Background: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/ cm), intermediate-frequency (100-300 kHz) alternating electric-fields. More recently interference of TTFields with DNAdamage-repair and synergistic effects with radiotherapy were reported in the preclinical setting. This study aims at examining the dosimetric consequences of TTFields applied during the course of radiochemotherapy. Methods: Cone-beam-computed-tomography (CBCT)-data from the first seven patients of the PriCoTTF-phase-I-trial were used in a predefined way for dosimetric verification and dose-accumulation of the non-coplanar-intensitymodulated-radiotherapy (IMRT)-treatment-plans as well as geometric analysis of the transducer-arrays by which TTFields are applied throughout the course of treatment. Transducer-array-position and contours were obtained from the low-dose CBCT's routinely made for image-guidance. Material-composition of the electrodes was determined and a respective Hounsfield-unit was assigned to the electrodes. After 6D-fusion with the planning-CT, the dose-distribution was recalculated using a Boltzmann-equation-solver (Acuros XB) and a Monte-Carlo-dose-calculation-engine.
PurposeThe aim of the present study based on the PriCoTTF‐phase I/II trial is the quantification of skin‐normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin‐sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined.Material and MethodsLow‐dose cone‐beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF‐phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation‐to‐fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose‐volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot‐spots of 0.05 cm2 and 25 cm2 (D0.05cm2, D25cm2) size in the superficial skin layers were analyzed.ResultsNormal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin‐NTCP by a factor of 5.50 (95%, CI: 3.66–8.27). The variation of array positioning increased skin‐NTCP by a factor of only 3.54 (95%, CI: 2.36–5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm2 over all patients and scenarios (rs = 0.76; P < 0.0001).ConclusionSkin‐NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high‐ and low‐risk groups of skin toxicity. Array position variation may mitigate about one‐third of the increase in surface dose and skin‐NTCP by the TTField electrodes.
Purpose/ObjectivesTo perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases.Methods/MaterialsDiagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities.ResultsEight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm3 (SD, 650.82), and the mean GTV volume was 12.23 cm3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5–4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V9.1 showed significantly smaller volumes with IORT [63.39 cm3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D90 was 85.3% (SD, 6.05), whereas D95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively.ConclusionKilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis.
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