Lung stereotactic radiation therapy: Intercomparison of irradiation devices in terms of outcome and predictive factors.

To compare three different radiotherapy devices able to perform pulmonary stereotactic radiotherapy: CyberKnife® (CK), Helical Tomotherapy® (HT), and volumetric modulated arc therapy (VMAT). This study aims to define the patients' outcome in terms of SBRT efficacy and toxicities depending of the device choice. We retrospectively analyzed the clinical, radiological, and dosimetric data of patients treated with lung SBRT between 2016 and 2020 at Lausanne University Hospital, using the Chi <sup>2</sup> test for proportions, the t-test for means comparisons, the Kaplan-Meier method for survival, and the Log-rank test and Cox-regression for intergroups comparisons. We identified 111 patients treated by either CK (59.9%), VMAT (38.0%), or HT (2.1%). Compared to other techniques, CK treated comparable gross tumor volume (GTV; 2.1 vs. 1.4cm <sup>3</sup> , P=0.84) with smaller planning treatment volume (PTV; 12.3 vs. 21.9cm <sup>3</sup> , P=0.013) and lower V5 (13.5 vs. 19.9cm <sup>3</sup> , P=0.002). Local control rates at 2years were not different whatever the irradiation device, respectively of 96.2% (range, 90.8-100) and 98.1% (range, 94.4-100), P=0.68. Toxicity incidence significantly increased with V5 value>17.2% (56.0 vs. 77.4%, P=0.021). Compared to other SBRT techniques, CK treatments permitted to treat comparable GTV with reduced PTV and V5. Toxicity incidence was less frequent when reducing the V5. CK is particularly attractive in case of multiple courses of lung SBRT or lung reirradiation

Influence of the Hypersensitivity to Low Dose Phenomenon on the Tumor Response to Hypofractionated Stereotactic Body Radiation Therapy.

Stereotactic body radiation therapy (SBRT) has made the hypofractionation of high doses delivered in a few sessions more acceptable. While the benefits of hypofractionated SBRT have been attributed to additional vascular, immune effects, or specific cell deaths, a radiobiological and mechanistic model is still needed. By considering each session of SBRT, the dose is divided into hundreds of minibeams delivering some fractions of Gy. In such a dose range, the hypersensitivity to low dose (HRS) phenomenon can occur. HRS produces a biological effect equivalent to that produced by a dose 5-to-10 times higher. To examine whether HRS could contribute to enhancing radiation effects under SBRT conditions, we exposed tumor cells of different HRS statuses to SBRT. Four human HRS-positive and two HRS-negative tumor cell lines were exposed to different dose delivery modes: a single dose of 0.2 Gy, 2 Gy, 10 × 0.2 Gy, and a single dose of 2 Gy using a non-coplanar isocentric minibeams irradiation mode were delivered. Anti-γH2AX immunofluorescence, assessing DNA double-strand breaks (DSB), was applied. In the HRS-positive cells, the DSB produced by 10 × 0.2 Gy and 2 Gy, delivered by tens of minibeams, appeared to be more severe, and they provided more highly damaged cells than in the HRS-negative cells, suggesting that more severe DSB are induced in the "SBRT modes" conditions when HRS occurs in tumor. Each SBRT session can be viewed as hyperfractionated dose delivery by means of hundreds of low dose minibeams. Under current SBRT conditions (i.e., low dose per minibeam and not using ultra-high dose-rate), the response of HRS-positive tumors to SBRT may be enhanced significantly. Interestingly, similar conclusions were reached with HRS-positive and HRS-negative untransformed fibroblast cell lines, suggesting that the HRS phenomenon may also impact the risk of post-RT tissue overreactions