encouraging results were more obvious in groups of patients with bilateral large cervical lymph nodes, reaching statistical significance (p less than 0.01).

Pathology of nasopharyngeal carcinoma. Proposal of a new histologic classification correlated with prognosis

To establish a new histologic classification with better correlation with patient prognosis, the histologic features of nasopharyngeal carcinoma (NPC) were correlated with prognosis and clinical stage among 494 patients who had been followed a minimum of 5 years after initial radiotherapy. A slight modification of World Health Organization (WHO) classification by the separation of spindle cell variant from the nonkeratinizing (NK) and undifferentiated carcinomas (UD) provided a better prognostic correlation: keratinizing squamous cell carcinoma (KS), spindle cell carcinoma (SP), round cell carcinoma (RC), and mixed cell carcinoma (Mix, or NK); 5‐year survival rates were 21%, 41%, 51.8%, and 54% respectively. This prognostic distinction was further improved by dividing the three nonkeratinizing carcinomas (SP, RC, and Mix) into two subtypes each, according to the degree of cell anaplasia and pleomorphism: Type A (with marked anaplasia and/or pleomorphism), and Type B (with moderate or little anaplasia). The three Type A carcinomas had very similar 5‐year survival rates (33.3 to 38.6%), as did the three Type B carcinomas (60% to 71.8%). Therefore, a working formulation for the malignancy of NPC emerged: (1) high‐grade malignancy (KS; 5‐year survival, 21%), (2) intermediate malignancy (Type A carcinomas, 5‐year survival, 30%–40%), and (3) low‐grade malignancy (Type B carcinomas, 5‐year survival rate, 60%–72%). The prognostic distinction remained true after stratification by clinical stage. Therefore, the histologic condition of the tumor of NPC correlated with patients prognosis. Cancer 59:945‐951, 1987.

Serum glycoproteins and immunoglobulins in nasopharyngeal carcinoma: correlations with Epstein-Barr virus associated antibodies and clinical tumor stage.

The consistent association of elevated antibody titers to the Epstein-Barr virus associated antigens in patients with nasopharyngeal carcinoma has led to correlations of antibody titers with tumor presence and extent. Recently, serum levels of specific glycoproteins and immunoglobulins have been correlated with tumor presence and extent in patients with head and neck squamous carcinomas, and elevation of the immunoglobulin IgA has been described in patients with nasopharyngeal carcinoma. These correlations prompted a study of 69 untreated patients with nasopharyngeal carcinoma and 53 healthy normal subjects in Taiwan to determine the relations among specific proteins (haptoglobin, α1-acid glycoprotein, α1-antitrypsin, α2-HS-glycoprotein, prealbumin, and albumin), immunoglobulin levels (IgA, IgG, IgM), anti-EBV associated antibody titers, and clinical tumor stage. Elevated antibody titers to EBV-associated antigens (EBV-associated nuclear antigen, viral capsid antigen, and early antigen) were related to tumor presence but not significantly related to clinical tumor stage. Compared with the levels in normal subjects, serum levels of acute-phase proteins (haptoglobin, α1-acid glycoprotein, α1-antitrypsin) were significantly increased (p < 0.001) in patients with nasopharyngeal carcinoma, and levels of α2HS-glycoprotein were significantly decreased (p < 0.001). Uniquely, serum levels of acute-phase proteins, particularly haptoglobin, were directly related to clinical tumor stage (p < 0.05 − 0.001). Furthermore, serum haptoglobin levels correlated directly with anti-EBNA antibody titers (p < 0.03) and serum levels of IgA (p < 0.01). Serum levels of α2HS-glycoprotein correlated inversely with titers of IgA antibodies to early antigen (p < 0.03). The findings demonstrate that measurement of specific serum glycoprotein and immunoglobulin levels may be useful adjuncts to anti-EBV antibody titers in the serodiagnosis and monitoring of response to treatment of nasopharyngeal carcinoma and aid in the derivation of improved staging systems for these tumors.

Long-term follow-up of IgG and IgA antibodies against viral capsid antigens of Epstein-Barr virus in nasopharyngeal carcinoma

A total of 137 patients with biopsy-proved anaplastic epidermoid nasopharyngeal carcinoma (NPC) seen at the National Taiwan University Hospital from December 1971 through December 1973, were studied serologically before radiotherapy and during the follow-up period up to December 1982. A clear control study on 134 healthy patients or patients with diseases other than NPC was also done. EB virus-associated anti-VCA antibodies in both IgG and IgA classes were titrated by means of indirect immunofluorescent antibody method on two to six samples of serum from the patients during the follow-up study. When seropositive standard was set at 1:640 for anti-VCA/IgG and 1:40 for anti-VCA/IgA, the seropositive rates were 63.5 per cent and 81.1 per cent for NPC patients before treatment and 2.9 per cent and 2.2 per cent for the control respectively. The differences of seropositive rates between the patients and control were statistically highly significant, as chi 2 greater than 111, p less than 0.0005. At the completion of radiotherapy and during the following year, some reduction and fluctuation of seropositive rates were seen in both cured and recurrent patients. From the second year after radiotherapy and thereafter, the seropositive rates were 72 per cent-100 per cent for patients with recurrences and 17.6 per cent-30.8 per cent for cured patients. The differences were significant (chi 2 greater than 24.8, p less than 0.0005). Therefore, high titres of anti-VCA antibodies may coexist with cancer tissue in NPC patients. IgA class antibodies is slightly higher in sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Epstein-barr virus-associated antibodies and serum biochemistry in nasopharyngeal carcinoma†‡

Nasopharyngeal carcinoma is difficult to diagnose in its early stages. It also has frequent recurrences and/or distant metnstases after radiotherapy. Extensive clinical, serological and biochemical studies were done during 1980‐1982 on 351 patients to aid in the diagnosis of the disease, especially with recurrence or metastasis.

Immunologic Reactivity in Patients with Nasopharyngeal Carcinoma

Immunologic reactivity was measured in 344 patients with nasopharyngeal carcinoma (NPC), before treatment, and in 398 age-matched control subjects. The data recorded suggest that depressed cell-mediated immunity in patients with NPC is a consequence rather than a cause of the disease. In order to reduce tumor burden in patients with NPC, radiation therapy with chemotherapy or immunopotentiation or both is recommended.

Epstein--Barr virus-associated antibodies in IgG and IgA of nasopharyngeal carcinoma patients.

Sera from 126 patients with nasopharyngeal carcinoma (NPC), 48 other cancers (OC) and 54 normal controls (NC) were collected at the National Taiwan University Hospital and tested for immunoglobulin levels as well as for IgG and IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA), early antigen (EA) and nuclear antigen (EBNA) by the immunofluorescence antibody technique. The mean concentrations of IgA and IgG in untreated NPC patients were higher than those of OC and NC groups, but IgM level was lower than that of OC group. The incidence and geometric mean titers (GMT) of anti-EA and anti-VCA in serum IgG and IgA, and anti-EBNA were substantially higher in NPC patients than in OC and NC groups. The GMT of anti-VCA in IgG and IgA, and anti-EA in IgG increased with advancing clinical stages of NPC but no such an increment was observed in anti-EBNA. After successful treatment the GMT of anti-VCA in IgG and IgA, anti-EA in IgG, and anti-EBNA became lower than those of pre-treatment and these antibody titers except anti-EBNA titers increased again in recurrent cases, indicating that tests for EBV-associated antibody titers are useful for monitoring the clinical status of NPC. In untreated and treated NPC patients, anti-VCA in IgG and IgA were significantly correlated (correlation coefficient r = 0.65 and 0.72 respectively, i.e. p < 0.005 in both groups). A correlation was also observed in anti-EA in IgG and IgA in untreated NPC patients (r = 0.2, p < 0.05). Among 11 throat washings of untreated NPC patients tested, anti-EA and anti-VCA in both IgG and IgA were detected in 1, 5, 1 and 2 cases, respectively.

EBV-Associated Antibodies and Other Antibodies in Nasopharyngeal Cancer Patients before and after Radiotherapy

Patients with nasopharyngeal carcinoma(NPC) have, in general, elevated antibody titers against EBV-associated antigens(1–3). These antibody titers are decreased in general after radiation therapy(4,5). On the other hand, antibodies against H. simplex virus(HSV) and H. zoster virus (HZV) in NPC patients may be normal(6–8) or increased(9). The present communication revealed that the decrease of EBV-associated antibodies after radiation therapy was a unique and specific phenomenon in NPC patients.

Dynamics of Epstein--Barr virus antibody titre in nasopharyngeal carcinoma.

Abstract Eighty-three sera from 20 regressor patients and 53 sera from 12 progressor patients with nasopharyngeal carcinoma (NPC) were studied for IgG antibodies against viral capsid antigens of Epstein-Barr virus. The regressors were found to have their antibody titres decreased during and/or after radiotherapy, and stayed at low titres thereafter. On the contrary, in the progressor, although the antibody titres decreased transiently sometime during and/or after radiotherapy, most patients returned to high titres soon. The implication of this phenomenon is discussed, and adjuvant therapy to NPC patients is suggested.