- Email: [email protected]
Reply to letter by J. Sham
217 References
1 Fu, K.K. Prognostic factors of carcinoma of the nasopharynx. Int. J. Radiat. Oncol. Biol. Phys. 6: 523-526, 1980. 2 Neel III, H. B., Taylor, W. E. and Pearson, G.R. Prognostic determinants and a new view of staging for patients with nasopharyngeal carcinoma. Ann. Otol Rhinol. Laryngol. 94: 529-537, 1985. 3 Sisson, G. A. and Pelzer, H.J. Staging system by sites: problems and refinements. Otolaryngol. Clin. North Am. 18: 397-402, 1985. 4 Sham. J. S. T., Wei, W. I. and Choy, D. Extent of nasopharyngeal carcinoma involvement inside nasopharynx: the lack of prognostic value on local control. Cancer 69: 854-859, 1992. 5 Qin, D., Hu, Y., Yah, J., Xu, G., Cai, W., Wu, X., Cao, D. and Gu, X. Analysisof 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer 61 : 1117-1124, 1988. 6 Sham, J. S. T., Choy, D. and Wei, D. Nasopharyngeal carcinoma: or-
derly neck node spread. Int. J. Radiat. Oncol. Biol. Phys. 19: 929-933, 1990. 7 Huang, S.C. Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt-60. Int. J. Radiat. Oncol. Biol. Phys. 6:401-407, 1980. 8 Sham, J. S. T. and Choy, D. Prognostic factors of nasopharyngeal carcinoma: a review of 759 patients. Br. J. Radiol. 63: 51-58, 1990. 9 Neel IIl, H. B. and Taylor, W.F. New staging system for nasopharyngeal carcinoma. Ann. Otolaryngol. Head Neck Surg. 115: 1293-1303, 1989. 10 Sham, J. S. T. and Choy, D. Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma on local control and short term survival. Head and Neck 13: 298-310, 1991. 11 Bedwinek, J. M., Perez, C. A. and Keys, D.J. Analysisof failures after definitive irradiation of epidermoid carcinoma of the nasopharynx. Cancer 45: 2725-2729. 1980.
RADION 01062 REPLY TO LETTER BY J. SHAM To the Editors,
The main concern of Dr. J. S.T. Sham is the potential impact of neoadjuvant chemotherapy on locoregional control and survival of the bulky nodal ( >~4 cm) NPC; if the chemotherapy enhances tumour control and survival, our present conclusion that Ho's N-level overrides all other nodal characteristics (including nodal size) in prognostic significance may not be valid outside the present protocol setting. Even though not published, our original analysis has shown significant association between neoadjuvant chemotherapy with both large nodal size and advanced Ho's N-level (p value being < 0.0001 in both situations). Its association with large nodal size is merely a reflection of the protocol design; its association with advanced Ho's N-level on the other hand is not at all surprising since there is a very strong correlation between advanced Ho's N-level and large nodal size (Table III). The prognostic impact (if any) of the neoadjuvant chemotherapy should affect both the bulky nodes and the advanced Ho's N-level, though possibly not to the same extent. It is rather hard to imagine that by giving neoadjuvant chemotherapy to the bulky nodes ( ~>4 cm), the prognostic significance of the nodal size has been nullified while that of the advanced Ho's N-level remains paramount and overriding. Also, our monovariate analysis (Fig. 4a, b) shows no difference in survival for nodal metastases of similar size or Ho's N-stage after using the neoadjuvant chemotherapy in 169 NPC. The impact of the chemotherapy (if any) is obviously not substantial and it should not be used as an argument to subtract from the validity of our conclusion that the Ho's nodal levels override all other nodal characteristics in prognostic significance as shown by both monovariate and multivariate analyses. In Sham and Choy's paper (Head & Neck 13: 298-310, 91), the short-term survival was governed by nodal size while the Ho's N-stage was not an independent prognostic
factor. Sham has been quite right in pointing out that the control of the nodal disease by radiotherapy is more dependent on the nodal size than the nodal level on radiobiological grounds. However, booster radiotherapy to and surgical resection of residual nodes can at least partially if not fully compensate for the loss of regional control of the bulky nodes, thus minimizing its contribution to mortality. The only exception is the huge and fixed node that remains huge and fixed after the usual radiotherapy and so not surgically salvageable. However, most of these will be Ho's N 3 anyway; it is nearly impossible to have a N l (6 cm) and very rarely a N 2 (6 cm). In another word, I don't see why a large nodal size should lead to poorer survival in their study except for its association with advanced N-stage (Ho). I am indeed most surprised to learn that the Ho's N-stage was NOT an independent prognostic factor in their paper, especially so when they are talking about early survival. As Sham himself has put it the rate of distant metastases (in addition to locoregional recurrence/ persistence) determines survival. I would like to add that distant metastasis is the main determinant of ASR in the first 2-3 years postradiotherapy, because distant metastasis tends to manifest early and kill patients sooner than the locoregional failures (without distant metastases). The Ho's N-level being so well proven to be the most significant independent factor in determining distant metastases rate (Table If, Fig. 7) just cannot suddenly lose its significance in predicting NPC survival, especially early survival. Sincerely, P. Teo (received and accepted 25 June 1992)
Department of Clinical Oncology Prince of Wales Hospital Shatin, N. T. Hong Kong
1 Fu, K.K. Prognostic factors of carcinoma of the nasopharynx. Int. J. Radiat. Oncol. Biol. Phys. 6: 523-526, 1980. 2 Neel III, H. B., Taylor, W. E. and Pearson, G.R. Prognostic determinants and a new view of staging for patients with nasopharyngeal carcinoma. Ann. Otol Rhinol. Laryngol. 94: 529-537, 1985. 3 Sisson, G. A. and Pelzer, H.J. Staging system by sites: problems and refinements. Otolaryngol. Clin. North Am. 18: 397-402, 1985. 4 Sham. J. S. T., Wei, W. I. and Choy, D. Extent of nasopharyngeal carcinoma involvement inside nasopharynx: the lack of prognostic value on local control. Cancer 69: 854-859, 1992. 5 Qin, D., Hu, Y., Yah, J., Xu, G., Cai, W., Wu, X., Cao, D. and Gu, X. Analysisof 1379 patients with nasopharyngeal carcinoma treated by radiation. Cancer 61 : 1117-1124, 1988. 6 Sham, J. S. T., Choy, D. and Wei, D. Nasopharyngeal carcinoma: or-
derly neck node spread. Int. J. Radiat. Oncol. Biol. Phys. 19: 929-933, 1990. 7 Huang, S.C. Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt-60. Int. J. Radiat. Oncol. Biol. Phys. 6:401-407, 1980. 8 Sham, J. S. T. and Choy, D. Prognostic factors of nasopharyngeal carcinoma: a review of 759 patients. Br. J. Radiol. 63: 51-58, 1990. 9 Neel IIl, H. B. and Taylor, W.F. New staging system for nasopharyngeal carcinoma. Ann. Otolaryngol. Head Neck Surg. 115: 1293-1303, 1989. 10 Sham, J. S. T. and Choy, D. Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma on local control and short term survival. Head and Neck 13: 298-310, 1991. 11 Bedwinek, J. M., Perez, C. A. and Keys, D.J. Analysisof failures after definitive irradiation of epidermoid carcinoma of the nasopharynx. Cancer 45: 2725-2729. 1980.
RADION 01062 REPLY TO LETTER BY J. SHAM To the Editors,
The main concern of Dr. J. S.T. Sham is the potential impact of neoadjuvant chemotherapy on locoregional control and survival of the bulky nodal ( >~4 cm) NPC; if the chemotherapy enhances tumour control and survival, our present conclusion that Ho's N-level overrides all other nodal characteristics (including nodal size) in prognostic significance may not be valid outside the present protocol setting. Even though not published, our original analysis has shown significant association between neoadjuvant chemotherapy with both large nodal size and advanced Ho's N-level (p value being < 0.0001 in both situations). Its association with large nodal size is merely a reflection of the protocol design; its association with advanced Ho's N-level on the other hand is not at all surprising since there is a very strong correlation between advanced Ho's N-level and large nodal size (Table III). The prognostic impact (if any) of the neoadjuvant chemotherapy should affect both the bulky nodes and the advanced Ho's N-level, though possibly not to the same extent. It is rather hard to imagine that by giving neoadjuvant chemotherapy to the bulky nodes ( ~>4 cm), the prognostic significance of the nodal size has been nullified while that of the advanced Ho's N-level remains paramount and overriding. Also, our monovariate analysis (Fig. 4a, b) shows no difference in survival for nodal metastases of similar size or Ho's N-stage after using the neoadjuvant chemotherapy in 169 NPC. The impact of the chemotherapy (if any) is obviously not substantial and it should not be used as an argument to subtract from the validity of our conclusion that the Ho's nodal levels override all other nodal characteristics in prognostic significance as shown by both monovariate and multivariate analyses. In Sham and Choy's paper (Head & Neck 13: 298-310, 91), the short-term survival was governed by nodal size while the Ho's N-stage was not an independent prognostic
factor. Sham has been quite right in pointing out that the control of the nodal disease by radiotherapy is more dependent on the nodal size than the nodal level on radiobiological grounds. However, booster radiotherapy to and surgical resection of residual nodes can at least partially if not fully compensate for the loss of regional control of the bulky nodes, thus minimizing its contribution to mortality. The only exception is the huge and fixed node that remains huge and fixed after the usual radiotherapy and so not surgically salvageable. However, most of these will be Ho's N 3 anyway; it is nearly impossible to have a N l (6 cm) and very rarely a N 2 (6 cm). In another word, I don't see why a large nodal size should lead to poorer survival in their study except for its association with advanced N-stage (Ho). I am indeed most surprised to learn that the Ho's N-stage was NOT an independent prognostic factor in their paper, especially so when they are talking about early survival. As Sham himself has put it the rate of distant metastases (in addition to locoregional recurrence/ persistence) determines survival. I would like to add that distant metastasis is the main determinant of ASR in the first 2-3 years postradiotherapy, because distant metastasis tends to manifest early and kill patients sooner than the locoregional failures (without distant metastases). The Ho's N-level being so well proven to be the most significant independent factor in determining distant metastases rate (Table If, Fig. 7) just cannot suddenly lose its significance in predicting NPC survival, especially early survival. Sincerely, P. Teo (received and accepted 25 June 1992)
Department of Clinical Oncology Prince of Wales Hospital Shatin, N. T. Hong Kong