Thank you for the opportunity to respond to the letter by Rasch et al. We are pleased they have provided additional data from a subset analysis, which sheds light on the true value of intra-arterial (IA) cisplatin chemoradiation. The subset analysis included all patients who were eligible for unilateral infusion based on the more stringent Dutch criteria, and whose primary tumor volume exceeded a total of 30 mL. It is striking to observe that local control was significantly better in the IA group compared with the intravenous group among this cohort of patients (hazard ratio [HR], 0.17; 95% confidence interval [95% CI], 0.05-0.60 [P = .0025]). Although this benefit from IA treatment was limited to the 14 of 26 patients with a large (>30 mL) tumor not extending across the midline (HR, 0.14; 95% CI, 0.03-0.72), no significant benefit was observed in the remaining 3 groups. This led Rasch et al to conclude that there is no overall difference between IA versus intravenous cisplatin chemoradiation. However, had most of the 30 patients with high-volume disease who were receiving bilateral IA infusions been treated with a unilateral approach using the less stringent North American criteria, it is our opinion that the rate of local disease control would likely have been improved. In addition, there were 29 patients in the low-volume group who received bilateral infusions and again, some of them may have benefited from a unilateral IA infusion. As we previously pointed out in the editorial1 accompanying their article,2 bilateral IA infusions are required in <5% of patients and clearly are suboptimal for local disease control. Given that 56% of patients in the IA arm received a bilateral infusion, we believe that the negative effect of the suboptimal infusions may be very real in this trial. Although patients with low tumor volume and positivity for the human papillomavirus have a better prognosis, randomized trials are still required to determine whether less intensive chemoradiation protocols are feasible for such subsets. On the contrary, if there is no apparent difference in overall toxicity between the 2 regimens, as shown in the Dutch trial, we believe that the more intensive IA cisplatin chemoradiation protocol is an option that many patients would chose.
K. Thomas Robbins MD*, Stephen B. Howell MD, * Division of Otolaryngology Head and Neck Surgery, Southern Illinois University School of Medicine, Simmons Cancer Institute at SIU, Springfield, Illinois, Department of Medicine, Moores UCSD Cancer Center, University of California at San Diego, San Diego, California.