Homogenous dose prescription in Gamma Knife Radiotherapy: Combining the best of both worlds.

PURPOSE: Stereotactic radiosurgery with linear accelerators (LINACs) or Leksell Gamma Knife® (LGK, Elekta AB) is an established treatment option for intracranial tumors. When those are involving/abutting organs at risk (OAR), homogenous and normofractionated treatments outmatch single fraction deliveries. In such situations, it would be desirable to balance LINAC's homogeneity benefits with LGK's dose gradient attributes. In this study, we determined homogeneity and OAR sparing ranges using a non-clinical, homogenous prototype version of LGK Lightning. METHODS: We retrospectively analyzed thirty fractionated LGK Icon in-house patients with acoustic neuromas, pituitary adenomas and meningiomas. Four treatment plans were generated (54 Gy,1.8 Gy/fx) per patient: one LINAC plan, one clinical Lightning plan ("LGK") and two prototype Lightning plans ("LGK Hom" and "LGK OAR"). We analyzed Dmean and D2% for different OAR, Gradient Index (GI), Paddick Conformity Index (PCI), Homogeneity Index (HI) and beam-on-time (BOT). RESULTS: While the LINAC vs. Lightning plans (LGK Hom|LGK OAR|LGK) boast better homogeneity (median: 1.08 vs. 1.18|1.24|1.35) and shorter BOT (median: 137 s vs. 432 s|510 s|510 s), Lightning plans show improved GI (median: 6.68 vs. 3.86|3.50|3.19), similar PCI (median: 0.75 vs. 0.76|0.75|0.82) and significantly reduced OAR doses. For in-tumor OAR, LGK Hom and LINAC plans achieves similar OAR sparing with improved GI for LGK Hom. CONCLUSIONS: This study is a preliminary attempt to combine the dosimetric advantages of LINAC and LGK treatment planning. We observed that LGK plan homogeneity can be improved toward LINAC standards while maintaining the LGK advantage of favorable OAR doses and GI. Additionally, in-tumor OAR hotspots can be considerably reduced.

Targeting Treatment Resistance in Head and Neck Squamous Cell Carcinoma - Proof of Concept for CT Radiomics-Based Identification of Resistant Sub-Volumes.

PURPOSE: Radiomics has already been proposed as a prognostic biomarker in head and neck cancer (HNSCC). However, its predictive power in radiotherapy has not yet been studied. Here, we investigated a local radiomics approach to distinguish between tumor sub-volumes with different levels of radiosensitivity as a possible target for radiation dose intensification. MATERIALS AND METHODS: Of 40 patients (n=28 training and n=12 validation) with biopsy confirmed locally recurrent HNSCC, pretreatment contrast-enhanced CT images were registered with follow-up PET/CT imaging allowing identification of controlled (GTVcontrol) vs non-controlled (GTVrec) tumor sub-volumes on pretreatment imaging. A bi-regional model was built using radiomic features extracted from pretreatment CT in the GTVrec and GTVcontrol to differentiate between those regions. Additionally, concept of local radiomics was implemented to perform detection task. The original tumor volume was divided into sub-volumes with no prior information on the location of recurrence. Radiomic features from those sub-volumes were then used to detect recurrent sub-volumes using multivariable logistic regression. RESULTS: Radiomic features extracted from non-controlled regions differed significantly from those in controlled regions (training AUC = 0.79 CI 95% 0.66 - 0.91 and validation AUC = 0.88 CI 95% 0.72 - 1.00). Local radiomics analysis allowed efficient detection of non-controlled sub-volumes both in the training AUC = 0.66 (CI 95% 0.56 - 0.75) and validation cohort 0.70 (CI 95% 0.53 - 0.86), however performance of this model was inferior to bi-regional model. Both models indicated that sub-volumes characterized by higher heterogeneity were linked to tumor recurrence. CONCLUSION: Local radiomics is able to detect sub-volumes with decreased radiosensitivity, associated with location of tumor recurrence in HNSCC in the pre-treatment CT imaging. This proof of concept study, indicates that local CT radiomics can be used as predictive biomarker in radiotherapy and potential target for dose intensification.

Inverse planning in Gamma Knife radiosurgery: A comparative planning study.

PURPOSE: To determine the advantages of inverse planning using a prerelease version of Leksell Gamma Knife® (LGK) Lightning (Elekta AB, Sweden) compared to manual forward planning. METHODS: Thirty-eight patients with metastases (MET, n = 15), vestibular schwannomas (VS, n = 11) and meningiomas (MEN, n = 12), treated with LGK Icon™ at our institution, were analyzed retrospectively. For each case, an inverse (inv) and inverse full coverage (fc) treatment plan was generated using LGK Lightning and compared to the clinical plans. Several dosimetry and efficiency characteristics were compared for each indication. The mean, median difference and interquartile range were reported and the significance was assessed with a paired-sample Wilcoxon test (significance level < 0.05). Further, the inter operator variability was analyzed for multiple users. RESULTS: Inv and fc treatment plans show improved target coverage (up to 3.6%) for all analyzed paradigms. For inv plans, the selectivity is enhanced (MET: 2.9%; VS: 1.8%; MEN: 1%) and the organ at risk doses are significantly reduced (VS: up to 4.5%; MEN: up to 17.5%). For inv and fc plans, the beam on time (BOT) is shortened (MET: up to 7.9%; benign tumors: 49.5%). The inter operator variability analysis shows similar treatment plan quality with small differences in plan efficiency (difference in BOT: 1-3.3 min). CONCLUSIONS: LGK Lightning allows to generate improved LGK treatment plans regarding plan quality with reduced BOT compared to manual forward plans. The inter operator variability showed that multiple users with different experiences can generate similar treatment plan quality using LGK Lightning.