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Journal of Clinical Oncology, Vol 23, No 12 (April 20), 2005: pp. 2864-2865 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.146
Comments on Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Mist of Mysterious ResultsDepartment of Radiation Oncology, Duke University Medical Center, Durham, NC, and Department of Radiation Oncology, Clinical Protocol Office, Koo Foundation Sun Yat-Sen Cancer Center, Pei-Tou District, Taipei, Taiwan
Department of Medicine, Duke University Medical Center, Durham, NC, and Koo Foundation Sun Yat-Sen Cancer Center, Pei-Tou District, Taipei, Taiwan To the Editor:
This is another phase III trial to evaluate the efficacy of concurrent chemotherapy and radiotherapy (CRT) followed by adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). This study enrolled patients with Ho's stage T3 or N2/3 NPC or neck node There are several pitfalls apparent in this study. First of all, the imbalance exists in patient population in the four treatment arms, American Joint Committee on Cancer (AJCC) stage II NPC now has been recognized as having better outcome than more advanced disease, and the risk of distant metastasis is low if there is no parapharyngeal space extension.2,3 Chua et al reported that the incidence of distant metastasis is 13% for all patients with parapharyngeal space extension treated with radiotherapy alone.4 This incidence would be much lower if we confine the patient group to T1-T2 diseases. Our experience says that it is less than 5%.5 In this study, the control arm (radiotherapy alone, group A) enrolled 21 patients (38.2%) with stage II NPC, which is much higher than other three arms; this potentially would offset any benefit derived from chemotherapy (CRT, AC, or both). The stage II patients in the other three groups ranged from 20.4% to 26.3%. When we look more closely at the control arm (group A) and the radiotherapy + AC arm (group C), stage II in the former is 38.2% and stage III, 47.3%; on the contrary, stage II in the latter is 20.4%, and stage III, 61.1%. Therefore, any benefit from the treatment would not overcome the weight of the poorer prognostic factors inherent in these patients. As shown in their report, the failure-free survival rate in AJCC stage II patients is 76.2%, and stage III, 63.3%. The authors also do not mention the staging methods. All patients had both computed tomography (CT) and magnetic resonance imaging (MRI) of the head and neck for locoregional tumor evaluation in their series. If discrepancy exists between two imaging modalities, how does one determine a patient's stage? Many studies have shown that MRI detects T3 and T4 disease better.6-8 Different imaging modalities could allocate patients with similar risk into different treatment groups. Lack of this consideration makes this study difficult to interpret. The locoregional failure rate in this study is too high (20% to 27.6%) to be acceptable (even for T4 disease it is only approximately 11%). By contemporary radiation treatment technique, the locoregional control rate in T1 to T3 disease should be greater than 90% and 80% in T4 disease.9-11 Kwong et al did not make an effort to properly control radiation treatment protocol. There are two different treatment regimens in this series. This may imply inattention to controlling the quality of radiotherapy even though it is the most important treatment component and a key factor of treatment success for NPC patients. Several phase III randomized trials for advanced-stage NPC have been published in recent years12-15 without being mindful of the importance of the influence of outcome due to different stage distribution of their patients, and the consensus still does not exist in the definition of "advanced-stage" NPC. The studies cited above fell into the same pitfall by enrolling NPC patients all the way from stage II to IVA-B disease (by AJCC 1997 staging system). As mentioned earlier in this letter, if a chemotherapy study protocol includes patients with low risk for distant metastasis, the benefit of chemotherapy would be either none or too small to detect. We advise that future chemotherapy trials focus mainly on stage IVA-B patients. Otherwise, these data will be self-conflicting and difficult to interpret. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Kwong DL, Sham JS, Au GK, et al: Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: A factorial study. J Clin Oncol 22:2643-2653, 2004
2. Cheng SH, Tsai SY, Yen KL, et al: Concomitant radiotherapy and chemotherapy for early-stage nasopharyngeal carcinoma. J Clin Oncol 18:2040-2045, 2000 3. Chua DT, Sham JS, Leung LH, et al: Tumor volume is not an independent prognostic factor in early-stage nasopharyngeal carcinoma treated by radiotherapy alone. Int J Radiat Oncol Biol Phys 58:1437-1444, 2004[Medline] 4. Chua DT, Sham JS, Kwong DL, et al: Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma: A significant factor in local control and distant metastasis. Cancer 78:202-210, 1996[CrossRef][Medline] 5. Cheng SH, Tsai SYC, Yen KL, et al: Prognostic significance of parapharyngeal space venous plexus and marrow involvement: Potential landmarks of dissemination for stage I-III nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 61:456-465, 2005[Medline] 6. Chung NN, Ting LL, Hsu WC, et al: Impact of magnetic resonance imaging versus CT on nasopharyngeal carcinoma: Primary tumor target delineation for radiotherapy. Head Neck 26:241-246, 2004[CrossRef][Medline] 7. Ng SH, Chang TC, Ko SF, et al: Nasopharyngeal carcinoma: MRI and CT assessment. Neuroradiology 39:741-746, 1997[CrossRef][Medline] 8. Chong VF, Fan YF: Skull base erosion in nasopharyngeal carcinoma: Detection by CT and MRI. Clin Radiol 51:625-631, 1996[CrossRef][Medline] 9. Cheng SH, Yen LKC, Jian JM, et al: Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: Impact on future clinical trials. Int J Radiat Oncol Biol Phys 50:717-726, 2001[CrossRef][Medline] 10. Lee N, Xia P, Quivey JM, et al: Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: An update of the UCSF experience. Int J Radiat Oncol Biol Phys 53:12-22, 2002[CrossRef][Medline]
11. Liu MT, Hsieh CY, Chang TH, et al: Prognostic factors affecting the outcome of nasopharyngeal carcinoma. Jpn J Clin Oncol 33:501-508, 2003
12. Lin JC, Jan JS, Hsu CY, et al: Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol 21:631-637, 2003
13. Chan AT, Teo PM, Ngan RK, et al: Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Progression-free survival analysis of a phase III randomized trial. J Clin Oncol 20:2038-2044, 2002
14. Ma J, Mai HQ, Hong MH, et al: Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma. JCO 19:1350-1357, 2001 15. Chi KH, Chang YC, Guo WY, et al: A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys 52:1238-1244, 2002[CrossRef][Medline] Related Reply
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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4 cm in a phase III factorial study.
