Nasopharyngeal Carcinoma: A Retrospective Review of 26 Patients

Auris' Nasus' Larynx (Tokyo) 19 (Supp!. I) S 119-S 125, 1992

NASOPHARYNGEAL CARCINOMA: A RETROSPECTIVE REVIEW OF 26 PATIENTS Hiromi VEDA, M.D., Masakatsu TAKAHASHI, MD., Hayato TSUGE, M.D., and Noriyuki YANAGITA, M.D. Department of Otorhinolaryngology. Nagoya University School of Medicine. Nagoya. Japan

We analyzed retrospectively the data on 26 patients with nasopharyngeal carcinoma who were treated at our university school of medicine between 1982-1988. Twelve patients received radiotherapy alone; 8 received chemotherapy prior to the radiotherapy, and 6 received chemotherapy following the radiotherapy. The overall 5-year survival rate was 64.8%. In all but one patient with adenocarcinoma, the survival rates were significantly higher in those with stages I-III than with stage IV disease. The patients with cervical metastasis had a poorer prognosis as compared with those without cervical metastasis. The incidence of distant metastasis increased with the advance of N stage, but there was no correlation between T stage and primary recurrence. Malignant tumors of the nasopharynx are relatively uncommon in Japan; and the incidence rate is approximately 0.19 per 100,000 per year as calculated from Sawaki's report, I comparable with that reported in caucasians/ but only 2 fraction (0.01) of that reported in Hong Kong. 3 Because of the difficulty in making an early diagnosis and the inaccessibility of the tumor to surgery, the results of treatment are rather poor. Recent advances in diagnostic technology including computerized tomography, as well as in technique of radiation therapy may help to improve our control of both the primary lesion and the cervical metastasis. In this report, we present the results and prognostic factors identified in a retrospective analysis of 26 such patients treated at our university. MATERIALS AND METHODS

Twenty-six patients with nasopharyngeal carcinoma ,(NPC) were treated at Received for publication September 1, 1992 Presented at the 7th Asia-Oceania Congress of Otorhinolaryngological Societies, Hong Kong. December 2-5, 1991. S119

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the Department of Otorhinolaryngology of the Nagoya University School of Medicine between January 1982 and December 1988. The study comprised 19 males and 7 females (Fig. 1). Their ages ranged from 19 to 74 years. The most common initial signs/symptoms and findings on admission were loss of hearing or ear obstruction (13 cases), and the presence of a mass in the neck (8 cases). Other signs included bleeding from the nose (3 cases), and diplopia (1 case). All 26 cases were categorized retrospectively according to the TNM clinical classification in 1987 recommended by the International Union Against Cancer. 4 Table 1 shows the TNM system and staging. As compared with the previous classification,S the T and M staging were the same as in 1987, but the staging of N2 and N3 differs slightly. Table 2 shows the staging of our servey patients classified according to this system. No patients had stage I disease, while those with stages II and III des eases were 5 and 3, respectively. In this study, 18 of 26 patients (69%) had stage IV disease, but only a few had T3 and/or N3. The cases were histologically documented as lymphoepithelioma (14), squamous cell carcinoma (10), transitional cell carcinoma (1), and adenocarcinoma (1). All patients received radical irradiation with cobalt 60 photon beams. Commonly, the first dosage period involved radiation with large opposing anteriorposterior portals include the nasopharynx and whole neck enbloc. When a dose of 20 Gy had been reached, the primary lesion was treated through opposing lateral portals. At the same time the lymph nodes of the neck were irradiated through an anterior portal with a midline spinal cord block to a dose of 40 Gy. The total dose of radiation administered was approximately 60 Gy. Additional irradiation (electrons from a betatron directed to neck lymph nodes or linear accelarator to the primary lesion) was employed as necessary. Chemotherapy was administered before radiation to 8 patients, and after radiation to 5 patients. Those administered chemotherapy had advanced disease or residual tumor following irradiation. Survival curves were estimated by the Kaplan-Meier method. 6 Comparison of 5-year survival rates was done by using the Z-test to evaluate the difference between standard errors of survival.

NASOPHARYNGEAL CARCINOMA Table I.

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TNM clinical classification recommended by UICC (1987).

T-Primary tumor Tx Primary tumor cannot be assessed TO No evidence of primary tumor Tis Carcinoma in situ TI Tumor limited to one subsite of nasopharynx T2 Tumor invades more than one subsite of nasopharynx Tumor invades nasal cavity and/or oropharynx T3 T4 Tumor invades skull and/or cranial nerve(s) N---Regional lymph nodes Nx Regional lymph nodes cannot be assessed NO No regional lymph node metastasis NI Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6cm in greatest dimension N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6cm in greatest dimension N3 Metastasis in a lymph node more than 6cm in greatest dimension Note: Midline nodes are considered ipsilateral nodes. M-Distant metastasis Mx Presence of distant metastasis cannot be assessed MO No distant metastasis MI Distant metastasis Stage grouping NO MO Stage 0 Tis Stage I Tl NO MO Stage II NO MO T2 Stage III NO MO T3 NI MO Tl T2 NI MO NI MO T3 Stage IV NO, NI MO T4 MO N2, N3 Any T Any T Any N MI

RESULTS

Survival Survival curves appear in Fig. 2. The 5-year overall survival rate was 64.8%; the 5-year disease-free survival rate was 51.5%. Because lymphoepithelioma or transitional cell carcinoma are variants of undifferentiated squamous cell carcinoma, we assessed some 25 patients with lymphoepithelioma, transitional cell carcino-

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TNM classification (DICC, 1987). T2

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Fig. 2. Overall and disease-free survival curves for 26 patients with nasopharyngeal carcinoma. A solid and dotted line indicated the overall survival and disease-free survival curves, respectively.

rna, and squamous cell carcinoma. The 5-year survival rate was 100% for stages JIII and 55.1% for stage IV (Fig. 3). The patients with stages I-III disease had a significantly (p < 0.01) better prognosis than those with stage IV disease. Figure 4 (upper diagram) indicates the survival curves by T staging. Patients with Tl T2 stages appeared to have a better prognosis, although there was no significant difference in the 5-year survival rate between the patients with primary lesions ofTlT2 vs those with T3T4. The lower diagram in Fig. 4 demonstrates the survival curves by N stage. The 5-year survival rate for the patients with and without cervical metastasis was 100 and 56.4%, respectively. Patients with cervical metastasis had a significantly (p < 0.01) poorer prognosis as compared to those without cervical metastasis.

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Recurrence Fourteen of the 26 patients did not develop recurrent disease. One patients with adenocarcinoma had residual carcinoma in the primary area, even after the initial treatment. The other 11 patients developed recurrences at intervals ranging from 1 to 5 years. The location of recurrence in descending order was the primary area (5 cases), the liver (3 cases), and bone (1 case). We could not determine the the site of recurrence in 2 patients who died of recurrent disease, as we were informed of their death only by a letter from the family. The patients who developed distant metastasis after the initial treatment were those with an initially

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advanced initial N stage. The patients who developed a primary recurrence included 2 with T4 disease and 2 with T2 disease. DISCUSSION

The five-year disease-free survival of patients with nasopharyngeal carcinoma reported by other institutes ranged from 30 to 50%.2.7. 8 At our university, the 5year disease-free survival was 51.5%, relatively high as compared with the abovementioned reports. We treated 26 such cases, a relatively small number as compared with other reports. In addition, patients with T3 and/or N3 stage was rare in our study. The factors may account for the higher rate of survival. However we stage T and N in all patients by computed tomography (CT), in addition to physical examination. Yamashita et al reported that examination by CT improved the period of survival free of local recurrence, and the period of survival free of cervical relapse, because they obtained precise information about tumor invasion. 9 Such examination may also help to improve the 5-year survival rate. Our observations indicate that disease stage had a major effect on prognosis. Some investigators similarly reported that the survival rates decreased with an increase in disease stage. 2.10 There is a controversy concerning the correlation of prognosis and T staging. Dickson and Flores found no significant difference in survival rates between patients with Tl, T2, and T3 lesions, with only the T4 stage showing a dramatic reduction in survival. 2 However, Cellai et al concluded that there was no significant difference in survival among T stages, except for T 1. II Baker and Wolfe reported finding no correlation between the extent of the primary tumor (T) and survival. 12 Bentzen et al indicated that crude survival versus the T classification showed a significant trend in the Danish, but not in the Inuit, population. 1O Hoppe et al reported that local control decreased with an increase in T stage. 13 In our series, patients with T 1T2 stages had a better prognosis than those with T3T4 stages, but they showed no significant difference in 5-year survival. Many reports have found a good correlation between the N stage and survival rate,2.11.12 with only Bentzen et al reporting that a comparison of N stage revealed no significant difference in survival. 10 In our small series, the 5-year survival of patients with cervical metastasis significantly exceeded that of patients without this complication. . In conclusion, our findings indicate that the presence of neck node involvement provides better prognostic information than does the extent of primary tumor in nasopharyngeal carcinoma. REFERENCES I.

Sawaki S: Basic and clinical research of nasopharyngeal carcinoma. J Otolaryngol Jpn 82:13451351. 1979.

NASOPHARYNGEAL CARCINOMA 2. 3. 4. 5. 6. 7. 8. 9. 10.

II. 12. 13.

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Dickson RI, Flores AD: Nasopharyngeal carcinoma: An evaluation of 134 patients treated between 1971-1980. Laryngoscope 95:276-283,1985. Lau WH: Nasopharyngeal carcinoma (NPC): Epidemiology and treatment. Head Neck Cancer Jpn 13:10-14, 1986. Union Internationale Contre Ie Cancer: TNM Classification of Malignant Tumors (4th ed), UICC, Geneva, 1987. Union Internationale Contre Ie Cancer: TNM Classification of Malignant Tumors (3rd ed), UICC, Geneva, 1978. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-481, 1958. Amornmarn R, Prempree T, Sewchand W, et al: Radiation management of advanced nasopharyngeal cancer. Cancer 52:802-807, 1983. Chu AM, Flynn MB, Achino E, et al: Irradiation of nasopharyngeal carcinoma: Correlations with treatment factors and stage. Int J Radiat Oncol BioI Phys 10:2241-2249, 1984. Yamashita S, Kondo M, Inuyama y, et al: Improved survival of patients with nasopharyngeal squamous cell carcinoma. Int J Radiat Oncol BioI Phys 12:307-312, 1986. Bentzen JKD, Ockelmann HH, Albeck H, et al: Nasopharyngeal carcinoma treated at the Finsen Institute, Copenhagen 1965-1985: Survival and some prognostic factors. Laryngoscope 10 I :635642, 1991. Cellai E, Chiavacci A, Olmi P, et al: Carcinoma of the nasopharynx. Results of radiation therapy. Acta Radiol Oncol 21 :87-94, 1982. Baker Sr, Wolfe RA: Prognostic factors of nasopharyngeal malignancy. Cancer 49: 163-169, 1982. Hoppe RT, Goffinet DR, Bagshaw MA: Carcinoma of the nasopharynx: 18 years' experience with megavoltage radiation therapy. Cancer 37:2065-2612, 1976.

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Dr. H. Ueda, Department of Otorhinolaryngology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan