ORIGINAL ARTICLE https://doi.org/10.1007/s00066-018-1400-5 Strahlenther Onkol Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients Olgun Elicin 1 · Burim Sermaxhaj 1 · Beat Bojaxhiu 1 · Mohamed Shelan 1 · Roland Giger 2 · Daniel Rauch 3 · Daniel M. Aebersold 1 Received: 6 July 2018 / Accepted: 8 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Purpose The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC). Methods The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospec- tively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of pa- tients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox’s proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance. Results Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC. Conclusions The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available. Keywords Squamous cell carcinoma · Radiation · Anti-epidermal growth factor receptor · Cisplatin · Carboplatin · Secondary malignancies Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.  Olgun Elicin, M.D. olgun.elicin@insel.ch Burim Sermaxhaj, M.D. burim.sermaxhaj@insel.ch Beat Bojaxhiu, M.D. beat.bojaxhiu@psi.ch Mohamed Shelan, M.D. mohamed.shelan@insel.ch PD Roland Giger, M.D. roland.giger@insel.ch Daniel Rauch, M.D. daniel.rauch@insel.ch Prof. Daniel M. Aebersold, M.D. daniel.aebersold@insel.ch 1 Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 4, 3010 Bern, Switzerland 2 Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, Bern University Hospital, Freiburgstrasse, 3010 Bern, Switzerland 3 Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, 3010 Bern, Switzerland K