Local control and radionecrosis of brain metastases from non-small-cell lung cancer treated by hypofractionated stereotactic radiotherapy: Evaluation of predictive factors.

Background: The objective of our study was to report predictive factors of local control (LC) and radionecrosis (RN) of brain metastases (BM) of non-small cell lung carcinoma (NSCLC) treated by multifractionated stereotactic radiotherapy (MF-SRT) according to French recommendations. Method: From 2012 to 2020, 87 patients with 101 BM were retrospectively included. The median age was 63 years (37-85). GTV was defined using contrast-enhanced T1w MRI and was isotropically extended by 2 mm to form PTV. Mean maximum BM diameter was 24.5 mm (10-46). Patients were treated with dynamic arctherapy from May 2012 to February 2016 and then with VMAT. The total prescribed dose was 23.1 Gy prescribed to the encompassing 70% isodose, in 3 fractions. Results: LC rates at 6 months, 1 year and 2 years was 95.7%, 90.7% and 87.9% respectively. In multivariate analysis, high GTV Dmin (HR = 0.822, p = 0.012) was in favor of better LC whereas a large maximum diameter was predictive of poor LC (HR = 1.124, p = 0.02). GTV Dmin of 27.4 Gy was identified as a discriminant threshold of LC. In case of GTV Dmin ≥ 27.4 Gy, LC at 1 year was 95.3% versus 75.1% with GTV Dmin < 27.4 Gy. Cumulative incidence of RN at 6 months, 1 year and 2 years was 6.3%, 15.4% and 18.1%, respectively. In multivariate analysis, only dyslipidemia was predictive of RN (HR = 2.69, p = 0.03). No dosimetric predictive factor of RN was found in our study. Conclusion: MF-SRT (3x7.7 Gy on 70% isodose line, with PTV = GTV + 2 mm; according to French recommendations) of BM from NSCLC gives high LC rates with acceptable RN rate. A GTV Dmin of at least 27.4 Gy could be proposed to optimize dosimetric objectives. No dosimetric predictive factors of RN were found in this study. However, dyslipidemia was identified as a potential predictive factor of RN.

Significant correlation between gross tumor volume (GTV) D98% and local control in multifraction stereotactic radiotherapy (MF-SRT) for unresected brain metastases.

BACKGROUND: Stereotactic radiotherapy (SRT) should be applied with a biologically effective dose with an α/ß of 12 (BED12) ≥ 40 Gy to reach a 1-year local control (LC) ≥ 70%. The aims of this retrospective study were to report a series of 81 unresected large brain metastases treated with Linac-based multifraction SRT according to the ICRU 91 and to identify predictive factors associated with LC. METHODS: Included in this study were the first 81 brain metastases (BM) consecutively treated with Linac-based volumetric modulated arc therapy (VMAT) multifraction SRT from 2017 to 2019. The prescribed dose was 33 Gy for the GTV and 23.1 Gy (70% isodose line) for the PTV in 3 fractions (3f). Mean BM largest diameter and GTV were 25.1 mm and 7.2 cc respectively. Mean follow-up was 10.2 months. RESULTS: LC was 79.7% and 69.7% at 1 and 2 years respectively. Significant predictive factors of LC were GTV D98% (HR = 0.84, CI 95% = 0.75-0.95, p = 0.004) and adenocarcinoma as the histological type (HR = 0.29, CI 95% = 0.09-0.96, p = 0.042) in univariate and multivariate analysis. A threshold of 29 Gy for GTV D98% was significantly correlated to LC (1-year LC = 91.9% for GTV D98% ≥ 29 Gy vs 69.6% for GTV D98% < 29 Gy (p = 0.030)), corresponding to a BED12 = 52.4 Gy. No tumor progression was observed for a BED12 ≥ 53.4 Gy, corresponding to a GTV D98% ≥ 20 Gy /1f and GTV D98% ≥ 29.4 Gy 3f. Median OS was 15 months. Symptomatic radionecrosis occurred in 4.9% of cases. CONCLUSION: The GTV D98% is a strong reproducible significant predictive factor of LC for brain SRT. Dose prescription should lead to a GTV BED12 98% ≥ 52.4-53.4 Gy to significantly improve LC, corresponding to respectively a GTV D98% ≥ 19.7-20 Gy/1f and 29-29.4 Gy/3f.

Stereotactic Radiosurgery for Vestibular Schwannomas: Reducing Toxicity With 11 Gy as the Marginal Prescribed Dose.

BACKGROUND: Stereotactic radiosurgery (SRS) is a common treatment option for vestibular schwannomas. Historically, a dose de-escalation of the marginal prescribed dose from 16 Gy to 12-13 Gy has been done to limit toxicity without reducing local control (LC). We aimed to retrospectively report outcomes of Linac-based SRS for vestibular schwannomas treated with different doses. METHODS: Included in the study were 97 stage 1 (1%), 2 (56%), 3 (21.5%), and 4 (21.5%) vestibular schwannomas treated with Linac-based (Novalis®) SRS from 1995 to 2019. No margin was added to the GTV to create the PTV. The median marginal prescribed dose was 14 Gy (range: 12-16 Gy) before 2006 and then 11 Gy for all patients (61 pts). Mean tumor volume was 1.96 cm3, i.e., about 1.6 cm in diameter. Mean follow-up was 8.2 years. RESULTS: Following SRS, LC at 3, 5, and 10 years was 100%, 98.4%, and 95.6%, respectively [100% for those with ≤ 13 Gy as the marginal prescribed dose (NS)]. Toxicity to the trigeminal nerve was reported in 7.2% of cases (3.3% and 0% for transient and permanent toxicity for 11 Gy). The marginal prescribed dose was the only significant predictive factor in univariate and multivariate analysis (HR = 1.77, 95% CI = 1.07-3.10, p = 0.028). Toxicity to the facial nerve was reported in 6.2% of cases. The marginal prescribed dose was again the only significant predictive factor in univariate and multivariate analysis (HR = 1.31, 95% CI = 0.77-2.23, p = 0.049). CONCLUSION: Linac-based SRS for stages 1-3 vestibular schwannomas provides excellent outcomes: a 10-year LC rate of over 95%, with a permanent facial or trigeminal toxicity rate of under 5%. A marginal prescribed dose of 11 Gy seems to decrease nerve toxicity and facial toxicity in particular, without reducing LC. Prospective studies with longer follow-up are needed.

Significant Correlation Between Overall Survival and Mean Lung Dose in Lung Stereotactic Body Radiation Therapy (SBRT).

BACKGROUND: After stereotactic body radiation therapy (SBRT) for medically inoperable stage I non-small-cell lung cancer (NSCLC), more patients die of comorbidities, particularly severe pulmonary insufficiency, than of tumor progression. The aim of this study was to evaluate correlation between lung biologically effective dose (BED) with an α/ß ratio of 3 Gy (BED3) and overall survival (OS) for these patients. METHODS: From 2012 to 2017, we have developed a prospectively updated institutional database for all first 100 consecutively treated patients with inoperable Stage 1 (T1T2N0M0) NSCLC. All SBRT were conducted on a Novalis Tx® LINAC with two coplanar dynamic conformal arcs (84%) or with coplanar volumetric modulated arc therapy (VMAT) (16%). Mean GTV and PTV were 8.6 cc and 50.8 cc, respectively. The marginal dose prescribed to the PTV was the 80% isodose line (IDL), i.e., 54 Gy in 3 fractions for 76 patients (BED10 = 126 Gy) and 50 Gy in 5 fractions for 24 patients (BED10 = 83.3 Gy). Pulmonary heterogeneity has been taken into account by using Monte Carlo or AAA algorithms. Median follow-up was 25 months. RESULTS: At 1, 2, 3 and 5 years, local control (LC) was respectively 100, 98.2, 98.2, and 77.7%, and OS was respectively 83, 71.2, 58.1, and 33.2% (median OS was 49 months). Significant OS prognostic factors in univariate and multivariate analysis were mean lung BED3 (HR = 1.14, p = 0.01) and PTV volume (HR = 1.01, p = 0.004). A mean lung BED3 ≤ 5 Gy was significantly associated with a doubling of median OS from 29 months to more than 60 months (not achieved, p = 0.0068). For patients with a forced expiratory volume in 1 second (FEV1) ≤ 40%, a mean lung BED3 ≤ 4 Gy was significantly associated with a doubling of median OS from 23 to 46 months (p = 0.019). CONCLUSION: Mean lung BED3 is strongly and significantly associated with OS in SBRT for inoperable Stage I NSCLC. For all treated patients, a mean lung BED3 ≤ 5 Gy lead to a doubling of median OS. This threshold value should be reduced to 4 Gy for patients with FEV1 ≤ 40%.