Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients

  • Olgun ElicinEmail author
  • Burim Sermaxhaj
  • Beat Bojaxhiu
  • Mohamed Shelan
  • Roland Giger
  • Daniel Rauch
  • Daniel M. Aebersold
Original Article



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).


The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively 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 patients 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.


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.


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.


Squamous cell carcinoma Radiation Anti-epidermal growth factor receptor Cisplatin Carboplatin Secondary malignancies 



Epidermal growth factor receptor


Head and neck squamous cell carcinoma


Human papillomavirus


Overall survival


Second primary cancer


Union for International Cancer Control

Inzidenz von metachronen Zweitkarzinomen nach Strahlentherapie in Kombination mit Platin und/oder Cetuximab bei Patienten mit Kopf-Hals-Tumoren



Über die Inzidenz von metachronen Zweitkarzinomen („second primary cancer“, SPC) nach platinbasierter Chemotherapie und Cetuximab in Kombination mit einer Radiotherapie ist bisher nichts bekannt. Ziel war es, das SPC-Risiko bei Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereichs (HNSCC) nach durchgeführter kombinierter Radiotherapie mit den genannten Substanzen zu evaluieren.


Zwischen 2009 und 2015 wurden 296 Patienten aufgrund eines lokoregionär fortgeschrittenen HNSCC behandelt und bezüglich patienten-, tumor- und therapieassoziierten Charakteristika retrospektiv analysiert. Alle Patienten wurden entweder für eine Radiotherapie mit platinbasierter Chemotherapie (Platin-Gruppe) oder Antikörpertherapie mit Cetuximab (Cetuximab-Gruppe) eingeplant. Die dritte Gruppe bestand aus Patienten, die aufgrund einer Platinunverträglichkeit einen Substanzwechsel auf Cetuximab vollzogen (Switch-Gruppe). Die Inzidenz des SPC wurde mit dem Log-rank-Test errechnet. Mögliche Confounder wurden durch das multivariate Cox-Regressionsmodell (Cox’s proportional hazards model) detektiert. Alle Tests erfolgten zweiseitig; ein p-Wert <0,05 galt als statistisch signifikant.


Die mediane Nachbeobachtungszeit betrug 36 Monate. In der Platin-Gruppe waren 158, in der Cetuximab-Gruppe 101 und in der Switch-Gruppe 37 Patienten. Die 3‑Jahres-Gesamtüberlebensrate der gesamten Kohorte war 70%. Die SPC-Raten waren zwischen der Platin- (9,2 %) und Cetuximab-Gruppe (11,5 %) vergleichbar (p = 0,98). In der Switch-Gruppe ließ sich hingegen nach 3 Jahren eine signifikant höhere Inzidenz (p = 0,01) von SPC (23,3 %) nachweisen. Im multivariaten Modell korrelierte ein Substanzwechsel als einzige Variable mit einem erhöhten SPC-Risiko.


Der Substanzwechsel von einer platinbasierten Substanz auf Cetuximab könnte für Patienten ein erhöhtes Risiko für eine SPC-Entwicklung darstellen. Ein Substanzwechsel sollte aufgrund fehlender, robuster präklinischer und klinischer Daten vorsichtig ausgeübt werden.


Plattenepithelkarzinom Radiotherapie Anti-epidermal growth factor receptor Cisplatin Carboplatin Systemische Therapie 



We thank Dr. Emanuel Stutz for his valuable input to the manuscript.

Authors’ contributions

Conception and design of the study: OE; data acquisition and quality control of data: BS, BB, MS, OE; statistical analysis: OE; manuscript preparation, editing, review and approval: all co-authors.

Compliance with ethical guidelines

Conflict of interest

O. Elicin received honoraria for his consulting role in the advisory boards of AstraZeneca, Merck, and Merck Serono. B. Sermaxhaj, B. Bojaxhiu, M. Shelan, R. Giger, D. Rauch, and D.M. Aebersold declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Radiation Oncology, Inselspital, Bern University HospitalUniversity of BernBernSwitzerland
  2. 2.Department of Otorhinolaryngology, Head and Neck Surgery, InselspitalBern University HospitalBernSwitzerland
  3. 3.Department of Medical Oncology, Inselspital, Bern University HospitalUniversity of BernBernSwitzerland

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