BMC Cancer 2006, 6:30 http://www.biomedcentral.com/1471-2407/6/30 tFKuiamgpuloarrne--rMe3leaiteerdddiseeaatshes-,sipnerceifliactisounrvtiovatlhceutryvpees, oi.fe.pcrotnoscidoelring Kaplan-Meier disease-specific survival curves, i.e. considering tumor-related deaths, in relation to the type of protocol. With regard to disease-specific survival, a multivariate analysis of the significant prognostic factors from the uni- variate analysis revealed T-stage (≤ T3 vs. T4, p < 0.001), N-stage (≤ N2a vs. N2b, N3, p < 0.001), performance sta- tus (p = 0.04) and treatment protocol (SEQ vs. CON, p < 0.01) as significant predictors. The total dose showed bor- derline significant correlation (p = 0.06) with disease-spe- cific survival, whereas there was no significant correlation for the RTOG stage. N-stage (p = 0.00), treatment protocol (p = 0.03) and radiation dose (p = 0.05) proved signifi- cant for overall survival. Discussion Radiochemotherapy is becoming increasingly established as a standard method for treating inoperable head and neck carcinomas, but the optimal scheme is still under discussion. One reason is the large variation in risk factors among patient groups. It has been found that the percentage of local control after 5 years following a treatment regimen consisting solely of radiotherapy is improved by adding chemotherapy (5-FU, cisplatin etc.), which has conferred survival benefit in a number of trials. Several studies have failed to demon- strate any influence on the frequency of systemic dissemi- nation. We evaluated two different radiochemotherapeutic approaches to patients with locally advanced head and neck cancer. Prognostic factors were more or less equally distributed in the two groups. Clearly, the groups differed in treatment parameters in concerning radiation dose, cytotoxic drugs, treatment time, etc. Therefore, it might be difficult to estimate the influence of a single parameter on treatment outcome. In our study, improvements in dis- ease staging and support measures could not have been major contributors. Treatment technique, treatment plan- ning and radiation therapy technology were not changed significantly in our institution during the time encom- passing the studies on the two groups. In general, our results suggest that concomitant radioche- motherapy is superior with respect to local control, but not unequivocally with respect to distant metastases or overall survival. The regenerative response of clonogens may weaken the contribution of induction chemotherapy to locoregional control. In addition, the toxicity of the applied dose-intense chemotherapy often impaired the regular administration of radiotherapy within the SEQ- group (an attribute of the sequential scheme), resulting in treatment interruptions that led to a mean treatment time twice as long as in the CON-group. This shows that the impairment in quality of life following sequential treat- ment – in addition to worse results – may be greater than the adverse effects of concomitant radiochemotherapy. The 5-year overall survival rates (15% vs. 24%) and 5-year disease-free survival rates (20% vs. 31%) are relatively low in both groups, obviously because all except one patient suffered from stage IV disease, and a high proportion of patients in both groups had unfavourable prognostic indica- tors (see table 1). Other investigators report similarly low overall survival rates for patients with comparably unfa- vourable prognostic factors [4,12,13]. Better treatment results are achieved with selected collec- tives. Regarding recent prospective trials, 3-year local con- trol rates of 50–70% are not uncommon in patients treated with irradiation and concurrent chemotherapy (with conventional or altered fractionation) [14]. For example, Dinges et al. [10] reported a high disease-free survival rate of 59% and a local control rate of 72% after 4 years using the treatment schedule applied in the CON- group of our analysis. Overall, most of the published stud- ies [14] report 2–3 year overall survival rates of around 20–30% following radiotherapy and 40–50% following concomitant radiochemotherapy [3,14-16], comparable to our 30–40% 2-3-year survival rate after concomitant RCT (fig. 5). The difference of about 10% can easily be explained by the poor prognostic indicators of our (rather unselected) patient groups. Note that in a large meta-anal- ysis with more than 10,000 patients, the survival rates for any kind of locoregional treatment plus chemotherapy (including radical surgery with adjuvant or neoadjuvant chemotherapy) were not higher than 36% after 5 years [5], compared to 24% in our CON group. Patients with unresectable head and neck tumors have a limited risk of death from distant metastases, at least in comparison to patients suffering from gastrointestinal Page 7 of 9 (page number not for citation purposes)