The etiology, natural history, and options of therapy of nasopharyngeal cancer are unique among the mucosal cancers arising in the head and neck region. In addition, the tumor occurs only rarely in typical North American populations and most reported American series contain relatively few patients. In this issue of the Journal, two American groups contribute to our knowledge of this disease: One report is more noteworthy for the size of the reported population, and the other for its application of cutting-edge technology. Sanguineti et al. ( 1) report a retrospective analysis of 378 patients treated for nasopharyngeal cancer at the M. D. Anderson Cancer Center by radiotherapy alone between the years 1954 and 1992. Although three-fourths of the patients had far-advanced disease that would be considered AJCC Stage IV (according to the rules of the 4th edition of the AJCC manual, 1992), the 5-year actuarial survival rate for the entire group was a respectable 48% and the local control rate 71%. Moreover, these results were achieved over a 38-year time span, during which time methods of detection and therapy improved substantially. For example, computed tomography and magnetic resonance imaging scanning, for more accurate delineation of the extent of disease, and electron beam irradiation of posterior cervical lymph nodes did not exist in 1954. Thus, it would seem fair to assume that the results of radiation therapy alone in a more exclusively contemporary series might be even better. One way in which radiation therapy might be more effective is described in the report by Cmelak et al. (2) from Stanford University. They describe the use of linac-based stereotactic radiosurgery in the treatment of 59 malignant lesions that involved the base of the skull including 11 previously untreated nasopharyngeal carcinomas (four T2, two T3, and five T4-sized). After doses of 64.8-70 Gy, these 11 patients received stereotactic boosts of 716 Gy, and with a median follow-up of 18 months, 100% of the tumors were controlled within the boost volume (one patient developed a local recurrence outside of the boost volume, adjacent to the jugular foramen). Certainly, a dose-response relationship can be inferred, raising the hope that a substantial improvement over the already respectable local control rates reported by the M. D. Anderson group are now achievable with conformal techniques and greater doses. Yet, it must be asked if either of these reports are relevant to nonexperimental patient care in 1997. The recently completed Intergroup No. 0099 study (3) tested the value of simultaneously delivering cisplatin chemotherapy with standard radiation therapy followed by maintenance cisplatin and 5-fluorouracil chemotherapy. In a prospective randomized comparison, multimodality therapy significantly improved survival (80% at 2 years) compared to radiation therapy alone (55% at 2 years). In fact, multimodality therapy was so far superior that the trial was stopped earlier than originally planned. Local control, regional control, and distant control of disease were all significantly improved by the addition of chemotherapy. Thus, it seems appropriate to ask if the Intergroup No. 0099 data are sufficient to conclude that treatment of advanced, nondisseminated nasopharyngeal cancer by radiation therapy alone no longer represents the standard of care. Although I would be more confident if confirmatory data were available, I believe that the answer is yes. However, we should not conclude that we have a final answer. We simply do not have enough data to know if the long-term local control rates of high-dose conformal radiation therapy are equal to, better than, or worse than those produced by chemotherapy-enhanced conventional radiation therapy. This is particularly relevant for the T4NOMO Stage IV cancers that were included in the Intergroup trial, since the predominant mode of treatment failure for these tumors is local recurrence. Perhaps conformal boosts can be combined with chemotherapy-enhanced conventional radiation therapy to produce even more frequent or more durable local control than can chemotherapy-enhanced conventional radiation therapy. On the other hand, severe toxicity may preclude this option. Certainly, this is a potential lead for future investigations.
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Jay S. Cooper (1997) studied this question.