Predictors Of Radiation Necrosis Research Articles

Dose-Volume Tolerance of the Brain and Predictors of Radiation Necrosis After 3-Fraction Radiosurgery for Brain Metastases: A Large Single-Institutional Analysis

Stereotactic radiosurgery (SRS) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side effect of SRS, but the dose constraints especially for fractionated SRS remain poorly defined. We assessed the risk of RN after 3-fraction SRS with a goal to identify specific dose-volume constraints associated with grade 3 or higher RN (G3RN). A single-institutional retrospective review of patients treated with 3-fraction SRS was performed. The primary endpoint was G3RN, which was defined as severe symptoms with evidence of necrosis on magnetic resonance imaging with perfusion and/or biopsy confirmation. Tissue volume around each target lesion was contoured, and volumetric doses per lesion were recorded. Logistic regression models were used to estimate the relationship between RN and each volumetric dose, and normal tissue complication probability modeling was performed using a modified Lyman-Kutcher-Burman model. From 2015 to 2021, 434 patients underwent 539 courses of linear accelerator-based SRS; 2518 lesions were treated. Median SRS dose was 24 Gy. Median follow-up after SRS was 7.9 months, and the median overall survival was 9 months. A total of 93 patients (17.2%) and 123 lesions (4.9%) developed any RN. Forty-two patients (7.8%) and 57 lesions (2.3%) developed G3RN. On logistic regression, V20 and V23 were best predictors of any grade RN and G3RN, respectively, with cutoff values of 4 cc, 10 cc, and 20 cc associated with <5%, <7.5%, and <10% risk of any RN, respectively, and V23 < 15 cc associated with <5% risk of G3RN. With constrained optimization of the normal tissue complication probability Lyman-Kutcher-Burman model for G3RN, we obtained a TD50 (uniform dose resulting in a 50% complication risk) of 31.4 Gy (95% CI, 27.8-35.1 Gy). In patients receiving 3-fraction SRS, G3RN was seen in 7.8% of patients, and 2.3% of the lesions were treated. V20 and V23 were the most robust dosimetric parameters associated with RN. Further studies evaluating the outcomes and RN in patients treated with fractionated SRS compared with single-fraction SRS are warranted.

RE-IRRADIATION FOR RECURRENT HIGH-GRADE GLIOMA: AN ANALYSIS OF PROGNOSTIC FACTORS FOR SURVIVAL AND PREDICTORS OF RADIATION NECROSIS

Abstract Recurrent high-grade glioma (rHGG) is a heterogeneous population, and the ideal patient selection for reirradiation (re-RT) has yet to be established. This study aims to identify prognostic factors for rHGG patients treated with re-RT. METHODS: We retrospectively reviewed consecutive adults with rHGG who underwent re-RT from 2009-2020 from our institutional database. The primary objective was overall survival (OS). The secondary outcomes included prognostic factors for early death (&amp;lt;6 months after re-RT) and predictors of radiation necrosis (RN). RESULTS: For the 79 patients identified, the median OS after re-RT was 9.9 months (95% CI 8.3-11.6). On multivariate analyses (MVA), re-resection at progression (HR=0.56, p=0.027), interval from primary treatment to first progression ≥16.3 months (HR=0.61, p=0.034), interval from primary treatment to re-RT ≥23.9 months (HR=0.35, p&amp;lt;0.001), and re-RT PTV volume &amp;lt;112 cc (HR=0.27, p&amp;lt;0.001) were prognostic for improved OS. Patients who had unmethylated-MGMT tumours (OR=12.4, p=0.034), ≥3 prior systemic treatment lines (OR=29.1, p=0.22), interval to re-RT &amp;lt;23.9 months (OR=9.0, p=0.039), and re-RT PTV volume ≥112 cc (OR=17.8, p=0.003) were more likely to survive &amp;lt;6 months. The cumulative incidence of RN was 11.4% (95% CI 4.3-18.5) at 12 months. Concurrent bevacizumab use (HR&amp;lt;0.001, p&amp;lt;0.001) and cumulative equivalent dose in 2 Gy fractions (cEQD2, a/b=2) &amp;lt;99 Gy2 (HR&amp;lt;0.001, p&amp;lt;0.001) were independent protective factors against RN. CONCLUSIONS: We observe favorable OS rates following re-RT and identified prognostic factors, including methylation status, that can assist in patient selection and clinical trial design. Concurrent use of bevacizumab and cEQD2 &amp;lt;99 Gy2 mitigates the risk of RN.

Re-irradiation for recurrent high-grade glioma: an analysis of prognostic factors for survival and predictors of radiation necrosis.

Recurrent high-grade glioma (rHGG) is a heterogeneous population, and the ideal patient selection for re-irradiation (re-RT) has yet to be established. This study aims to identify prognostic factors for rHGG patients treated with re-RT. We retrospectively reviewed consecutive adults with rHGG who underwent re-RT from 2009 to 2020 from our institutional database. The primary objective was overall survival (OS). Secondary endpoints included prognostic factors for early death (< 6months after re-RT) and predictors of radiation necrosis (RN). For the 79 patients identified, the median OS after re-RT was 9.9months (95% CI 8.3-11.6). On multivariate analyses, re-resection at progression (HR 0.56, p = 0.027), interval from primary treatment to first progression ≥ 16.3months (HR 0.61, p = 0.034), interval from primary treatment to re-RT ≥ 23.9months (HR 0.35, p < 0.001), and re-RT PTV volume < 112cc (HR 0.27, p < 0.001) were prognostic for improved OS. Patients who had unmethylated-MGMT tumours (OR 12.4, p = 0.034), ≥ 3 prior systemic treatment lines (OR 29.1, p = 0.022), interval to re-RT < 23.9months (OR 9.0, p = 0.039), and re-RT PTV volume ≥ 112cc (OR 17.8, p = 0.003) were more likely to die within 6months of re-RT. The cumulative incidence of RN was 11.4% (95% CI 4.3-18.5) at 12months. Concurrent bevacizumab use (HR < 0.001, p < 0.001) and cumulative equivalent dose in 2Gy fractions (EQD2, α/β = 2) < 99 Gy2 (HR < 0.001, p < 0.001) were independent protective factors against RN. Re-RT allowed for less corticosteroid dependency. Sixty-six percent of failures after re-RTwere in-field. We observe favorable OS rates following re-RT and identified prognostic factors, including methylation status, that can assist in patient selection and clinical trial design. Concurrent use of bevacizumab mitigated the risk of RN.

Predictors of Radiation Necrosis and Dose/Volume Tolerance of the Brain after Three-Fraction Radiosurgery for Brain Metastases: A Large Single-Institutional Analysis

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side-effect of SRS but the dose constraints are poorly defined. FSRT can decrease risk of RN over SRS while maintaining or improving high rates of overall survival (OS). We assessed the survival and risk of RN after FSRT with a goal to identify specific dose/volume constraints associated with grade 3 or higher RN using NTCP modeling. <h3>Materials/Methods</h3> A single-institutional retrospective review of patients treated with 3-fraction FSRT from 2015 to 2020 was performed. Tissue volume (brain + target) around each target lesion was contoured in a consistent manner and volumetric doses per lesion were recorded. RN was defined using biopsy or MRI with perfusion as available and graded using CTCAE version 5.0. Our primary endpoint was grade 3 or higher RN. All statistical analyses were performed using statistical software. <h3>Results</h3> From 2015 to 2020, a total of 439 patients underwent 509 courses of 3-fraction Linac-based FSRT, treating a total of 2394 metastatic lesions (range 1-71, mean = 4.7 and median = 3 lesions per course). 61 patients had ≥10 and 31 patients had ≥15 lesions treated per course. Median RT dose per fraction was 8 Gy (range 5-9 Gy). 11.8% patients received prior whole brain radiation (WBRT). Median follow-up after RT was 8 months (IQR 3-18m). A total of 64 patients (78 lesions) developed RN with 17, 17, 29 and 1 patients developing grade 1, 2, 3 and 4 RN respectively. Grade 3 or higher RN was observed in 5.9% patients. On per lesion analysis, rate of any RN and grade 3 RN was 3.2% and 1.5% respectively. Median time to RN was 11.3m (range 0.7 – 38.4). Of 30 patients with grade 3 or higher RN, 7 (23%) received prior WBRT, 19 (63%) received post-op FSRT to the cavity and 1 (3%) received pre-op FSRT. Most of these patients were managed by steroids, while 25 underwent resection and 6 received bevacizumab. Tissue volume receiving 20 Gy (V20) of <20cc or >20 cc was associated with 2.5% and 10.2% risk of RN respectively, while a V23 of <20 cc or >20 cc was associated with 2.3% vs 12.1% risk of grade 3 or higher RN. Mean V20 in patients who developed Grade 3 or higher RN was statistically higher than the entire cohort (36.9cc vs 14.1cc, p=0.002). Median OS after RT was 10m (1yr and 2yr OS of 45.8% and 30.4%, respectively) while patients who developed RN survived longer compared to rest of the cohort (32m vs 8m, p <0.001). Patients with 15 or more lesions treated per course had similar survival compared to rest of the cohort (8m vs 10m, p = 0.136), after excluding those who received prior WBRT. <h3>Conclusion</h3> In patients receiving 3 fraction FSRT, grade 3 or higher RN was seen in 5.9% patients and 1.5% lesions treated. Risk of RN was significantly lower in patients with V23 of <20 cc. Further studies evaluating the outcomes and RN in patients treated with FSRT compared to SRS or hippocampal avoidance WBRT are warranted.

Predictors of Radiation Necrosis in Long-term Survivors of Stereotactic Radiosurgery for Brain Metastases

Predictors of Radiation Necrosis in Long-term Survivors of Stereotactic Radiosurgery for Brain Metastases

Necrosis following radiotherapy for carcinoma of the pinna

Purpose: Radiation therapy is often the preferred modality of treatment for carcinoma of the pinna because it avoids the cosmetic defect of surgery. However, radiation oncologists are sometimes reluctant to irradiate the ear because of the risk of subsequent necrosis. The goal of this study was to establish the long-term disease control and necrosis rates following irradiation of the external ear.Methods and Materials: A retrospective analysis was undertaken of 138 courses of curative radiotherapy given to 128 patients for biopsy-proven basal (70 courses), squamous (62 courses), or mixed (6 courses) tumors of the pinna between January 1, 1982, and December 31, 1991, at the Kingston Regional Cancer Center.Results: The median age of the patients was 73 (range 43–94) and the median size of the tumors was 12 mm (range 3–50 mm). Treatment was given using orthovoltage X rays (79) or electron (59). The most common dose prescription was 35 Gy/5 fractions; total doses ranged from 17.50 to 64 Gy. The median follow-up is 58 months (range 6–149). The actuarial 5-year local control rate is 93%; the actuarial necrosis rate at 5 years is 13%. Most necroses healed with conservative management; only two patients required surgery for necrosis. We analyzed the following factors as possible predictors of radiation necrosis; patient age, size of lesion, histology, fraction size total dose, overall time, and beam energy. Only daily fraction sizes > 6 Gy (p = 0.0093) and treatment times < 5 days (p = 0.0053) were significantly associated with an increased risk of necrosis. Conclusion: To reduce the risk of necrosis, radiation therapy for external ear cancer should be given using protracted fractionation.