Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy

Background The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT. Methods Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed. Results The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions. Conclusions Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.

Simultaneous stereotactic radiosurgery of multiple brain metastases using single-isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

Background Single-isocenter dynamic conformal arc (SIDCA) therapy is a technically efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of linear accelerator (LINAC) based SRS with SIDCA for patients with multiple brain metastases. Methods All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial were included. The patients were irradiated with a dedicated planning tool for multiple brain metastases using a LINAC with a 5 mm multileaf collimator. Follow-up was performed every 3 months, including clinical and radiological examination with cranial magnetic resonance imaging (MRI). These early data were analyzed using descriptive statistics and the Kaplan–Meier method. Results A total of 65 patients with 254 lesions (range 2–12) were included in this analysis. Median beam-on time was 23 min. The median follow-up at the time of analysis was 13 months (95% CI 11.1–14.9). Median overall survival and median intracranial progression-free survival was 15 months (95% CI 7.7–22.3) and 7 months (95% CI 3.9–10.0), respectively. Intracranial and local control after 1 year was 64.6 and 97.5%, respectively. During follow-up, CTCAE grade I adverse effects (AE) were experienced by 29 patients (44.6%; 18 of them therapy related, 27.7%), CTCAE grade II AEs by four patients (6.2%; one of them therapy related, 1.5%), and CTCAE grade III by three patients (4.6%; none of them therapy related). Two lesions (0.8%) in two patients (3.1%) were histopathologically proven to be radiation necrosis. Conclusion Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple brain metastases.

Dosimetric study between a single isocenter dynamic conformal arc therapy technique and Gamma Knife radiosurgery for multiple brain metastases treatment: impact of target volume geometrical characteristics

Purpose To compare linac-based mono-isocentric radiosurgery with Brainlab Elements Multiple Brain Mets (MBM) SRS and the Gamma Knife using a specific statistical method and to analyze the dosimetric impact of the target volume geometric characteristics. A dose fall-off analysis allowed to evaluate the Gradient Index relevancy for the dose spillage characterization. Material and methods Treatments were planned on twenty patients with three to nine brain metastases with MBM 2.0 and GammaPlan 11.0. Ninety-five metastases ranging from 0.02 to 9.61 cc were included. Paddick Index (PI), Gradient Index (GI), dose fall-off, volume of healthy brain receiving more than 12 Gy (V12Gy) and DVH were used for the plan comparison according to target volume, major axis diameter and Sphericity Index (SI). The multivariate regression approach allowed to analyze the impact of each geometric characteristic keeping all the others unchanged. A parallel study was led to evaluate the impact of the isodose line (IDL) prescription on the MBM plan quality. Results For mono-isocentric linac-based radiosurgery, the IDL around 70–75% was the best compromise found. For both techniques, the GI and the dose fall-off decreased with the target volume. In comparison, PI was slightly improved with MBM for targets < 1 cc or SI > 0.78. GI was improved with GP for targets < 2.5 cc. The V12Gy was higher with MBM for lesions > 0.4 cc or SI < 0.84 and exceeded 10 cc for targets > 5 cc against 6.5 cc with GP. The presence of OAR close to the PTV had no impact on the dose fall off values. The dose fall-off was higher for volumes < 3.8 cc with GP which had the sharpest dose fall-off in the infero-superior direction up to 30%/mm. The mean beam-on time was 94 min with GP against 13 min with MBM. Conclusions The dose fall-off and the V12Gy were more relevant indicators than the GI for the low dose spillage assessment. Both evaluated techniques have comparable plan qualities with a slightly improved selectivity with MBM for smaller lesions but with a healthy tissues sparing slightly favorable to GP at the expense of a considerably longer irradiation time. However, a higher healthy tissue exposure must be considered for large volumes in MBM plans.

Simultaneous stereotactic radiosurgery of multiple brain metastases using single isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

Background Single-isocenter dynamic conformal arc (SIDCA) therapy is an efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of SRS with SIDCA for patients with multiple brain metastases.Methods All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial, were included. The patients were irradiated using a VersaHD® linear accelerator (LINAC) from Elekta (Stockholm, Sweden). Follow-up was performed every three months, including a clinical and radiological examination with cranial magnetic resonance imaging (MRI). The data were analyzed using descriptive statistics and the Kaplan-Meier method.Results 65 patients with 254 lesions (range 2–12) were included in this analysis. Median beam on time was 23 minutes. The median follow-up at the time of analysis was 13 months (95% CI 11.1–14.9). Median overall survival and median progression-free survival was 15 months (95% CI 7.7–22.3) and 18 months (95% CI 11.1–24.9), respectively. Intracranial and local control after 6 months was 73.0% and 97.5%, respectively. During follow-up, CTCAE grade 1 adverse effects (AE) were experienced by 29 (44.6%) patients (18 of them therapy-related (27.7%)), CTCAE grade 2 AEs by 4 (6.2%) patients (one of them therapy-related (1.5%)) and CTCAE grade 3 by 3 patients (4.6%) (none of them therapy-related). 2 lesions (0.8%) in 2 patients (3.1%) were proven as radiation necrosis. Conclusions Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple metastases.

Stereotactic radiotherapy for small and very small tumours (≤1 to ≤3 cc): evaluation of the influence of volumetric-modulated arc therapy in comparison to dynamic conformal arc therapy and 3D conformal radiotherapy as a function of flattened and unflattened beam models

Purpose: The objective of this article is to evaluate the dosimetric efficacy of volumetric modulated arc therapy (VMAT) in comparison to dynamic conformal arc therapy (DCAT) and 3D conformal radiotherapy (3DCRT) for very small volume (≤1 cc) and small volume (≤3 cc) tumours for flattened (FF) and unflattened (FFF) 6 MV beams. Materials and methods: A total of 21 patients who were treated with single-fraction stereotactic radiosurgery, using either VMAT, DCAT or 3DCRT, were included in this study. The volume categorisation was seven patients each in <1, 1–2 and 2–3 cc volume. The treatment was planned with 6 MV FF and FFF beams using three different techniques: VMAT/Rapid Arc (RA) (RA_FF and RA_FFF), dynamic conformal arc therapy (DCA_FF and DCA_FFF) and 3DCRT (Static_FF and Static_FFF). Plans were evaluated for target coverage (V100%), conformity index, homogeneity index, dose gradient for 50% dose fall-off, total MU and MU/dose ratio [intensity-modulated radiotherapy (IMRT) factor], normal brain receiving >12 Gy dose, dose to the organ at risk (OAR), beam ON time and dose received by 12 cc of the brain. Result: The average target coverage for all plans, all tumour volumes (TVs) and delivery techniques is 96·4 ± 4·5 (range 95·7 ± 6·1–97·5 ± 2·9%). The conformity index averaged over all volume ranges <1, 2, 3 cc> varies between 0·55 ± 0·08 and 0·68 ± 0·04 with minimum and maximum being exhibited by DCA_FFF for 1 cc and Static_FFF/RA_FFF for 3 cc tumours, respectively. Mean IMRT factor averaged over all volume ranges for RA_FF, DCA_FF and Static_FF are 3·5 ± 0·8, 2·0 ± 0·2 and 2·0 ± 0·2, respectively; 50% dose fall-off gradient varies in the range of 0·33–0·42, 0·35–0·40 and 0·38–0·45 for 1, 2 and 3 cc tumours, respectively. Conclusion: This study establishes the equivalence between the FF and FFF beam models and different delivery techniques for stereotactic radiosurgery in small TVs in the range of ≤1 to ≤3 cc. Dose conformity, heterogeneity, dose fall-off characteristics and OAR doses show no or very little variation. FFF could offer only limited time advantage due to excess dose rate over an FF beam.