Original article Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy Damien C. Weber a,b,c,⇑ , Robert Malyapa a , Francesca Albertini a , Alessandra Bolsi a , Ulrike Kliebsch a , Marc Walser a , Alessia Pica a , Christophe Combescure d , Antony J. Lomax a,e , Ralf Schneider a a Center for Proton Therapy, Paul Scherrer Institute; b University of Bern; c University of Zürich; d Unité d’Epidemiologie Clinique, Hôpitaux Universitaire de Genève; and e ETH, Zürich, Switzerland article info Article history: Received 3 February 2016 Received in revised form 26 April 2016 Accepted 16 May 2016 Available online xxxx Keywords: Skull base tumors Chordoma Chondrosarcoma Pencil beam scanning Proton therapy abstract Purpose: To evaluate the long term tumor control and toxicity of skull base tumors treated with pencil beam scanning proton therapy (PT). Materials and methods: PT was delivered to 151 (68%) and 71 (32%) chordoma and chondrosarcoma (ChSa) patients, respectively. Mean age of patients was 40.8 ± 18.4 years and the male to female ratio was 0.53. The postoperative tumor was abutting the brainstem or optic apparatus in 71 (32.0%) patients. The postoperative mean gross tumor volume (GTV) was 35.7 ± 29.1 cm 3 . The delivered mean PT dose was 72.5 ± 2.2 Gy RBE. Results: After a mean follow-up of 50 (range, 4–176) months, 35 local (15.8%) failures were observed between 10.9 and 85.4 months. The estimated 7-year LC rate for chordoma (70.9%; CI95% 61.5–81.8) was significantly lower compared to the LC rate for ChSa patients (93.6%; 95%CI 87.8–99.9; P = 0.014). The estimated 7-year distant metastasis-free- and overall survival rate was 91.6% (95%CI 91.6–98.6) and 81.7% (95%CI 74.7–89.5), respectively. On multivariate analysis, optic apparatus and/or brainstem compression, histology and GTV were independent prognostic factors for LC and OS. The 7-year high grade toxicity-free survival was 87.2 (95%CI 82.4–92.3). Conclusions: PBS PT is an effective treatment for skull base tumors with acceptable late toxicity. Optic apparatus and/or brainstem compression, histology and GTV allow independent prediction of the risk of local failure and death in skull base tumor patients. Ó 2016 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2016) xxx–xxx Chordoma arises from remnants of the embryonal notochord, located usually at the superior and lower aspect of the axial skele- ton. This rare tumor, with an incidence of approximately 0.8–1 per million [1] and accounting for approximately 1–4% of all bone tumors [2], is characterized by its locally aggressive growth and a propensity for local recurrences. As a result of the close proximity of critical structures, the surgical management of these tumors is challenging and maximally safe resection with postoperative high-dose radiation therapy is usually recommended. Likewise, chondrosarcoma (ChSa) of the skull of base is an even rarer bone tumor [3,4] that arises from the chondrocytes or their precursor cells involved in the endochondral ossification, most commonly in the petroclival junction. These tumors are also managed with cytoreductive surgery and with postoperative radiotherapy in most cases [5]. Particle beam therapy including but not limited to proton ther- apy (PT) and carbon ion therapy, is usually administered to these challenging patients because these radiation modalities can deliver high-dose radiation, while sparing organs at risk (OARs) in direct vicinity of the target volume. The advantages of PT, which is usu- ally delivered with a passive scattering paradigm, are their finite range in tissue, lower integral patient-dose and zero exit dose. Pro- tons can be magnetically deflected and scanned within the tumor, allowing an optimization of the proximal dose deposition when compared to passive scattered protons [6]. Pencil beam scanning (PBS) PT has been pioneered by the Paul Scherrer Institute (PSI) since the 1990s [7] and over 1100 patients have been safely treated with PBS. We have evaluated the outcome of skull base patients with chordoma and ChSa treated with PBS PT and have assessed the major prognostic factors for these two locally invasive tumors. http://dx.doi.org/10.1016/j.radonc.2016.05.011 0167-8140/Ó 2016 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: Center for Proton Therapy, Paul Scherrer Institute, WPTA 144, CH-5232 Villigen West, Switzerland. E-mail addresses: damiencharles.weber@uzh.ch, damien.weber@psi.ch (D.C. Webe. Radiotherapy and Oncology xxx (2016) xxx–xxx Contents lists available at ScienceDirect Radiotherapy and Oncology journal homepage: www.thegreenjournal.com Please cite this article in press as: Weber DC et al. Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy. Radiother Oncol (2016), http://dx.doi.org/10.1016/j.radonc.2016.05.011