The review by Mendenhall et al presents selected papers pertinent to the effect of metastatic nodes on local control in patients with head and neck cancer. These data are retrospective and, as the authors point out, do not resolve the matter.
Two Studies Not Included in the Review
The authors do not include a paper by Griffin et al in their review . These researchers analyzed 997 patients with primary head and neck cancer who were entered into the Radiation Therapy Oncology Group (RTOG) head and neck cancer registry and were treated by radiotherapy alone. Pertinent data, such as tumor site, T stage, and N stage, were all prospectively recorded.
Griffin et al found that T stage, N stage, primary site, and initial Karnofsky performance score were significant independent predictors of primary tumor response. They designed a multivariate response model using these factors to predict primary tumor response, the predictive accuracy of which was very impressive. It was tested by comparing predicted and observed tumor clearance rates (O/P ratio) for each independent variable. For the 996 patients evaluated, the ratios according to N stage were: N0, 1.01; N1, 0.93; N2, 1.03; and N3, 1.01.
In contrast to this is a very fine paper from Spain by Cerezo et al , who analyzed 492 squamous cell carcinomas of the head and neck with positive nodes. The paper focused on failure in patients with clinically positive nodes and the identification of prognostic factors for survival and control. The authors failed to show an effect on primary tumor control except in N3 disease, for which control was better than in N2 or N1 disease in a multivariate analysis. Cerezo et al suggest that this observation may be due to N3 disease being more frequent in nasopharyngeal carcinoma. Elsewhere, they comment on the problems posed by retrospective studies.
How the Problem May Be Elucidated
A final paper by Johnson et al , which was included in the review by Mendenhall et al, used an elegant method of quantitative tumor volume measurements from CT scans that indicated how this problem may be elucidated. They estimated the tumor volume (TV) and nodal volume (NV) and combined these as the total tumor volume (TTV) estimate. They were able to show that TTV was the most important outcome predictor of local control. The separate effects of TV and NV could not be discerned in this study (51 cases) but, obviously, could help resolve the controversy. Certainly, these tumor volume measurements help overcome the imprecision of clinical staging.
Are We Losing Sight of the Forest for the Trees?
In conclusion, I am left with the feeling that we are losing sight of the forest for the trees. Our problem with radiotherapy, as pointed out by Cerezo et al, is recurrence at the primary site (20%), and N stage, particularly fixed nodes, is a major prognostic factor for survival in head and neck cancer. The study by Johnson et al demonstrates the importance of TTV. With these points in mind, I believe that more aggressive treatment, whatever the modality employed, would be justified in patients meeting these criteria, but obviously should be given in the setting of a clinical trial.