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Abstract Background Skull base chordomas are rare and heterogeneously behaving tumors. Though still classified as benign they can grow rapidly, are locally aggressive, and have the potential to metastasize. To adapt the treatment to the specific needs of patients at higher risk of recurrence, a pre-proton therapy prognostic grading system would be useful. The aim of this retrospective analysis is to assess prognostic factors and the “Sekhar Grading System for Cranial Chordomas” (SGSCC) by evaluating the larger cohort of patients treated at our institution as to determine its reproducibility and ultimately to ensure more risk adapted local treatments for these challenging tumors. Methods We analyzed 142 patients treated for skull base chordomas between 2004 and 2016. We focused the analysis on the 5 criteria proposed for the SGSCC (tumor size, number of anatomic regions and vessels involved, intradural invasion, as well as recurrence after prior treatment) and classified our patients according to their score (based on the above mentioned criteria) into three prognostic groups, low-risk, intermediate-risk and high-risk. The three groups were then analyzed in regards of local control, local recurrence-free survival and overall survival. Results The median follow up was 52 months (range, 3–152). We observed 34 (24%) patients with a local recurrence, resulting in a local control of 75% at 5 years. Overall survival was 83% at 5 years, 12 (9%) patients had died due to local progression. When split into the three prognostic groups according to the SGSCC the observed local control was 90, 72 and 64% (p = 0.07) in the low-, intermediate- and high-risk group, respectively. A similar correlation was observed for local recurrence-free survival with 93, 89 and 66% (p = 0.05) and for overall survival with 89, 83 and 76% (p = 0.65) for the same prognostic groups. Conclusions After splitting our patient cohort into the three SGSCC risk groups, we found a trend towards better outcome for those patients with lower as opposed to higher scores. These results suggest that this prognostic grading system published by Sekhar et al. could be integrated in the management decision-tree for patients with skull base chordoma.

Background: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. Results: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (−35.2%, −32.7%; −35.2%, −33.0%, respectively), cerebellum (−53.7%, −33.1%; −53.6%, −32.7%) and right temporal lobe (−14.5%, −31.9%; −14.7%, −29.9%). The Willis’ circle was better protected with PBS-PT than IMRT (−7.1%; −7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. Conclusions: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT’s superiority over VMAT, thus potentially minimizing long-term sequelae. Keywords: Pediatric germ cell tumor, Pencil beam scanned proton therapy, Intensity-modulated radiation therapy, Volumetric-modulated arc therapy, Dose comparison study, Neurocognition brain structures

For pencil beam scanned (PBS) proton therapy, analytical dose calculation engines are still typically used for the optimisation process, and often for the final evaluation of the plan. Recently however, the suitability of analytical calculations for planning PBS treatments has been questioned. Conceptually, the two main approaches for these analytical dose calculations are the ray-casting (RC) and the pencil-beam (PB) method. In this study, we compare dose distributions and dosimetric indices, calculated on both the clinical dose calculation grid and as a function of dose grid resolution, to Monte Carlo (MC) calculations. The analysis is done using a comprehensive set of clinical plans which represent a wide choice of treatment sites. When analysing dose difference histograms for relative treatment plans, pencil beam calculations with double grid resolution perform best, with on average 97.7%/91.9% (RC), 97.9%/92.7% (RC, double grid resolution), 97.6%/91.0% (PB) and 98.6%/94.0% (PB, double grid resolution) of voxels agreeing within  ±5%/±  3% between the analytical and the MC calculations. Even though these point-to-point dose comparison shows differences between analytical and MC calculations, for all algorithms, clinically relevant dosimetric indices agree within  ±4% for the PTV and within  ±5% for critical organs. While the clinical agreement depends on the treatment site, there is no substantial difference of indices between the different algorithms. The pencil-beam approach however comes at a higher computational cost than the ray-casting calculation. In conclusion, we would recommend using the ray-casting algorithm for fast dose optimization and subsequently combine it with one MC calculation to scale the absolute dose and assure the quality of the treatment plan. [ABSTRACT FROM AUTHOR]