BMC Cancer 2006, 6:30 http://www.biomedcentral.com/1471-2407/6/30 cFKaiaugpsulearnse-oM4f edieartoh,veinrarlellsautirovnivatolctuhrevetys,pie.eo.fcoprnositdoecroinlg all Kaplan-Meier overall survival curves, i.e. considering all causes of death, in relation to the type of protocol. malignancies. Studies based on autopsies have verified that 40% of patients with head and neck cancers died from local relapses without evidence of distant metastases or secondary primary tumors (32%), whereas only 5% of patients died from distant metastases alone [17]. Theoretically, neoadjuvant chemotherapy can benefit a few patients directly (by tumor regression in responders), but may also reduce the incidence of distant metastases, especially in collectives with known risk factors. In a number of clinical studies of induction chemotherapy [18], neither significant downstaging nor a decreased inci- dence of distant metastases was observed. In a meta-anal- ysis, Pignon found no significant benefit from induction chemotherapy as opposed to concomitant chemotherapy in head and neck cancer [5]. In our study, local failures were the most frequent causes of death, and so far as local control is concerned we found a markedly better outcome in the CON-group. On the other hand, patients with met- achronous distant metastases were less frequent in the SEQ-group. Randomised studies comparing induction chemotherapy with subsequent radiotherapy against radiotherapy alone [2,15] have failed to showany significant advantage in terms of overall survival and disease-free survival. On the other hand, concomitant application of cytostatic drugs has resulted in significant improvement, as shown in sev- eral randomised trials, independently of fractionation [2,3,19]. Radiochemotherapy can even improve on radio- therapy alone with dose escalation [4]. In other studies, a randomised comparison between hyperfractionated dose- escalated radiotherapy and hyperfractionated radiother- apy with concomitant chemotherapy showed only slight advantages for the combined arm [20]. Only a few studies have been conducted on randomised comparisons between concomitant radiochemotherapy (with moder- ate chemotherapy dosages) and sequential radiochemo- therapy (with systemically effective chemotherapy dosages). In this regard, Adelstein [2] reported a signifi- cant increase in the local control rate using concomitant RCT. Taylor [21] achieved significantly better disease-free survival, although overall survival was not significantly increased. Conclusion In comparison with concomitant radiochemotherapy, induction chemotherapy followed by radiotherapy has lost popularity. This was confirmed by our retrospective analysis, i.e. treatment with induction chemotherapy proved inferior with regard to applicability and efficacy and resulted in unsatisfactory survival rates and low patient compliance. Although induction chemotherapy might result in higher systemic effectiveness, inferior loco- regional control dominates the clinical outcome. Schemes using simultaneous chemotherapy and hyperfractionated radiotherapy generally show greater acute toxicity and bet- ter overall survival, tumour specific survival, disease-free survival and local control if patient selection is appropri- ate. To optimise the combination of both modalities (radiotherapy and chemotherapy) the aim must be to achieve higher local effectiveness together with tolerable acute and late toxicities. Abbreviations Head-and-neck carcinoma (H&N); sequential protocol (SEQ); cisplatin (CDDP); folinic acid (FA); 5-fluorouracil (5-FU); concomitant protocol (CON); mitomycin (MMC); local control (LC); disease-specific survival (DSS); MTX (methotrexate); time-to-progression (TTP); complete remission (CR); partial remission (PR); distant metastases (DM); local failure (LF). Competing interests The author(s) declare that they have no competing inter- ests. Authors' contributions R.G. performed the radiotherapy, analysed and inter- preted the data, and drafted the tables, figures and manu- script. B. H. performed the chemotherapy and critically revised the manuscript. W. T. performed parts of the sta- tistical analysis and contributed to the figures. H. R. was the consultant for chemotherapy and established induc- tion chemotherapy plus RCT. R. F. performed the follow- up and was the consultant for diagnostics. V. B. estab- lished the concomitant RCT and was the consultant for radiotherapy. P. W. supervised the acquisition, analysis and interpretation of data, and conceived and revised the manuscript. Page 8 of 9 (page number not for citation purposes)